[Regional Differences in the Care of Patients with Neovascular Age-Related Macular Degeneration, Based on the Non-Interventional OCEAN Study].

PubMed

Ziemssen, F; Hufenbach, U; Wiedon, A; Scheffler, M; Bertelmann, T

2016-12-01

Background: The main cause of blindness in the elderly in Germany is neovascular age-related macular degeneration (nAMD). In the non-interventional OCEAN study, data were prospectively collected on the routine clinical care of patients treated with the drug ranibizumab. Patients: As part of an interim analysis within the ongoing study (NCT02194803), stratification was performed by the 17 regions of the German associations of panel physicians and by areas of different population density. Only data were analysed for patients for whom the first treatment with ranibizumab was documented. Results: A total of 5,606 patients were documented. The present manuscript reviews 2,658 treatment-naive patients with nAMD, documented by 324 ophthalmologists. Most patients receiving an intravitreal injection were female (60 %). The average patient was aged 77.7 ± 8.2 years at study start. The great majority of patients had statutory health insurance (91 %). At baseline, fluorescein angiography (FLA) was performed for 72 % of patients, while optical coherence tomography (OCT) was carried out for 76 %. A combination of both was performed for 54 % of patients, varying regionally from 26 % (Saxony-Anhalt) to 100 % (Berlin). The average waiting time between the first examination and the first injection was 20.0 ± 18.5 days. With different statistical models (ANOVA adjusted, with/without interactions), significant effects on treatment delay were found for district type (population density), federal state and type of specialist. Conclusion: No major regional differences were observed in the demographic characteristics of the patient population. The main regional disparities in the care of nAMD patients were in the application of diagnostic methods and the waiting times between the first examination and the first drug administration. The regional variations in treatment delays could clearly influence the risk of worse functional outcome. Georg Thieme Verlag KG Stuttgart · New York.

The Antarctic Master Directory -- the Electronic Card Catalog of Antarctic Data

NASA Astrophysics Data System (ADS)

Scharfen, G.; Bauer, R.

2003-12-01

The Antarctic Master Directory (AMD) is a Web-based, searchable record of thousands of Antarctic data descriptions. These data descriptions contain information about what data were collected, where they were collected, when they were collected, who the scientists are, who the point of contact is, how to get the data, and information about the format of the data and what documentation and bibliographic information exists. With this basic descriptive information about content and access for thousands of Antarctic scientific data sets, the AMD is a resource for scientists to advertise the data they have collected and to search for data they need. The AMD has been created by more than twenty nations which conduct research in the Antarctic under the auspices of the Antarctic Treaty. It is a part of the International Directory Network/Global Change Master Directory (IDN/GCMD). Using the AMD is easy. Users can search on subject matter key words, data types, geographic place-names, temporal or spatial ranges, or conduct free-text searches. To search the AMD go to: http://gcmd.nasa.gov/Data/portals/amd/. Contributing your own data descriptions for Antarctic data that you have collected is also easy. Scientists can start by submitting a short data description first (as a placeholder in the AMD, and to satisfy National Science Foundation (NSF) reporting requirements), and then add to, modify or update their record whenever it is appropriate. An easy to use on-line tool and a simple tutorial are available at: http://nsidc.org/usadcc. With NSF Office of Polar Programs (OPP) funding, the National Snow and Ice Data Center (NSIDC) operates the U.S. Antarctic Data Coordination Center (USADCC), partly to assist scientists in using and contributing to the AMD. The USADCC website is at http://nsidc.org/usadcc.

Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables.

PubMed

Seddon, Johanna M; Reynolds, Robyn; Maller, Julian; Fagerness, Jesen A; Daly, Mark J; Rosner, Bernard

2009-05-01

The joint effects of genetic, ocular, and environmental variables were evaluated and predictive models for prevalence and incidence of AMD were assessed. Participants in the multicenter Age-Related Eye Disease Study (AREDS) were included in a prospective evaluation of 1446 individuals, of which 279 progressed to advanced AMD (geographic atrophy or neovascular disease) and 1167 did not progress during 6.3 years of follow-up. For prevalent AMD, 509 advanced cases were compared with 222 controls. Covariates for the incidence analysis included age, sex, education, smoking, body mass index (BMI), baseline AMD grade, and the AREDS vitamin-mineral treatment assignment. DNA specimens were evaluated for six variants in five genes related to AMD. Unconditional logistic regression analyses were performed for prevalent and incident advanced AMD. An algorithm was developed and receiver operating characteristic curves and C statistics were calculated to assess the predictive ability of risk scores to discriminate progressors from nonprogressors. All genetic polymorphisms were independently related to prevalence of advanced AMD, controlling for genetic factors, smoking, BMI, and AREDS treatment. Multivariate odds ratios (ORs) were 3.5 (95% confidence interval [CI], 1.7-7.1) for CFH Y402H; 3.7 (95% CI, 1.6-8.4) for CFH rs1410996; 25.4 (95% CI, 8.6-75.1) for LOC387715 A69S (ARMS2); 0.3 (95% CI, 0.1-0.7) for C2 E318D; 0.3 (95% CI, 0.1-0.5) for CFB; and 3.6 (95% CI, 1.4-9.4) for C3 R102G, comparing the homozygous risk/protective genotypes to the referent genotypes. For incident AMD, all these variants except CFB were significantly related to progression to advanced AMD, after controlling for baseline AMD grade and other factors, with ORs from 1.8 to 4.0 for presence of two risk alleles and 0.4 for the protective allele. An interaction was seen between CFH402H and treatment, after controlling for all genotypes. Smoking was independently related to AMD, with a multiplicative joint effect with genotype on AMD risk. The C statistic for the full model with all variables was 0.831 for progression to advanced AMD. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power.

Dactinomycin and Vincristine Toxicity in the Treatment of Childhood Cancer: A Retrospective Study from the Children’s Oncology Group

PubMed Central

Langholz, Bryan; Skolnik, Jeffrey M.; Barrett, Jeffrey S.; Renbarger, Jamie; Seibel, Nita L.; Zajicek, Anne; Arndt, Carola A.S.

2011-01-01

Background Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking. Methods Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical modeling was used to account for differences in AE data collection across studies, develop rate models for grade 3/4 CTCAE v3 hepatic- (AMD) and neuro- (AMD) toxicity, assess variation in toxicity rates over age and other factors, and predict toxicity risk under current dosing guidelines. Results For the same dose/body size, AMD toxicity rates were higher in patients <1 year than older patients and VCR toxicity rates increased with age. The statistical model provided estimates for AMD and VCR toxicity risk under current dosing schedules and indicated that patients of smaller body size were at lower risk of VCR toxicity than larger patients of the same age. The rate of AMD toxicity was highest early in treatment and was lower in patients who tolerated initial AMD without toxicity. Conclusion The observed decrease in AMD toxicity rate with cumulative dose may indicate sensitivity in a subgroup of patients while the observed increase in VCR toxicity risk with age may indicate changing sensitivity to VCR. Current dosing practices result in a fairly uniform toxicity profile within age group. However, PK/PD studies should be done to provide further provide further information on best dosing guidelines. PMID:21671362

Six-Year Incidence of Age-Related Macular Degeneration in Asian Malays: The Singapore Malay Eye Study.

PubMed

Cheung, Chui Ming Gemmy; Ong, Peng Guan; Neelam, Kumari; Tan, Pok Chien; Shi, Yuan; Mitchell, Paul; Wang, Jie Jin; Sabanayagam, Charumathi; Cheng, Ching-Yu; Wong, Tien Yin

2017-09-01

To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians. Prospective, population cohort study. The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part. Fundus photographs were graded using the Wisconsin AMD grading system. Incidence of early and late AMD. Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%). This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Cloning and analysis of the positively acting regulatory gene amdR from Aspergillus nidulans.

PubMed Central

Andrianopoulos, A; Hynes, M J

1988-01-01

The positively acting regulatory gene amdR of Aspergillus nidulans coordinately regulates the expression of four unlinked structural genes involved in acetamide (amdS), omega amino acid (gatA and gabA), and lactam (lamA) catabolism. By the use of DNA-mediated transformation of A. nidulans, the amdR regulatory gene was cloned from a genomic cosmid library. Southern blot analysis of DNA from various loss-of-function amdR mutants revealed the presence of four detectable DNA rearrangements, including a deletion, an insertion, and a translocation. No detectable DNA rearrangements were found in several constitutive amdRc mutants. Analysis of the fate of amdR-bearing plasmids in transformants showed that 10 to 20% of the transformation events were homologous integrations or gene conversions, and this phenomenon was exploited in developing a strategy by which amdRc and amdR- alleles can be readily cloned and analyzed. Examination of the transcription of amdR by Northern blot (RNA blot) analysis revealed the presence of two mRNAs (2.7 and 1.8 kilobases) which were constitutively synthesized at a very low level. In addition, amdR transcription did not appear to depend on the presence of a functional amdR product nor was it altered in amdRc mutants. The dosage effects of multiple copies of amdR in transformants were examined, and it was shown that such transformants exhibited stronger growth than did the wild type on acetamide and pyrrolidinone media, indicating increased expression of the amdS and lamA genes, respectively. These results were used to formulate a model for amdR-mediated regulation of gene expression in which the low constitutive level of amdR product sets the upper limits of basal and induced transcription of the structural genes. Multiple copies of 5' sequences from the amdS gene can result in reduced growth on substrates whose utilization is dependent on amdR-controlled genes. This has been attributed to titration of limiting amdR gene product. Strong support for this proposal was obtained by showing that multiple copies of the amdR gene can reverse this phenomenon (antititration). Images PMID:3062382

Risk assessment model for development of advanced age-related macular degeneration.

PubMed

Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

2011-12-01

To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

Complement pathway biomarkers and age-related macular degeneration

PubMed Central

Gemenetzi, M; Lotery, A J

2016-01-01

In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

Ground-state properties of neutron-rich Mg isotopes

NASA Astrophysics Data System (ADS)

Watanabe, S.; Minomo, K.; Shimada, M.; Tagami, S.; Kimura, M.; Takechi, M.; Fukuda, M.; Nishimura, D.; Suzuki, T.; Matsumoto, T.; Shimizu, Y. R.; Yahiro, M.

2014-04-01

We analyze recently measured total reaction cross sections for 24-38Mg isotopes incident on 12C targets at 240 MeV/nucleon by using the folding model and antisymmetrized molecular dynamics (AMD). The folding model well reproduces the measured reaction cross sections, when the projectile densities are evaluated by the deformed Woods-Saxon (def-WS) model with AMD deformation. Matter radii of 24-38Mg are then deduced from the measured reaction cross sections by fine tuning the parameters of the def-WS model. The deduced matter radii are largely enhanced by nuclear deformation. Fully microscopic AMD calculations with no free parameter well reproduce the deduced matter radii for 24-36Mg, but still considerably underestimate them for 37,38Mg. The large matter radii suggest that 37,38Mg are candidates for deformed halo nucleus. AMD also reproduces other existing measured ground-state properties (spin parity, total binding energy, and one-neutron separation energy) of Mg isotopes. Neutron-number (N) dependence of deformation parameter is predicted by AMD. Large deformation is seen from 31Mg with N =19 to a drip-line nucleus 40Mg with N =28, indicating that both the N =20 and 28 magicities disappear. N dependence of neutron skin thickness is also predicted by AMD.

Modeling dynamic exchange of gaseous elemental mercury at polar sunrise.

PubMed

Dastoor, Ashu P; Davignon, Didier; Theys, Nicolas; Van Roozendael, Michel; Steffen, Alexandra; Ariya, Parisa A

2008-07-15

At polar sunrise, gaseous elemental mercury (GEM) undergoes an exceptional dynamic exchange in the air and at the snow surface during which GEM can be rapidly removed from the atmosphere (the so-called atmospheric mercury depletion events (AMDEs)) as well as re-emitted from the snow within a few hours to days in the Polar Regions. Although high concentrations of total mercury in snow following AMDEs is well documented, there is very little data available on the redox transformation processes of mercury in the snow and the fluxes of mercury at the air/snow interface. Therefore, the net gain of mercury in the Polar Regions as a result of AMDEs is still an open question. We developed a new version of the global mercury model, GRAHM, which includes for the first time bidirectional surface exchange of GEM in Polar Regions in spring and summer by developing schemes for mercury halogen oxidation, deposition, and re-emission. Also for the first time, GOME satellite data-derived boundary layer concentrations of BrO have been used in a global mercury model for representation of halogen mercury chemistry. Comparison of model simulated and measured atmospheric concentrations of GEM at Alert, Canada, for 3 years (2002-2004) shows the model's capability in simulating the rapid cycling of mercury during and after AMDEs. Brooks et al. (1) measured mercury deposition, reemission, and net surface gain fluxes of mercury at Barrow, AK, during an intensive measurement campaign for a 2 week period in spring (March 25 to April 7, 2003). They reported 1.7, 1.0 +/- 0.2, and 0.7 +/- 0.2 microg m(-2) deposition, re-emission, and net surface gain, respectively. Using the optimal configuration of the model, we estimated 1.8 microg m(-2) deposition, 1.0 microg m(-2) re-emission, and 0.8 microg m(-2) net surface gain of mercury for the same time period at Barrow. The estimated net annual accumulation of mercury within the Arctic Circle north of 66.5 degrees is approximately 174 t with +/-7 t of interannual variability for 2002-2004 using the optimal configuration. We estimated the uncertainty of the model results to the Hg/Br reaction rate coefficient to be approximately 6%. Springtime is clearly demonstrated as the most active period of mercury exchanges and net surface gain (approximately 46% of annual accumulation) in the Arctic.

Risk factors for exudative age-related macular degeneration in a large French case-control study.

PubMed

Zerbib, Jennyfer; Delcourt, Cécile; Puche, Nathalie; Querques, Giuseppe; Cohen, Salomon Yves; Sahel, José; Korobelnik, Jean-François; Le Goff, Mélanie; Souied, Eric H

2014-06-01

The purpose of the CAP (Creteil AMD PHRC-funded) Study was to analyze risk factors of exudative age-related macular degeneration (AMD) in a large French case-control population. One thousand and twenty-four patients with exudative AMD and 275 controls were recruited. Information about lifestyle, medical history, and dietary intake were collected. Associations of risk factors were estimated using logistic regression. After multivariate adjustment, CFH Y402H and ARMS2 A69S polymorphisms were associated with very high risk for exudative AMD (OR = 6.21 and OR = 11.7, respectively, p < 0.0001). Risk for exudative AMD was increased in current smokers (OR = 3.79, p = 0.0003) and former smokers having quitted since less than 20 years ago (OR = 2.30, p = 0.002), but not in former smokers having quitted since 20 years or more ago (OR = 0.81, p = 0.43). Heavy smokers (at least 25 pack-years) were particularly at risk (OR = 3.61, p < 0.0001). Use of cooking oils rich in omega 3 fatty acids was significantly associated with a reduced risk of exudative AMD (OR = 0.55, 95 % CI: 0.36-0.84, p = 0.006), as well as a high consumption of fruits (OR = 0.60, 95 % CI: 0.37-0.98, p = 0.04), but not the consumption of fish, vegetables or oils rich in omega 6. High waist circumference was associated with increased risk for exudative AMD (OR = 2.53, p < 0.0001), but not hypercholesterolemia, hypertension, or body mass index. The CAP Study confirms major genetic risk factors for exudative AMD. It further documents the high risk in heavy smokers and the long persistence of risk after smoking cessation, and the associations with waist circumference and fruit consumption. Furthermore, we observed an inverse correlation between AMD and cooking oils harboring a beneficial omega-3 fatty acid profile.

JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

PubMed

Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

2013-02-05

Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration.

PubMed

Rojas-Fernandez, Carlos H; Tyber, Kevin

2017-03-01

To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

Minimum-dissipation scalar transport model for large-eddy simulation of turbulent flows

NASA Astrophysics Data System (ADS)

Abkar, Mahdi; Bae, Hyun J.; Moin, Parviz

2016-08-01

Minimum-dissipation models are a simple alternative to the Smagorinsky-type approaches to parametrize the subfilter turbulent fluxes in large-eddy simulation. A recently derived model of this type for subfilter stress tensor is the anisotropic minimum-dissipation (AMD) model [Rozema et al., Phys. Fluids 27, 085107 (2015), 10.1063/1.4928700], which has many desirable properties. It is more cost effective than the dynamic Smagorinsky model, it appropriately switches off in laminar and transitional flows, and it is consistent with the exact subfilter stress tensor on both isotropic and anisotropic grids. In this study, an extension of this approach to modeling the subfilter scalar flux is proposed. The performance of the AMD model is tested in the simulation of a high-Reynolds-number rough-wall boundary-layer flow with a constant and uniform surface scalar flux. The simulation results obtained from the AMD model show good agreement with well-established empirical correlations and theoretical predictions of the resolved flow statistics. In particular, the AMD model is capable of accurately predicting the expected surface-layer similarity profiles and power spectra for both velocity and scalar concentration.

The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

PubMed

Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

2015-12-01

To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. Published by Elsevier Inc.

Localized effects of coal mine drainage on fish assemblages in a Cumberland Plateau stream in Tennessee

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schorr, M.S.; Backer, J.C.

2006-03-15

The upper watershed of North Chickamauga Creek (NCC), a fourth-order tributary to the Tennessee River, Tennessee, has been impacted by decades of acid mine drainage (AMD) from abandoned coal mines. We assessed fish assemblages, pH, conductivity, and sediment coverage at 12 study reaches (six AMD sites and six reference sites) in the Cumberland Plateau region of the NCC system, May-September 1998. Stream pH increased (3.6 to 6.0) and conductivity decreased (296 to 49 {mu}S/cm) downstream of the AMD-impacted area; however, no discernable gradient was observed in sediment cover. Elevated conductivity at AMD-impacted sites reflected increased concentrations of dissolved metals andmore » other inorganic ions. Reference sites exhibited higher pH (6.0-6.4) and lower conductivity (13-28 {mu}S/cm). Acidified reaches were characterized by low fish species richness and abundance; no fish were observed at sites where the mean pH was {lt} 5. Centrarchids (mostly bluegill (Lepomis macrochirus) and green sunfish (L. cyanellus)) comprised {gt} 90 % of the catch at AMD sites, whereas cypriniids (creek chub (Semotilus atromaculatus) and blacknose dace (Rhinichthys atratulus)) accounted for {gt} 90 % of the catch at reference sites. Findings from this study document the negative effects of acid drainage from coal mines on fish assemblages in a Cumberland Plateau stream.« less

Manned space flight nuclear system safety. Volume 3: Reactor system preliminary nuclear safety analysis. Part 2: Accident Model Document (AMD)

NASA Technical Reports Server (NTRS)

1972-01-01

The Accident Model Document is one of three documents of the Preliminary Safety Analysis Report (PSAR) - Reactor System as applied to a Space Base Program. Potential terrestrial nuclear hazards involving the zirconium hydride reactor-Brayton power module are identified for all phases of the Space Base program. The accidents/events that give rise to the hazards are defined and abort sequence trees are developed to determine the sequence of events leading to the hazard and the associated probabilities of occurence. Source terms are calculated to determine the magnitude of the hazards. The above data is used in the mission accident analysis to determine the most probable and significant accidents/events in each mission phase. The only significant hazards during the prelaunch and launch ascent phases of the mission are those which arise form criticality accidents. Fission product inventories during this time period were found to be very low due to very limited low power acceptance testing.

PGC-1α repression and high fat diet induce age-related macular degeneration-like phenotypes in mice.

PubMed

Zhang, Meng; Chu, Yi; Mowery, Joseph; Konkel, Brandon; Galli, Susana; Theos, Alexander C; Golestaneh, Nady

2018-06-20

Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE (AMD RPE-iPSC-RPE). To further investigate the effect of PGC-1α repression we have established a mouse model by feeding PGC-1α + /- mice with high fat diet (HFD) and investigated the RPE and retinal health. Here we show that when mice expressing lower levels of Pgc-1α are exposed to HFD, they present AMD-like abnormalities in RPE and retinal morphology and function. These abnormalities include basal laminar deposits, thickening of Bruch's membrane (BM) with drusen marker-containing deposits, RPE and photoreceptor degeneration, decreased mitochondrial activity, increased ROS levels, decreased autophagy dynamics/ flux, and increased inflammatory response in the RPE/retina. Our study show that the PGC-1α is important in outer retina biology and that PGC-1α + /- mouse fed with HFD is a promising model to study AMD and opens doors for novel treatment strategies in AMD. © 2018. Published by The Company of Biologists Ltd.

Inferring diagnosis and trajectory of wet age-related macular degeneration from OCT imagery of retina

NASA Astrophysics Data System (ADS)

Irvine, John M.; Ghadar, Nastaran; Duncan, Steve; Floyd, David; O'Dowd, David; Lin, Kristie; Chang, Tom

2017-03-01

Quantitative biomarkers for assessing the presence, severity, and progression of age-related macular degeneration (AMD) would benefit research, diagnosis, and treatment. This paper explores development of quantitative biomarkers derived from OCT imagery of the retina. OCT images for approximately 75 patients with Wet AMD, Dry AMD, and no AMD (healthy eyes) were analyzed to identify image features indicative of the patients' conditions. OCT image features provide a statistical characterization of the retina. Healthy eyes exhibit a layered structure, whereas chaotic patterns indicate the deterioration associated with AMD. Our approach uses wavelet and Frangi filtering, combined with statistical features that do not rely on image segmentation, to assess patient conditions. Classification analysis indicates clear separability of Wet AMD from other conditions, including Dry AMD and healthy retinas. The probability of correct classification of was 95.7%, as determined from cross validation. Similar classification analysis predicts the response of Wet AMD patients to treatment, as measured by the Best Corrected Visual Acuity (BCVA). A statistical model predicts BCVA from the imagery features with R2 = 0.846. Initial analysis of OCT imagery indicates that imagery-derived features can provide useful biomarkers for characterization and quantification of AMD: Accurate assessment of Wet AMD compared to other conditions; image-based prediction of outcome for Wet AMD treatment; and features derived from the OCT imagery accurately predict BCVA; unlike many methods in the literature, our techniques do not rely on segmentation of the OCT image. Next steps include larger scale testing and validation.

Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach.

PubMed

Fraccaro, Paolo; Nicolo, Massimo; Bonetto, Monica; Giacomini, Mauro; Weller, Peter; Traverso, Carlo Enrico; Prosperi, Mattia; OSullivan, Dympna

2015-01-27

To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) "black-box" approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients' attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians' decision pathways to diagnose AMD. Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.

Thermal Stimulation of the Retina Reduces Bruch's Membrane Thickness in Age Related Macular Degeneration Mouse Models.

PubMed

Tode, Jan; Richert, Elisabeth; Koinzer, Stefan; Klettner, Alexa; von der Burchard, Claus; Brinkmann, Ralf; Lucius, Ralph; Roider, Johann

2018-05-01

To investigate the effect of thermal stimulation of the retina (TS-R) on Bruch's membrane (BrM) thickness in age-related macular degeneration (AMD) mouse models as a novel concept for the prophylaxis and treatment of dry AMD. Two knockout AMD mouse models, B6.129P2-Apoe tm1Unc /J (ApoE-/-) and B6.129X1-Nfe2I2 tm1Ywk /J (NRF2-/-), were chosen. One randomized eye of each mouse in four different groups (two of different age, two of different genotype) of five mice was treated by TS-R (532 nm, 10-ms duration, 50-μm spot size), the fellow eye served as control. Laser power was titrated to barely visible laser burns, then reduced by 70% to guarantee for thermal elevation without damage to the neuroretina, then applied uniformly to the murine retina. Fundus, optical coherence tomography (OCT), and fluorescein angiography (FLA) images were obtained at the day of treatment and 1 month after treatment. Eyes were enucleated thereafter to analyze BrM thickness by transmission electron microscopy (TEM) in a standardized blinded manner. Fundus images revealed that all ApoE-/- and NRF2-/- mice had AMD associated retinal alterations. BrM thickness was increased in untreated controls of both mouse models. Subvisible TS-R laser spots were not detectable by fundus imaging, OCT, or FLA 2 hours or 1 month after laser treatment. TEM revealed a significant reduction of BrM thickness in laser-treated eyes of all four groups compared to their fellow control eyes. TS-R reduces BrM thickness in AMD mouse models ApoE-/- and NRF2-/- without damage to the neuroretina. It may become a prophylactic or even therapeutic treatment option for dry AMD. TS-R may become a prophylactic or even therapeutic treatment option for dry AMD.

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

PubMed Central

Whitmore, S.Scott; Sohn, Elliott H.; Chirco, Kathleen R.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.

2015-01-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. PMID:25486088

Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.

PubMed

Whitmore, S Scott; Sohn, Elliott H; Chirco, Kathleen R; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

2015-03-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

PubMed Central

Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin

2018-01-01

Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Methods Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. Results In any 5-year duration, 19–28% of unilateral any AMD cases became bilateral and 27–68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. Conclusion One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement. PMID:28108569

Regulatory Forum Opinion Piece*: Use and Utility of Animal Models of Disease for Nonclinical Safety Assessment: A Pharmaceutical Industry Survey.

PubMed

Morgan, Sherry J; Couch, Jessica; Guzzie-Peck, Peggy; Keller, Douglas A; Kemper, Ray; Otieno, Monicah A; Schulingkamp, Robert J; Jones, Thomas W

2017-04-01

An Innovation and Quality (IQ) Consortium focus group conducted a cross-company survey to evaluate current practices and perceptions around the use of animal models of disease (AMDs) in nonclinical safety assessment of molecules in clinical development. The IQ Consortium group is an organization of pharmaceutical and biotechnology companies with the mission of advancing science and technology. The survey queried the utilization of AMDs during drug discovery in which drug candidates are evaluated in efficacy models and limited short-duration non-Good Laboratory Practices (GLP) toxicology testing and during drug development in which drug candidates are evaluated in GLP toxicology studies. The survey determined that the majority of companies used AMDs during drug discovery primarily as a means for proactively assessing potential nonclinical safety issues prior to the conduct of toxicology studies, followed closely by the use of AMDs to better understand toxicities associated with exaggerated pharmacology in traditional toxicology models or to derisk issues when the target is only expressed in the disease state. In contrast, the survey results indicated that the use of AMDs in development is infrequent, being used primarily to investigate nonclinical safety issues associated with targets expressed only in disease states and/or in response to requests from global regulatory authorities.

Healthy Lifestyles Related to Subsequent Prevalence of Age-Related Macular Degeneration

PubMed Central

Mares, JA; Voland, R.; Sondel, SA; Millen, A.E.; LaRowe, T; Moeller, SM; Klein, M.L.; Blodi, B.A; Chappell, R.; Tinker, L.; Ritenbaugh, C; Gehrs, K; Sarto, G; Johnson, E.J; Snodderly, M; Wallace, RB

2010-01-01

Purpose The relationships between lifestyle behaviors of diet, smoking and physical activity and the subsequent prevalence of age-related macular degeneration (AMD) were investigated. Methods The population included 1,313 participants (55 to 74 years) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study (WHIOS). Scores on a modified 2005 Healthy Eating Index (mHEI) were assigned using responses to a food frequency questionnaire administered at WHIOS baseline (1994-1998). Physical activity and lifetime smoking history were queried. An average of six years later, stereoscopic fundus photographs were taken to assess presence and severity of AMD; present in 202 women, 94% of whom had early AMD, the primary outcome. Results In multivariate models, women whose diets scored in the highest compared with the lowest quintile on the mHEI had a 46% lower odds for early AMD. Women in the highest vs. lowest quintile for physical activity (MET- Hrs/Wk) had 54% lower odds for early AMD. Although smoking, alone was not independently associated with AMD, having a combination of three healthy lifestyles (healthy diet, physical activity and not smoking) was associated with a 71% lower odds for AMD compared with having high risk scores (P=0.0004). Conclusions Modifying lifestyles might reduce risk for early AMD as much as 3-fold, lowering the risk for advanced AMD in a person's lifetime and the social and economic costs of AMD to society. PMID:21149749

Final safety analysis report for the Galileo Mission: Volume 2: Book 1, Accident model document

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The Accident Model Document (AMD) is the second volume of the three volume Final Safety Analysis Report (FSAR) for the Galileo outer planetary space science mission. This mission employs Radioisotope Thermoelectric Generators (RTGs) as the prime electrical power sources for the spacecraft. Galileo will be launched into Earth orbit using the Space Shuttle and will use the Inertial Upper Stage (IUS) booster to place the spacecraft into an Earth escape trajectory. The RTG's employ silicon-germanium thermoelectric couples to produce electricity from the heat energy that results from the decay of the radioisotope fuel, Plutonium-238, used in the RTG heat source.more » The heat source configuration used in the RTG's is termed General Purpose Heat Source (GPHS), and the RTG's are designated GPHS-RTGs. The use of radioactive material in these missions necessitates evaluations of the radiological risks that may be encountered by launch complex personnel as well as by the Earth's general population resulting from postulated malfunctions or failures occurring in the mission operations. The FSAR presents the results of a rigorous safety assessment, including substantial analyses and testing, of the launch and deployment of the RTGs for the Galileo mission. This AMD is a summary of the potential accident and failure sequences which might result in fuel release, the analysis and testing methods employed, and the predicted source terms. Each source term consists of a quantity of fuel released, the location of release and the physical characteristics of the fuel released. Each source term has an associated probability of occurrence. 27 figs., 11 tabs.« less

Utilizing the Antarctic Master Directory to find orphan datasets

NASA Astrophysics Data System (ADS)

Bonczkowski, J.; Carbotte, S. M.; Arko, R. A.; Grebas, S. K.

2011-12-01

While most Antarctic data are housed at an established disciplinary-specific data repository, there are data types for which no suitable repository exists. In some cases, these "orphan" data, without an appropriate national archive, are served from local servers by the principal investigators who produced the data. There are many pitfalls with data served privately, including the frequent lack of adequate documentation to ensure the data can be understood by others for re-use and the impermanence of personal web sites. For example, if an investigator leaves an institution and the data moves, the link published is no longer accessible. To ensure continued availability of data, submission to long-term national data repositories is needed. As stated in the National Science Foundation Office of Polar Programs (NSF/OPP) Guidelines and Award Conditions for Scientific Data, investigators are obligated to submit their data for curation and long-term preservation; this includes the registration of a dataset description into the Antarctic Master Directory (AMD), http://gcmd.nasa.gov/Data/portals/amd/. The AMD is a Web-based, searchable directory of thousands of dataset descriptions, known as DIF records, submitted by scientists from over 20 countries. It serves as a node of the International Directory Network/Global Change Master Directory (IDN/GCMD). The US Antarctic Program Data Coordination Center (USAP-DCC), http://www.usap-data.org/, funded through NSF/OPP, was established in 2007 to help streamline the process of data submission and DIF record creation. When data does not quite fit within any existing disciplinary repository, it can be registered within the USAP-DCC as the fallback data repository. Within the scope of the USAP-DCC we undertook the challenge of discovering and "rescuing" orphan datasets currently registered within the AMD. In order to find which DIF records led to data served privately, all records relating to US data within the AMD were parsed. After identifying the records containing a URL leading to a national data center or other disciplinary data repository, the remaining records were individually inspected for data type, format, and quality of metadata and then assessed to determine how best to preserve. Of the records reviewed, those for which appropriate repositories could be identified were submitted. An additional 35 were deemed acceptable in quality of metadata to register in the USAP-DCC. The content of these datasets were varied in nature, ranging from penguin counts to paleo-geologic maps to results of meteorological models all of which are discoverable through our search interface, http://www.usap-data.org/search.php. The remaining 40 records linked to either no data or had inadequate documentation for preservation highlighting the danger of serving datasets on local servers where minimal metadata standards can not be enforced and long-term access can not be ensured.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Fisher, Diana E; Klein, Barbara E K; Wong, Tien Y; Rotter, Jerome I; Li, Xiaohui; Shrager, Sandi; Burke, Gregory L; Klein, Ronald; Cotch, Mary Frances

2016-06-01

To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. Prospective cohort study. A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. Incident early and late AMD. The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study. Published by Elsevier Inc.

Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

NASA Astrophysics Data System (ADS)

Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

2003-03-01

Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

Evidence for the Stepwise Stress Model: Gambusia holbrooki and Daphnia magna under acid mine drainage and acidified reference water stress.

PubMed

Gerhardt, Almut; Janssens de Bisthoven, Luc; Soares, Amadeu M V

2005-06-01

The Stepwise Stress Model (SSM) states that a cascade of regulative behavioral responses with different intrinsic sensitivities and threshold values offers increased behavioral plasticity and thus a wider range of tolerance for environmental changes or pollutant exposures. We tested the SSM with a widely introduced fish Gambusia holbrooki (Girard) (Pisces, Poeciliidae) and the standard laboratory test species Daphnia magna Straus (Crustacea, Daphniidae). The stress was simulated by short-term exposure to acid mine drainage (AMD) and to acidified reference water (ACID). Recording of behavioral responses with the multispecies freshwater biomonitor (MFB) generated continuous time-dependent dose-response data that were modeled in three-dimensional (3D) surface plots. Both the pH-dependent mortalities and the strong linear correlations between pH and aqueous metals confirmed the toxicity of the AMD and ACID gradients, respectively, for fish and Daphnia, the latter being more sensitive. AMD stress at pH < or = 5.5 amplified circadian rhythmicity in both species, while ACID stress did so only in G. holbrooki. A behavioral stepwise stress response was found in both species: D. magna decreased locomotion and ventilation (first step) (AMD, ACID), followed by increased ventilation (second step) (AMD). G. holbrooki decreased locomotion (first step) (AMD, ACID) and increased ventilation at intermediate pH levels (second step) (AMD). Both species, although from different taxonomic groups and feeding habits, followed the SSM, which might be expanded to a general concept for describing the behavioral responses of aquatic organims to pollution. Stepwise stress responses might be applied in online biomonitors to provide more sensitive and graduated alarm settings, hence optimizing the "early warning" detection of pollution waves.

Prevalence, racial variations, and risk factors of age-related macular degeneration in Singaporean Chinese, Indians, and Malays.

PubMed

Cheung, Chui Ming Gemmy; Li, Xiang; Cheng, Ching-Yu; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin

2014-08-01

To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. Population-based cross-sectional study. A total of 10 033 persons (3280 Malay, 3400 Indian, and 3353 Chinese; response rate, 75%) 40 years of age or older residing in Singapore. We performed comprehensive systemic and ocular examinations, retinal photography, and laboratory investigations for all participants. We graded early and late AMD signs from retinal photographs using the modified Wisconsin AMD grading scale. We calculated the age-standardized prevalence of AMD using the 2010 Singapore adult population and analyzed risk factors for AMD using logistic regression models. Early and late AMD. Of the 9799 participants with gradable photographs, 588 had early AMD and 60 had late AMD. The age-standardized prevalence was 5.1% (95% confidence interval [CI], 4.6-5.5) for early AMD and 0.5% (95% CI, 0.4-0.6) for late AMD. The prevalence of early AMD was similar between Chinese (5.7%) and Indian (4.5%; P = 0.27) persons and lower in Malays (3.5%; P = 0.002 compared with Chinese; P = 0.09 compared with Indians); in contrast, the prevalence for late AMD was similar across ethnic groups (Chinese, 0.6%; Indian, 0.3%; and Malay, 0.3%; P = 0.20). Risk factors for early AMD were older age (odds ratio [OR], 1.40 per 5-year increase in age; 95% CI, 1.33-1.47), male gender (OR, 1.81; 95% CI, 1.43-2.29), hypertension (OR, 1.28; 95% CI, 1.02-1.61), and hyperopic refraction (OR, 1.17 per 1-diopter increase in spherical equivalent; 95% CI, 1.11-1.24). Risk factors for late AMD include older age (OR, 1.87 per 5-year increase in age; 95% CI, 1.54-2.19), smoking more than 5 packs per week (OR, 3.63; 95% CI, 1.34-9.80), and presence of chronic kidney disease (OR, 2.17; 95% CI, 1.22-3.88). Early AMD is more common in Chinese and Indians than in Malays, but there were no racial variations in the prevalence of late AMD. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Identification of vinculin as a potential plasma marker for age-related macular degeneration.

PubMed

Kim, Hye-Jung; Woo, Se Joon; Suh, Eui Jin; Ahn, Jeeyun; Park, Ji Hyun; Hong, Hye Kyoung; Lee, Ji Eun; Ahn, Seong Joon; Hwang, Duck Jin; Kim, Ki Woong; Park, Kyu Hyung; Lee, Cheolju

2014-10-08

To identify plasma protein biomarkers for age-related macular degeneration (AMD) using a large-scale quantitative proteomic discovery procedure. Plasma proteomes from 20 exudative AMD patients and 20 healthy control patients were comparatively profiled by four-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins existing at statistically different levels were validated by enzyme-linked immunosorbent assay (ELISA) and Western blotting in 233 case-controlled samples. Newly discovered plasma biomarkers were further confirmed using in vivo and in vitro experiments. Out of 320 proteins identified, vinculin, protein S100A9, triosephosphate isomerase, protein S100A8, protein Z-dependent protease inhibitor, C-X-C motif chemokine 7, and tenascin X showed significantly differential expression in AMD patient plasma compared to control plasma. Among these, the area under the curve (AUC) for vinculin was 0.871 for discriminating between exudative AMD and controls (n = 201) and 0.879 for discriminating between AMD and controls (n = 233). A proteogenomic combination model using vinculin and two known risk genotypes in ARMS2 and CFH genes additionally provided excellent discrimination of AMD from controls (AUC = 0.916). The plasma level of vinculin was not associated with any confounding clinical variables, such as age, smoking, and other comorbidities. Additionally, vinculin was strongly expressed in retinal pigment epithelial cells of human eyes, and its expression was elevated when exposed to oxidative stress in vitro. Vinculin was identified as a potential plasma biomarker for AMD. The early detection of AMD using novel plasma biomarkers with genetic modeling may enable timely treatment and vision preservation in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

A bio-inspired device for drag reduction on a three-dimensional model vehicle.

PubMed

Kim, Dongri; Lee, Hoon; Yi, Wook; Choi, Haecheon

2016-03-10

In this paper, we introduce a bio-mimetic device for the reduction of the drag force on a three-dimensional model vehicle, the Ahmed body (Ahmed et al 1984 SAE Technical Paper 840300). The device, called automatic moving deflector (AMD), is designed inspired by the movement of secondary feathers on bird's wing suction surface: i.e., secondary feathers pop up when massive separation occurs on bird's wing suction surface at high angles of attack, which increases the lift force at landing. The AMD is applied to the rear slanted surface of the Ahmed body to control the flow separation there. The angle of the slanted surface considered is 25° at which the drag coefficient on the Ahmed body is highest. The wind tunnel experiment is conducted at Re H  = 1.0 × 10(5)-3.8 × 10(5), based on the height of the Ahmed body (H) and the free-stream velocity (U ∞). Several AMDs of different sizes and materials are tested by measuring the drag force on the Ahmed body, and showed drag reductions up to 19%. The velocity and surface-pressure measurements show that AMD starts to pop up when the pressure in the thin gap between the slanted surface and AMD is much larger than that on the upper surface of AMD. We also derive an empirical formula that predicts the critical free-stream velocity at which AMD starts to operate. Finally, it is shown that the drag reduction by AMD is mainly attributed to a pressure recovery on the slanted surface by delaying the flow separation and suppressing the strength of the longitudinal vortices emanating from the lateral edges of the slanted surface.

Associations of candidate genes to age-related macular degeneration among racial/ethnic groups in the multi-ethnic study of atherosclerosis.

PubMed

Klein, Ronald; Li, Xiaohui; Kuo, Jane Z; Klein, Barbara E K; Cotch, Mary Frances; Wong, Tien Y; Taylor, Kent D; Rotter, Jerome I

2013-11-01

To describe the relationships of selected candidate genes to the prevalence of early age-related macular degeneration (AMD) in a cohort of whites, blacks, Hispanics, and Chinese Americans. Cross-sectional study. setting: Multicenter study. study population: A total of 2456 persons aged 45-84 years with genotype information and fundus photographs. procedures: Twelve of 2862 single nucleotide polymorphisms (SNPs) from 11 of 233 candidate genes for cardiovascular disease were selected for analysis based on screening with marginal unadjusted P value <.001 within 1 or more racial/ethnic groups. Logistic regression models tested for association in case-control samples. main outcome measure: Prevalence of early AMD. Early AMD was present in 4.0% of the cohort and varied from 2.4% in blacks to 6.0% in whites. The odds ratio increased from 2.3 for 1 to 10.0 for 4 risk alleles in a joint effect analysis of Age-Related Maculopathy Susceptibility 2 rs10490924 and Complement Factor H Y402H (P for trend = 4.2×10(-7)). Frequencies of each SNP varied among the racial/ethnic groups. Adjusting for age and other factors, few statistically significant associations of the 12 SNPs with AMD were consistent across all groups. In a multivariate model, most candidate genes did not attenuate the comparatively higher odds of AMD in whites. The higher frequency of risk alleles for several SNPs in Chinese Americans may partially explain their AMD frequency's approaching that of whites. The relationships of 11 candidate genes to early AMD varied among 4 racial/ethnic groups, and partially explained the observed variations in early AMD prevalence among them. Copyright © 2013 Elsevier Inc. All rights reserved.

Retinal vascular caliber, iris color, and age-related macular degeneration in the Irish Nun Eye Study.

PubMed

McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C; Maxwell, Alexander P; McKay, Gareth J

2014-12-18

To evaluate the relationship between retinal vascular caliber (RVC), iris color, and age-related macular degeneration (AMD) in elderly Irish nuns. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin Age-related Maculopathy Grading System. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction, and fellow RVC. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range, 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P < 0.05), but this was no longer significant after adjustment. Age-related macular degeneration status was categorized as no AMD, any AMD, and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis, but this was no longer significant after adjustment. A nonsignificant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Retinal vascular caliber was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but nonsignificant AMD risk was observed in those with brown compared to blue iris color. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

PubMed

Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

2016-01-01

To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

Cost-Effectiveness Models in Age-Related Macular Degeneration: Issues and Challenges.

PubMed

Schmier, Jordana K; Hulme-Lowe, Carolyn K

2016-03-01

Age-related macular degeneration (AMD) is a common ophthalmic condition that can have few symptoms in its early stage but can progress to major visual impairment. While there are no treatments for early-stage AMD, there are multiple modalities of treatment for advanced disease. Given the increasing prevalence of the disease, there are dozens of analyses of cost effectiveness of AMD treatments, but methods and approaches vary broadly. The goal of this review was to identify, characterize, and critique published models in AMD and provide guidance for their interpretation. After a literature review was performed to identify studies, and exclusion criteria applied to limit the review to studies comparing treatments for AMD, we compared methods across the 36 studies meeting the review criteria. To some extent, variation was related to targeting different audiences or acknowledging the most appropriate population for a given treatment. However, the review identified potential areas of uncertainty and difficulty in interpretation, particularly regarding duration of observation periods and the importance of visual acuity as an endpoint or a proxy for patient-reported utilities. We urge thoughtful consideration of these study characteristics when comparing results.

KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration.

PubMed

Muraoka, Yuki; Iida, Yuto; Ikeda, Hanako O; Iwai, Sachiko; Hata, Masayuki; Iwata, Takeshi; Nakayama, Mao; Shimozawa, Nobuhiro; Katakai, Yuko; Kakizuka, Akira; Yoshimura, Nagahisa; Tsujikawa, Akitaka

2018-05-01

Age-related macular degeneration (AMD) is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD. Systemic administration of KUS121 prevented or reduced drusen-like lesions and endoplasmic reticulum stress, and then substantially mitigated chorioretinal pathologies with significant preservation of visual function. Additionally, we confirmed that long-term oral administration of KUS121 caused no systemic complications in drusen-affected monkeys. ATP regulation by KUSs may represent a novel strategy in the treatment of drusen and prevention of disease progression in AMD.

Impact of Legacy Surface Mining on Water Quality in the Lake Harris Watershed, Tuscaloosa County, Alabama.

NASA Astrophysics Data System (ADS)

Donahoe, R. J.; Hawkins, P. D.

2017-12-01

The Lake Harris watershed was the site of legacy surface mining of coal conducted from approximately 1969 to 1976. The mine site was abandoned and finally reclaimed in 1986. Water quality in the stream draining the mined area is still severely impacted by acid mine drainage (AMD), despite the reclamation effort. Lake Harris is used as a source of industrial water, but shows no negative water quality effects from the legacy mining activities despite receiving drainage from the AMD-impacted stream. Water samples were collected monthly between October 2016 and September 2017 from a first-order stream impacted by acid mine drainage (AMD), a nearby first-order control stream, and Lake Harris. Stream water chemistry was observed to vary both spatially and seasonally, as monitored at five sample stations in each stream over the study period. Comparison of the two streams shows the expected elevated concentrations of AMD-indicator solutes (sulfate and iron), as well as significant increases in conductivity and acidity for the stream draining the reclaimed mine site. In addition, dramatic (1-2 orders of magnitude) increases in major element (Al, Ca, Mg, K), minor element (Mn, Sr) and trace element (Co, Ni) concentrations are also observed for the AMD-impacted stream compared to the control stream. The AMD-impacted stream also shows elevated (2-4 times) levels of other stream water solutes (Cl, Na, Si, Zn), compared to the control stream. As the result of continuing AMD input, the stream draining the reclaimed mine site is essentially sterile, in contrast to the lake and control stream, which support robust aquatic ecosystems. A quantitative model, constrained by isotopic data (δD and δ18O), will be presented that seeks to explain the observed temporal differences in water quality for the AMD-impacted stream as a function of variable meteoric water, groundwater, and AMD inputs. Similar models may be developed for other AMD-impacted streams to better understand and predict temporal variations in water quality parameters and their effect on aquatic ecosystems.

The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

PubMed Central

Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

2015-01-01

Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the progression to late AMD in the AREDS2 participants, and these findings are consistent with the findings in the majority of previous studies. Statins have been demonstrated to reduce the risks of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. PMID:26435335

C-Reactive Protein and the Incidence of Macular Degeneration – Pooled Analysis of 5 Cohorts

PubMed Central

Mitta, Vinod P.; Christen, William G.; Glynn, Robert J.; Semba, Richard D.; Ridker, Paul M.; Rimm, Eric B.; Hankinson, Susan E.; Schaumberg, Debra A.

2013-01-01

Objectives To investigate the relationship between high-sensitivity C-reactive protein (hsCRP) and future risk of age-related macular degeneration (AMD) in US men and women. Methods We measured hsCRP in baseline blood samples from participants in five ongoing cohort studies. Patients were initially free of AMD. We prospectively identified 647 incident cases of AMD and selected age- and sex-matched controls for each AMD case (2 controls for each case with dry AMD, or 3 controls for each case of neovascular AMD). We used conditional logistic regression models to examine the relationship between hsCRP and AMD, and pooled findings using meta-analytic techniques. Results After adjusting for cigarette smoking status, participants with high (> 3 mg/L) compared with low (< 1 mg/L) hsCRP levels, had cohort-specific odds ratios (OR) for incident AMD ranging from 0.94 (95% CI 0.58-1.51) in the Physicians’ Health Study to 2.59 (95% CI 0.58-11.67) in the Women’s Antioxidant and Folic Acid Cardiovascular Study. After testing for heterogeneity between studies (Q=5.61, p=0.23), we pooled findings across cohorts, and observed a significantly increased risk of incident AMD for high versus low hsCRP levels (OR=1.49, 95% CI 1.06-2.08). Risk of neovascular AMD was also increased among those with high hsCRP levels (OR=1.84, 95% CI 1.14-2.98). Conclusion Overall these pooled findings from 5 prospective cohorts add further evidence that elevated levels of hsCRP predict greater future risk of AMD. This information might shed light on underlying mechanisms, and could be of clinical utility in the identification of persons at high risk of AMD who may benefit from increased adherence to lifestyle recommendations, eye examination schedules, and therapeutic protocols. PMID:23392454

Fundus autofluorescence and fate of glycoxidized particles injected into subretinal space in rabbit age-related macular degeneration model.

PubMed

Hirata, Megumi; Yasukawa, Tsutomu; Wiedemann, Peter; Kimura, Erika; Kunou, Noriyuki; Eichler, Wolfram; Takase, Ayae; Sato, Rina; Ogura, Yuichiro

2009-07-01

Abnormal fundus autofluorescence (FAF) is associated with the incidence or progression of dry and wet age-related macular degeneration (AMD). We previously developed a rabbit AMD model with drusen and type-1 choroidal neovascularization (CNV) that mimics the accumulation of lipofuscin using artificial glycoxidized particles. The objective of the current study was to investigate in vitro effects of glycoxidized particles on retinal pigment epithelial (RPE) cells, and the FAF and fate of injected particles in this model. Glycoxidized particles were prepared by a 4-day incubation of water-in-oil emulsions of serum albumin and glycolaldehyde to allow glycoxidation and consequent cross-linking. After particles were added in the culture medium of confluent human RPE cells, cell viability, adhesion activity, and proliferation activity were assessed by cell counting. In anesthetized rabbits, 250 microg of glycoxidized particles were injected into the subretinal space to induce experimental AMD. FAF measurement and angiography with sodium fluorescein and indocyanine green were performed periodically using the Heidelberg Retina Angiograph 2 (HRA2). The eyes enucleated, and the lung and the spleen, excised at week 4 or 12, were histologically evaluated by light and fluorescence microscopy. Glycoxidized particles phagocytosed did not impair the cell viability, adhesion, and proliferation of RPE cells, as compared with RPE cells in controls. HRA2 showed different patterns of abnormal FAF in the area with the implanted glycoxidized particles, similar to pathological FAF patterns in aging human eyes with or without AMD. Histologic examination showed accumulated glycoxidized particles and large lipofuscin granules with green autofluorescence in and under the RPE and at the margins of or beneath drusen, possibly associated with abnormal FAF. In addition, some particles were detected in the lung and the spleen. Glycoxidized particles phagocytosed might stay in RPE cells without any acute biological reaction. Our rabbit model of AMD simulated abnormal FAF patterns observed in aging human eyes with or without AMD. Glycoxidized particles phagocytosed by RPE cells could be deposited on Bruch's membrane in rabbits, possibly excreted in part into choroidal circulation. This model may be useful for understanding various patterns of abnormal FAF histologically, and for elucidating the pathogenesis of AMD.

MINE WASTE TECHNOLOGY PROGRAM - SULFATE REDUCING BACTERIA REACTIVE WALL DEMO

EPA Science Inventory

Efforts reported in this document focused on the demonstration of a passive technology that could be used for remediation of
thousands of abandoned mines existing in the Western United States that emanate acid mine drainage (AMD). This passive remedial technology takes ad...

Automated Age-related Macular Degeneration screening system using fundus images.

PubMed

Kunumpol, P; Umpaipant, W; Kanchanaranya, N; Charoenpong, T; Vongkittirux, S; Kupakanjana, T; Tantibundhit, C

2017-07-01

This work proposed an automated screening system for Age-related Macular Degeneration (AMD), and distinguishing between wet or dry types of AMD using fundus images to assist ophthalmologists in eye disease screening and management. The algorithm employs contrast-limited adaptive histogram equalization (CLAHE) in image enhancement. Subsequently, discrete wavelet transform (DWT) and locality sensitivity discrimination analysis (LSDA) were used to extract features for a neural network model to classify the results. The results showed that the proposed algorithm was able to distinguish between normal eyes, dry AMD, or wet AMD with 98.63% sensitivity, 99.15% specificity, and 98.94% accuracy, suggesting promising potential as a medical support system for faster eye disease screening at lower costs.

Sustainable Management of Flowback Water during Hydraulic Fracturing of Marcellus Shale for Natural Gas Production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vidic, Radisav

2015-01-24

This study evaluated the feasibility of using abandoned mine drainage (AMD) as make- up water for the reuse of produced water for hydraulic fracturing. There is an abundance of AMD sources near permitted gas wells as documented in this study that can not only serve as makeup water and reduce the demand on high quality water resources but can also as a source of chemicals to treat produced water prior to reuse. The assessment of AMD availability for this purpose based on proximity and relevant regulations was accompanied by bench- and pilot-scale studies to determine optimal treatment to achieve desiredmore » water quality for use in hydraulic fracturing. Sulfate ions that are often present in AMD at elevated levels will react with Ba²⁺ and Sr²⁺ in produced water to form insoluble sulfate compounds. Both membrane microfiltration and gravity separation were evaluated for the removal of solids formed as a result of mixing these two impaired waters. Laboratory studies revealed that neither AMD nor barite formed in solution had significant impact on membrane filtration but that some produced waters contained submicron particles that can cause severe fouling of microfiltration membrane. Coagulation/flocculation was found to be an effective process for the removal of suspended solids and both bench- and pilot-scale studies revealed that optimal process conditions can consistently achieve the turbidity of the finished water below 5 NTU. Adjusting the blending ratio of AMD and produced water can achieve the desired effluent sulfate concentration that can be accurately predicted by chemical thermodynamics. Co-treatment of produced water and AMD will result in elevated levels of naturally occurring radioactive materials (NORM) in the solid waste generated in this process due to radium co-precipitation with barium sulfate. Laboratory studies revealed that the mobility of barite that may form in the subsurface due to the presence of sulfate in the fracturing fluid can be controlled by the addition of appropriate antiscalants.« less

Fate of Acrylamide in Soil and Groundwater Systems: Microbial Degradation

NASA Astrophysics Data System (ADS)

Labahn, S.; Moser, D.; Arrowood, T.; Young, M.; Robleto, E.

2007-12-01

Acrylamide monomer (AMD), a suspected human neurotoxin and carcinogen, is present as a contaminant (up to 0.05%) in commercial preparations of polyacrylamide (PAM). PAM is currently being evaluated for wide-spread use as a temporary water-delivery canal sealant across the western United States. To better constrain potential risks associated with PAM applications, we examined the capacity of natural canal microorganisms to degrade AMD in laboratory and field experiments. Dilution cultivation and enrichment approaches were employed to determine the abundance of culturable microorganisms in several canal habitats which can utilize AMD as a sole nitrogen source (typically 104-106/mL) and a collection of isolates was developed. AMD-degrading microorganisms in our collection fell within a limited diversity of genera including Arthrobacter, Xanthomonas, and Pseudomonas; with the latter demonstrating highest capacity for degrading AMD under laboratory conditions. One strain of Pseudomonas fluorescens, isolated from Klamath Irrigation District (Klamath Falls, OR) canal sediment, was chosen for further study in part because this species is well-studied and ubiquitous. The potential for microbial AMD degradation was tested under laboratory conditions using this strain in repacked short (15 cm) column tests with two relevant soil types (sand and loam). Subsequently, the capacity of mixed natural microbial populations to degrade AMD was examined using soil cores collected from the Highline Canal (Rocky Ford, CO), and canal water/sediment slurries with spiked (5 ppm AMD) in situ bottle tests. Degradation of the monomer in the repacked column experiments was evaluated using a step input of 5 ppm AMD and the canal columns were tested with a range of AMD concentrations (1-5 ppm) followed by quantification with an HPLC. The repacked soil columns inoculated with P. fluorescens demonstrated 80-100% AMD degradation within 12 hours. Natural microbial communities in fresh canal sediment columns produced varying levels of AMD degradation, ranging from 40-50% after 36 hours. The in situ bottle test resulted in 50% degradation after 72 hours. Experimental AMD degradation rates and transport parameters, such as sorption and retardation, were combined to model AMD transport in canal and ground water systems (Arrowood et al. 2007). Initial calculations demonstrate the importance of the microbial role in removal of the monomer and infer possible implications informing the development of safe and effective PAM application protocols.

Association of Anticholinergic Drug Use With Risk for Late Age-Related Macular Degeneration.

PubMed

Aldebert, Gauthier; Faillie, Jean-Luc; Hillaire-Buys, Dominique; Mura, Thibault; Carrière, Isabelle; Delcourt, Cécile; Creuzot-Garcher, Catherine; Villain, Max; Daien, Vincent

2018-05-24

Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017. Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated. Association between exposure to ACDs and late AMD. Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P = .007), high Anticholinergic Burden Score (≥3) (aOR, 6.42; 95% CI, 1.38-29.92; P = .02), and longest cumulative exposure to ACD (≥15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P = .03). Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose-effect association was suggested by a greater association with prolonged use and high Anticholinergic Burden Score. Further studies, in particular those with longitudinal design, are needed to confirm this association.

Environmental and Agricultural Sciences. Georgia Core Standards for Occupational Clusters.

ERIC Educational Resources Information Center

Georgia Univ., Athens. Dept. of Occupational Studies.

This document lists core standards and occupational knowledge amd skills that have been identified/validated by industry as necessary to all Georgia students in secondary-level environmental and agricultural sciences programs. First, foundation skills are grouped as follows: basic skills (reading, writing, arithmetic/mathematics, listening,…

Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women

PubMed Central

Millen, Amy E.; Voland, Rick; Sondel, Sherie A.; Parekh, Niyati; Horst, Ronald L.; Wallace, Robert B.; Hageman, Gregory S.; Chappell, Rick; Blodi, Barbara A.; Klein, Michael L.; Gehrs, Karen M.; Sarto, Gloria E.; Mares, Julie A.

2010-01-01

Objective The relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated among participants of the Carotenoids in Age-Related Eye Disease Study. Methods Stereoscopic fundus photographs, taken from 2001–2004, assessed AMD status. Baseline (1994–1998) serum samples were available for 25(OH)D assays in 1,313 women with complete ocular and risk factor data. Odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD (n=241), among 1,287 without advanced disease, were estimated with logistic regression and adjusted for age, smoking, iris pigmentation, family history of AMD, cardiovascular disease, diabetes, and hormone therapy use. Results In multivariate models, no significant relationship was observed between early AMD and 25(OH)D (OR for quintile 5 vs. 1=0.79, 95% CI=0.50–1.24; p for trend=0.47). A significant age interaction (p=0.0025) suggested selective mortality bias in women ≥75 years: serum 25(OH)D was associated with decreased odds of early AMD in women <75 years (n=968) and increased odds in women ≥75 years (n=319) (OR for quintile 5 vs. 1=0.52, 95% CI=0.29–0.91; p for trend=0.02 and 1.76, 95% CI=0.77–4.13; p for trend=0.05, respectively). Further adjustment for body mass index and recreational physical activity, predictors of 25(OH)D, attenuated the observed association in women <75 years. Additionally, among women <75 years, intake of vitamin D from foods and supplements was related to decreased odds of early AMD in multivariate models; no relationship was observed with self-reported time spent in direct sunlight. Conclusions High serum 25(OH)D concentrations may protect against early AMD in women <75 years. PMID:21482873

Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration.

PubMed

Ding, Jin-Dong; Johnson, Lincoln V; Herrmann, Rolf; Farsiu, Sina; Smith, Stephanie G; Groelle, Marybeth; Mace, Brian E; Sullivan, Patrick; Jamison, Jeffrey A; Kelly, Una; Harrabi, Ons; Bollini, Sangeetha Subbarao; Dilley, Jeanette; Kobayashi, Dione; Kuang, Bing; Li, Wenlin; Pons, Jaume; Lin, John C; Bowes Rickman, Catherine

2011-07-12

Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid β (Aβ) peptides, Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), have been implicated previously in the AMD disease process. Consistent with a pathogenic role for Aβ, we show here that a mouse model of AMD that invokes multiple factors that are known to modify AMD risk (aged human apolipoprotein E 4 targeted replacement mice on a high-fat, cholesterol-enriched diet) presents with Aβ-containing deposits basal to the retinal pigmented epithelium (RPE), histopathologic changes in the RPE, and a deficit in scotopic electroretinographic response, which is reflective of impaired visual function. Strikingly, these electroretinographic deficits are abrogated in a dose-dependent manner by systemic administration of an antibody targeting the C termini of Aβ40 and Aβ42. Concomitant reduction in the levels of Aβ and activated complement components in sub-RPE deposits and structural preservation of the RPE are associated with anti-Aβ40/42 antibody immunotherapy and visual protection. These observations are consistent with the reduction in amyloid plaques and improvement of cognitive function in mouse models of Alzheimer's disease treated with anti-Aβ antibodies. They also implicate Aβ in the pathogenesis of AMD and identify Aβ as a viable therapeutic target for its treatment.

Retinal Spectral Domain Optical Coherence Tomography in Early Atrophic Age-Related Macular Degeneration (AMD) and a New Metric for Objective Evaluation of the Efficacy of Ocular Nutrition

PubMed Central

Richer, Stuart; Cho, Jane; Stiles, William; Levin, Marc; Wrobel, James S.; Sinai, Michael; Thomas, Carla

2012-01-01

Purpose: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973). Methods: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.4/4.0 bilateral retinopathy). Foveal and extra-foveal four quadrant SDOCT RT measurements were evaluated in n = 54 clinical and ZVF AMD patients. RT by age was determined and compared to the OptoVue SD OCT normative database. RT by quadrant in a subset of n = 29 ZVF patients was correlated with contrast sensitivity and parafoveal blue cone increment thresholds. Results: Foveal RT in AMD patients and non-AMD patients was preserved with age. Extrafoveal regions, however, showed significant slope differences between AMD patients and non-AMD patients, with the superior and nasal quadrants most vulnerable to retinal thinning (sup quad: −5.5 μm/decade thinning vs. Non-AMD: −1.1 μm/decade, P < 0.02; nasal quad: −5.0 μm/decade thinning vs. Non-AMD: −1.0 μm/decade, P < 0.04). Two measures of extrafoveal visual deterioration were correlated: A significant inverse correlation between % RT and contrast sensitivity (r = −0.33, P = 0.01, 2 Tailed Paired T) and an elevated extrafoveal increment blue cone threshold (r = +0.34, P = 0.01, 2 Tailed T). Additional SD OCT RT data for the non-AMD oldest age group (ages 82–91) is needed to fully substantiate the model. Conclusion: A simple new SD OCT clinical metric called “% extra-foveal RT” correlates well with functional visual loss in early AMD patients having minimal visible retinopathy. This metric can be used to follow the effect of repleting ocular nutrients, such as zinc, antioxidants, carotenoids, n-3 essential fats , resveratrol and vitamin D. PMID:23363992

An Induced Pluripotent Stem Cell Patient Specific Model of Complement Factor H (Y402H) Polymorphism Displays Characteristic Features of Age-Related Macular Degeneration and Indicates a Beneficial Role for UV Light Exposure.

PubMed

Hallam, Dean; Collin, Joseph; Bojic, Sanja; Chichagova, Valeria; Buskin, Adriana; Xu, Yaobo; Lafage, Lucia; Otten, Elsje G; Anyfantis, George; Mellough, Carla; Przyborski, Stefan; Alharthi, Sameer; Korolchuk, Viktor; Lotery, Andrew; Saretzki, Gabriele; McKibbin, Martin; Armstrong, Lyle; Steel, David; Kavanagh, David; Lako, Majlinda

2017-11-01

Age-related macular degeneration (AMD) is the most common cause of blindness, accounting for 8.7% of all blindness globally. Vision loss is caused ultimately by apoptosis of the retinal pigment epithelium (RPE) and overlying photoreceptors. Treatments are evolving for the wet form of the disease; however, these do not exist for the dry form. Complement factor H polymorphism in exon 9 (Y402H) has shown a strong association with susceptibility to AMD resulting in complement activation, recruitment of phagocytes, RPE damage, and visual decline. We have derived and characterized induced pluripotent stem cell (iPSC) lines from two subjects without AMD and low-risk genotype and two patients with advanced AMD and high-risk genotype and generated RPE cells that show local secretion of several proteins involved in the complement pathway including factor H, factor I, and factor H-like protein 1. The iPSC RPE cells derived from high-risk patients mimic several key features of AMD including increased inflammation and cellular stress, accumulation of lipid droplets, impaired autophagy, and deposition of "drüsen"-like deposits. The low- and high-risk RPE cells respond differently to intermittent exposure to UV light, which leads to an improvement in cellular and functional phenotype only in the high-risk AMD-RPE cells. Taken together, our data indicate that the patient specific iPSC model provides a robust platform for understanding the role of complement activation in AMD, evaluating new therapies based on complement modulation and drug testing. Stem Cells 2017;35:2305-2320. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Ethnic Differences in the Association Between Age-Related Macular Degeneration and Vision-Specific Functioning

PubMed Central

Fenwick, Eva K.; Man, Ryan E. K.; Cheung, Chui Ming Gemmy; Sabanayagam, Charumathi; Cheng, Ching-Yu; Neelam, Kumari; Chua, Jacqueline; Gan, Alfred T. L.; Mitchell, Paul; Wong, Tien Y.

2017-01-01

Importance Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF). Objective To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD. Design, Setting, and Participants This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016. Exposures Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System. Main Outcomes and Measures Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF. Results Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was associated with a small reduction in VSF (2.9%; β = −0.12; 95% CI, −0.23 to −0.00; P = .046) in the Chinese group but not in the Indian and Malay groups. Moreover, Chinese participants with late AMD had a clinically significant 19.1% loss of VSF (β = −0.78; 95% CI, −1.13 to −0.43, P < .001). In the Malay group, those with late AMD had a 13.5% drop in VSF (β = −0.49; 95% CI, −1.01 to 0.04; P = .07) compared with their counterparts without AMD. Similarly, late AMD was not associated with VSF in the Indian group. Conclusions and Relevance Early and late AMD negatively affected VSF in Chinese but not in Indian and Malay participants. This finding suggests that there is an independent ethnic influence in the association of the disease with VSF in multiethnic Asian populations, thus warranting ethnicity-based strategies to delay the onset or progression of AMD. PMID:28358956

Assessing Susceptibility to Age-Related Macular Degeneration With Genetic Markers and Environmental Factors

PubMed Central

Chen, Yuhong; Zeng, Jiexi; Zhao, Chao; Wang, Kevin; Trood, Elizabeth; Buehler, Jeanette; Weed, Matthew; Kasuga, Daniel; Bernstein, Paul S.; Hughes, Guy; Fu, Victoria; Chin, Jessica; Lee, Clara; Crocker, Maureen; Bedell, Matthew; Salasar, Francesca; Yang, Zhenglin; Goldbaum, Michael; Ferreyra, Henry; Freeman, William R.; Kozak, Igor; Zhang, Kang

2014-01-01

Objectives To evaluate the independent and joint effects of genetic factors and environmental variables on advanced forms of age-related macular degeneration (AMD), including geographic atrophy and choroidal neovascularization, and to develop a predictive model with genetic and environmental factors included. Methods Demographic information, including age at onset, smoking status, and body mass index, was collected for 1844 participants. Genotypes were evaluated for 8 variants in 5 genes related to AMD. Unconditional logistic regression analyses were performed to generate a risk predictive model. Results All genetic variants showed a strong association with AMD. Multivariate odds ratios were 3.52 (95% confidence interval, 2.08-5.94) for complement factor H, CFH rs1061170 CC, 4.21 (2.30-7.70) for CFH rs2274700 CC, 0.46 (0.27-0.80) for C2 rs9332739 CC/CG, 0.44 (0.30-0.66) for CFB rs641153 TT/CT, 10.99 (6.04-19.97) for HTRA1/LOC387715 rs10490924 TT, and 2.66 (1.43-4.96) for C3 rs2230199 GG. Smoking was independently associated with advanced AMD after controlling for age, sex, body mass index, and all genetic variants. Conclusion CFH confers more risk to the bilaterality of geographic atrophy, whereas HTRA1/LOC387715 contributes more to the bilaterality of choroidal neovascularization. C3 confers more risk for geographic atrophy than choroidal neovascularization. Risk models with combined genetic and environmental factors have notable discrimination power. Clinical Relevance Early detection and risk prediction of AMD could help to improve the prognosis of AMD and to reduce the outcome of blindness. Targeting high-risk individuals for surveillance and clinical interventions may help reduce disease burden. PMID:21402993

Occurrence and role of algae and fungi in acid mine drainage environment with special reference to metals and sulfate immobilization.

PubMed

Das, Bidus Kanti; Roy, Arup; Koschorreck, Matthias; Mandal, Santi M; Wendt-Potthoff, Katrin; Bhattacharya, Jayanta

2009-03-01

Passive remediation of Acid Mine Drainage (AMD) is a popular technology under development in current research. Roles of algae and fungi, the natural residents of AMD and its attenuator are not emphasized adequately in the mine water research. Living symbiotically various species of algae and fungi effectively enrich the carbon sources that help to maintain the sulfate reducing bacterial (SRB) population in predominantly anaerobic environment. Algae produce anoxic zone for SRB action and help in biogenic alkalinity generation. While studies on algal population and actions are relatively available those on fungal population are limited. Fungi show capacity to absorb significant amount of metals in their cell wall, or by extracellular polysaccharide slime. This review tries to throw light on the roles of these two types of microorganisms and to document their activities in holistic form in the mine water environment. This work, inter alia, points out the potential and gap areas of likely future research before potential applications based on fungi and algae initiated AMD remediation can be made on sound understanding.

Evidence for an Association between Macular Degeneration and Thyroid Cancer in the Aged Population.

PubMed

Lin, Shih-Yi; Hsu, Wu-Huei; Lin, Cheng-Li; Lin, Cheng-Chieh; Lin, Jane-Ming; Chang, Yun-Lun; Hsu, Chung-Y; Kao, Chia-Hung

2018-05-03

Direct evidence of whether thyroid cancer patients have a higher risk of age-related macular degeneration (AMD) has yet to be investigated. Patients older than 50 years-old and newly diagnosed with thyroid cancer between 2000 and 2008 were identified from the national health insurance research database (NHIRD). We applied time-varying Cox proportional hazard models to assess the association between thyroid cancer and AMD. The multivariable models included conventional cardiovascular risk factors, myopia, vitreous floaters, hypothyroidism, hyperthyroidism, and treatment modality of thyroid cancer. The analysis process was stratified by age, gender, and comorbidity. In this study, 5253 patients were included in a thyroid cancer cohort (men 24.5%; median age 59.1 years (53.7⁻67.4 years), and 21,012 matched controls were included in a non-thyroid cancer cohort. The AMD incidence was 40.7 per 10,000 person/year in the thyroid cancer cohort. The thyroid cancer cohort had a higher risk (adjusted hazard ratio (aHR) = 1.38, 95% confidence interval, CI = 1.09⁻1.75) of AMD than the non-thyroid cohort. Thyroid cancer patients had a higher risk of AMD, especially the male patients (aHR = 1.92, 95% CI = 1.38⁻3.14) and the patients with comorbidities (aHR = 1.38, 95% CI = 1.09⁻1.74). In conclusion, thyroid cancer patients older than 50 years-old have increased risk of AMD.

[AMD Annals: a model of continuous monitoring and improvement of the quality of diabetes care].

PubMed

2011-01-01

in recent years, several initiatives have been launched by the Associazione medici diabetologi (AMD) in the context of a national quality improvement program.These activities include: identification of specific indicators of quality of diabetes care, development of a software to calculate such indicators by using routine clinical data, creation of a network of diabetes clinics and analysis and publication of the results in ad hoc reports (AMD Annals). Through the best performer approach, each centre could compare its own performance not only with the theoretical targets suggested by existing guidelines, but also with the results achieved by the best centres operating within the same healthcare system.We evaluated whether the involvement of diabetes clinics into the AMD Annals initiative improved the quality of care over 4 years. a controlled before and after study was performed to compare data collected from 2004 to 2007 by two groups of centres: group A included centres that had been involved in the project since the first edition of AMD Annals; group B included centres only involved in the last edition. overall, 124 diabetes clinics provided data on over 100,000 type 2 diabetes patients/year seen from 2004 to 2007. process indicators included the proportion of patients with at least one measurement of HbA1c, blood pressure and lipid profile during the previous 12 months. Intermediate outcomes included percentages of patients with levels of HbA1c ≤ 7%, blood pressure ≤ 130/85 mmHg and LDL-cholesterol <100 mg/dl (favourable indicators), and the percentages of patients with levels of HbA1c ≥ 9%, blood pressure ≥ 140/90 mmHg and LDL-cholesterol ≥ 130 mg/dl (unfavourable indicators). Percentages of patients treated with insulin, two or more antihypertensive agents, and statins were also evaluated. A multilevel analysis adjusted for age, gender, diabetes duration, and clustering effect was applied to investigate the changes in the indicators between the two groups of centres during 4 years. lipid profile monitoring increased more in group A (+6.2% from 2004 to 2007) than in group B (+2.4%), while HbA1c and blood pressure monitoring did not change over time in both groups. As for the outcomes considered, the percentage of patients with HbA1c ≤ 7% increased by 6% in group A and by 1.3%in group B, while the proportion of patients achieving the blood pressure target increased in group A (+6.4%), but not in group B (-1.4%). A reduction in the percentage of patients with blood pressure ≥ 140/90 mmHg was found in group A (-7.3%) but not in group B (-0.9%). Marked improvements in the proportion of patients with LDL-cholesterol at target were documented in both groups (group A: +10.5%; group B: +12.2%.) The proportion of patients treated with insulin increased in group A only (+5.8%), while the use of statins grew by 20%in both groups.The proportion of individuals treated with two or more antihypertensive drugs increased by 3.6% in group A and by 1.6% in group B. the AMD Annals approach can be considered as a case model for quality improvement activities in chronic diseases and a tool to evaluate the level of adoption/acceptance of guidelines in clinical practice. The considerable success documented was obtained without allocation of extra resources or financial incentives but simply through a physician-led effort made possible by the commitment of the specialists involved.

Automated detection of exudative age-related macular degeneration in spectral domain optical coherence tomography using deep learning.

PubMed

Treder, Maximilian; Lauermann, Jost Lennart; Eter, Nicole

2018-02-01

Our purpose was to use deep learning for the automated detection of age-related macular degeneration (AMD) in spectral domain optical coherence tomography (SD-OCT). A total of 1112 cross-section SD-OCT images of patients with exudative AMD and a healthy control group were used for this study. In the first step, an open-source multi-layer deep convolutional neural network (DCNN), which was pretrained with 1.2 million images from ImageNet, was trained and validated with 1012 cross-section SD-OCT scans (AMD: 701; healthy: 311). During this procedure training accuracy, validation accuracy and cross-entropy were computed. The open-source deep learning framework TensorFlow™ (Google Inc., Mountain View, CA, USA) was used to accelerate the deep learning process. In the last step, a created DCNN classifier, using the information of the above mentioned deep learning process, was tested in detecting 100 untrained cross-section SD-OCT images (AMD: 50; healthy: 50). Therefore, an AMD testing score was computed: 0.98 or higher was presumed for AMD. After an iteration of 500 training steps, the training accuracy and validation accuracies were 100%, and the cross-entropy was 0.005. The average AMD scores were 0.997 ± 0.003 in the AMD testing group and 0.9203 ± 0.085 in the healthy comparison group. The difference between the two groups was highly significant (p < 0.001). With a deep learning-based approach using TensorFlow™, it is possible to detect AMD in SD-OCT with high sensitivity and specificity. With more image data, an expansion of this classifier for other macular diseases or further details in AMD is possible, suggesting an application for this model as a support in clinical decisions. Another possible future application would involve the individual prediction of the progress and success of therapy for different diseases by automatically detecting hidden image information.

Cholesterol in the retina: the best is yet to come

PubMed Central

Pikuleva, Irina A.; Curcio, Christine A.

2014-01-01

Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes’ roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. PMID:24704580

Stable sulfur and oxygen isotopes as geochemical tracers of sulfate in karst waters

NASA Astrophysics Data System (ADS)

Sun, Jing; Kobayashi, Tatsuaki; Strosnider, William H. J.; Wu, Pan

2017-08-01

Karst water resources, which are extremely sensitive to mining activities, are critical for the support of human societies and ecological systems in many regions worldwide. In order to determine the sources and fate of dissolved sulfate in low-pH karst waters, hydrochemical variations of karst waters with and without acid mine drainage (AMD) impacts were investigated along with stable isotope dynamics. As expected, hydrochemical characteristics and isotopic compositions of the AMD and AMD-downstream water (ADW) were dramatically different from that of the non-AMD-impacted water (NAW). The sources of sulfur isotopes in sulfate were predominantly pyrite oxidation for the AMD and ADW, and atmospheric deposition for the NAW. Based on the general isotope-balance model, the relative proportions of sulfate oxygen derived from water and air were calculated. The mean proportion of sulfate oxygen derived from water in ADW was roughly double that of AMD. This suggests that the sulfate associated with AMD is predominantly influenced by aerobic pyrite oxidation, while that of ADW is likely affected by the dissolution of pyrite under anaerobic conditions in reservoir sediment. This observation was coincident with the noted variations of hydrochemical characteristics and was supported by principal component analysis. These results provide a better understanding of how stable isotopes of sulfate and water can be used to track mining contamination in karst aquifers, which could benefit remediation planning for these distinctive systems.

The association between statin use and risk of age-related macular degeneration

PubMed Central

Ma, Le; Wang, Yafeng; Du, Junhui; Wang, Mingxu; Zhang, Rui; Fu, Yihao

2015-01-01

The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74–1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66–0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80–0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77–1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention. PMID:26658620

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PubMed

Itakura, Katsumasa; Takahashi, Ikuno; Nakashima, Eiji; Yanagi, Masahide; Kawasaki, Ryo; Neriishi, Kazuo; Wang, Jie Jin; Wong, Tien Yin; Hida, Ayumi; Ohishi, Waka; Kiuchi, Yoshiaki

2015-08-01

To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

Past physical activity and age-related macular degeneration: the Melbourne Collaborative Cohort Study.

PubMed

McGuinness, Myra B; Karahalios, Amalia; Simpson, Julie A; Guymer, Robyn H; Robman, Luba D; Hodge, Allison M; Cerin, Ester; Giles, Graham G; Finger, Robert P

2016-10-01

To assess the association between past physical activity and early, intermediate and late age-related macular degeneration (AMD) in a community-based cohort study in Melbourne, Australia. Diet and lifestyle information was recorded at baseline (1990-1994) and total recreational activity was derived from walking, vigorous and non-vigorous exercise. At follow-up (2003-2007), digital macular photographs were graded for early, intermediate and late AMD. Data were analysed using multinomial logistic regression controlling for age, sex, smoking, region of descent, diet and alcohol. Effect modification by sex was investigated. Out of 20 816 participants, early, intermediate and late AMD were detected at follow-up in 4244 (21%), 2661 (13%) and 122 (0.6%) participants, respectively. No association was detected between past total recreational physical activity and early, intermediate or late AMD. Frequent (≥3 times/week) and less frequent (1-2 times/week) vigorous exercise were associated with lower odds of intermediate and late AMD in univariable models. After controlling for confounders, there was evidence of effect modification by sex and frequent vigorous exercise was associated with a 22% decrease in the odds of intermediate AMD (95% CI 4% to 36%) in women, but no association was found for men. Past frequent vigorous exercise may be inversely related to the presence of intermediate AMD in women. Further studies are needed to confirm whether physical activity and exercise have a protective effect for AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Peripheral Retinal Changes Associated with Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 12 by the Age-Related Eye Disease Study 2 Optos PEripheral RetinA (OPERA) Study Research Group.

PubMed

Domalpally, Amitha; Clemons, Traci E; Danis, Ronald P; Sadda, SriniVas R; Cukras, Catherine A; Toth, Cynthia A; Friberg, Thomas R; Chew, Emily Y

2017-04-01

To compare rates of peripheral retinal changes in Age-Related Eye Disease Study 2 (AREDS2) participants with at least intermediate age-related macular degeneration (AMD) with control subjects without intermediate age-related changes (large drusen). Cross-sectional evaluation of clinic-based patients enrolled in AREDS2 and a prospective study. Participants from prospective studies. The 200° pseudocolor and fundus autofluorescence (FAF) images were captured on the Optos 200 Tx Ultrawide-field device (Optos, Dunfermline, Scotland) by centering on the fovea and then steering superiorly and inferiorly. The montaged images were graded at a reading center with the images divided into 3 zones (zone 1 [posterior pole], zone 2 [midperiphery], and zone 3 [far periphery]) to document the presence of peripheral lesions. Peripheral retinal lesions: drusen, hypopigmentary/hyperpigmentary changes, reticular pseudodrusen, senile reticular pigmentary changes, cobblestone degeneration, and FAF abnormalities. A total of 484 (951 eyes) AREDS2 participants with AMD (cases) and 89 (163 eyes) controls without AMD had gradable color and FAF images. In zones 2 and 3, neovascularization and geographic atrophy (GA) were present, ranging from 0.4% to 6% in eyes of cases, respectively, and GA was present in 1% of eyes of controls. Drusen were detected in 97%, 78%, and 64% of eyes of cases and 48%, 21%, and 9% of eyes of controls in zones 2 and 3 superior and 3 inferior, respectively (P < 0.001 for all). Peripheral reticular pseudodrusen were seen in 15%. Senile reticular pigmentary change was the predominant peripheral change seen in 48% of cases and 16% of controls in zone 2 (P < 0.001). Nonreticular pigment changes were less frequent in the periphery than in the posterior pole (46% vs. 76%) and negligible in controls. Peripheral retinal changes are more prevalent in eyes with AMD than in control eyes. Drusen are seen in a majority of eyes with AMD in both the mid and far periphery, whereas pigment changes and features of advanced AMD are less frequent. Age-related macular degeneration may be more than a "macular" condition but one that involves the entire retina. Future longitudinal studies of peripheral changes in AMD and their impact on visual function may contribute to understanding AMD pathogenesis. Published by Elsevier Inc.

VALUING ACID MINE DRAINAGE REMEDIATION IN WEST VIRGINIA: A HEDONIC MODELING APPROACH

EPA Science Inventory

States with active and abandoned mines face large private and public costs to remediate damage to streams and rivers from acid mine drainage (AMD). Appalachian states have an especially large number of contaminated streams and rivers, and the USGS places AMD as the primary source...

[⁹⁹mTc]O₂-AMD3100 as a SPECT tracer for CXCR4 receptor imaging.

PubMed

Hartimath, Siddesh V; Domanska, Urszula M; Walenkamp, Annemiek M E; Rudi A J O, Dierckx; de Vries, Erik F J

2013-05-01

CXCR4 plays an important role in HIV infection, tumor progression, neurogenesis, and inflammation. In-vivo imaging of CXCR4 could provide more insight in the role of this receptor in health and disease. The aim of this study was to investigate [(99m)Tc]O₂-AMD3100 as a potential SPECT tracer for imaging of CXCR4. AMD3100 was labelled with [(99m)Tc]pertechnetate. A cysteine challenge assay was performed to test the tracer stability. Heterologous and homologous receptor binding assay and internalization assay were performed in CXCR4 expressing Jurkat-T cells. Ex vivo biodistribution was studied in healthy mice at 30, 60, and 120 min after tracer injection. Tumor uptake of the tracer was determined by microSPECT imaging in nude mice xenografted with human PC-3 prostate tumor. Specificity of tracer uptake was determined by blocking studies using an excess of unlabelled AMD3100. AMD3100 was labelled with technetium-99m with a radiochemical yield of >98%. The tracer was stable in PBS and mouse plasma for at least 6h at 37 °C. Heterologous and homologous binding assays with AMD3100 showed IC50 values of 240 ± 10 μM, and 92 ± 5 μM for [(125)I]SDF-1α and [(99m)Tc]O₂-AMD3100 respectively, with negligible receptor internalisation. The tracer showed high uptake in liver, lungs, spleen, thymus, intestine and bone. Blocking dose of AMD3100.8HCl (20mg/kg) decreased the uptake in these organs (p<0.05). [(99m)Tc]O2-AMD3100 showed specific tumor accumulation in mice bearing PC-3 xenografts model. Time activity curves (TAC) in AMD3100 pre-treated animals tracer showed 1.7 times less tumor uptake as compared to control animals (p<0.05). [(99m)Tc]O2-AMD3100 is readily labelled, is stable in plasma and displays a favourable binding affinity for the CXCR4 receptors. [(99m)Tc O₂-AMD3100 shows specific binding in organs with high CXCR4 expression and in CXCR4 positive tumors. These results justify further evaluation of this radiopharmaceutical as a potential biomarker for the non-invasive imaging of CXCR4 receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration.

PubMed

Woo, Se Joon; Ahn, Jeeyun; Morrison, Margaux A; Ahn, So Yeon; Lee, Jaebong; Kim, Ki Woong; DeAngelis, Margaret M; Park, Kyu Hyung

2015-01-01

To investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD). A total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed. Age, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p<.05 for all). Four SNPs, ARMS2/HTRA1 rs10490924, rs11200638, and rs2736911, and CFH rs800292, showed association with exudative AMD. Two of these SNPs, ARMS2/HTRA1 rs10490924 and rs11200638, showed significant association with typical CNV and PCV specifically. There were no significant interactions between environmental and genetic factors. The most predictive disease model for exudative AMD included age, spherical equivalent, smoking, CFH rs800292, and ARMS2 rs10490924 while that for typical CNV included age, hyperlipidemia, spherical equivalent, and ARMS2 rs10490924. Smoking, spherical equivalent, and ARMS2 rs10490924 were the most predictive variables for PCV. When comparing PCV cases to CNV cases, age, BMI, and education were the most predictive risk factors of PCV. Only one locus, the ARMS2/HTRA1 was a significant genetic risk factor for Korean exudative AMD, including its subtypes, PCV and typical CNV. Stepwise regression revealed that CFH was important to risk of exudative AMD in general but not to any specific subtype. While increased education was a unique risk factor to PCV when compared to CNV, this association was independent of refractive error in this homogenous population from South Korea. No significant interactions between environmental and genetic risk factors were observed.

Evaluation of real-world mobility in age-related macular degeneration.

PubMed

Sengupta, Sabyasachi; Nguyen, Angeline M; van Landingham, Suzanne W; Solomon, Sharon D; Do, Diana V; Ferrucci, Luigi; Friedman, David S; Ramulu, Pradeep Y

2015-01-30

Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility. Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accelerometers and cellular network-based tracking devices over 7 days of normal activity. Number of steps taken, time spent in moderate-to-vigorous physical activity (MVPA), number of excursions from home, and time spent away from home were the primary outcome measures. In multivariate negative binomial regression models adjusted for age, gender, race, comorbidities, and education, AMD participants took fewer steps than controls (18% fewer steps per day, p = 0.01) and spent significantly less time in MVPA (35% fewer minutes, p < 0.001). In multivariate logistic regression models adjusting for age, sex, race, cognition, comorbidities, and grip strength, AMD subjects showed an increased likelihood of not leaving their home on a given day (odds ratio = 1.36, p = 0.04), but did not show a significant difference in the magnitude of time spent away from home (9% fewer minutes, p = 0.11). AMD patients with poorer vision engage in significantly less physical activity and take fewer excursions away from the home. Further studies identifying the factors mediating the relationship between vision loss and mobility are needed to better understand how to improve mobility among AMD patients.

The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease

PubMed Central

Sidman, Richard L.; Li, Jianxue; Lawrence, Matthew; Hu, Wenzheng; Musso, Gary F.; Giordano, Ricardo J.; Cardó-Vila, Marina; Pasqualini, Renata; Arap, Wadih

2016-01-01

Blood vessel growth from preexisting vessels (angiogenesis) underlies many severe diseases including major blinding retinal diseases such as retinopathy of prematurity (ROP) and aged macular degeneration (AMD). This observation has driven development of antibody inhibitors that block a central factor in AMD, named vascular endothelial growth factor (VEGF), from binding to its receptors VEGFR-1 and VEGFR-2. However, some patients are insensitive to current anti-VEGF drugs or develop resistance, and the required repeated intravitreal injection of these large molecules is costly and clinically problematic. Here, we have evaluated a small cyclic retro-inverted peptidomimetic, D(Cys-Leu-Pro-Arg-Cys), abbreviated as D(CLPRC), and hereafter named Vasotide, that inhibits retinal angiogenesis by binding selectively to the VEGF receptors, VEGFR-1 and Neuropilin-1 (NRP-1). Delivery of Vasotide in eye drops or via intraperitoneal injection in a laser-induced monkey model of human wet AMD, a mouse genetic knockout model of the AMD subtype called retinal angiomatous proliferation (RAP), and a mouse oxygen-induced model of retinopathy of prematurity (ROP) markedly decreased retinal angiogenesis in all three animal models. This prototype drug candidate is a promising new dual receptor inhibitor of the VEGF ligand with potential for translation into safer, less invasive applications to combat pathological angiogenesis in retinal disorders. PMID:26468327

Isobaric yield ratio difference between the 140 A MeV 58Ni + 9Be and 64Ni +9Be reactions studied by the antisymmetric molecular dynamics model

NASA Astrophysics Data System (ADS)

Qiao, C. Y.; Wei, H. L.; Ma, C. W.; Zhang, Y. L.; Wang, S. S.

2015-07-01

Background: The isobaric yield ratio difference (IBD) method is found to be sensitive to the density difference of neutron-rich nucleus induced reaction around the Fermi energy. Purpose: An investigation is performed to study the IBD results in the transport model. Methods: The antisymmetric molecular dynamics (AMD) model plus the sequential decay model gemini are adopted to simulate the 140 A MeV 58 ,64Ni +9Be reactions. A relative small coalescence radius Rc= 2.5 fm is used for the phase space at t = 500 fm/c to form the hot fragment. Two limitations on the impact parameter (b 1 =0 -2 fm and b 2 =0 -9 fm) are used to study the effect of central collisions in IBD. Results: The isobaric yield ratios (IYRs) for the large-A fragments are found to be suppressed in the symmetric reaction. The IBD results for fragments with neutron excess I = 0 and 1 are obtained. A small difference is found in the IBDs with the b 1 and b 2 limitations in the AMD simulated reactions. The IBD with b 1 and b 2 are quite similar in the AMD + GEMINI simulated reactions. Conclusions: The IBDs for the I =0 and 1 chains are mainly determined by the central collisions, which reflects the nuclear density in the core region of the reaction system. The increasing part of the IBD distribution is found due to the difference between the densities in the peripheral collisions of the reactions. The sequential decay process influences the IBD results. The AMD + GEMINI simulation can better reproduce the experimental IBDs than the AMD simulation.

VALUING ACID MINE DRAINAGE REMEDIATION OF IMPAIRED WATERWAYS IN WEST VIRGINIA: A HEDONIC MODELING APPROACH

EPA Science Inventory

States with active and abandoned mines face large private and public costs to remediate damage to streams and rivers from acid mine drainage (AMD), the metal rich runoff flowing primarily from abandoned mines and surface deposits of mine waste. AMD can lower stream and river pH ...

VALUING ACID MINE DRAINAGE REMEDIATION IN WEST VIRGINIA: A HEDONIC MODELING APPROACH INCORPORATING GEOGRAPHIC INFORMATION SYSTEMS

EPA Science Inventory

States with active and abandoned mines face large private and public costs to remediate damage to streams and rivers from acid mine drainage (AMD). Appalachian states have an especially large number of contaminated streams and rivers, and the USGS places AMD as the primary source...

Acid neutralization within limestone sand reactors receiving coal mine drainage

USGS Publications Warehouse

Watten, B.J.; Sibrell, P.L.; Schwartz, M.F.

2005-01-01

Pulsed bed treatment of acid mine drainage (AMD) uses CO2 to accelerate limestone dissolution and intermittent fluidization to abrade and carry away metal hydrolysis products. Tests conducted with a prototype of 60 L/min capacity showed effective removal of H+ acidity over the range 196-584 mg/L (CaCO3) while concurrently generating surplus acid neutralization capacity. Effluent alkalinity (mg/L CaCO3) rose with increases in CO2 (DC, mg/L) according to the model Alkalinity = 31.22 + 2.97(DC)0.5, where DC was varied from 11-726 mg/L. Altering fluidization and contraction periods from 30 s/30 s to 10 s/50 s did not influence alkalinity but did increase energy dissipation and bed expansion ratios. Field trials with three AMD sources demonstrated the process is capable of raising AMD pH above that required for hydrolysis and precipitation of Fe3+ and Al3+ but not Fe2+ and Mn2+. Numerical modeling showed CO2 requirements are reduced as AMD acidity increases and when DC is recycled from system effluent. ?? 2005 Elsevier Ltd. All rights reserved.

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration123

PubMed Central

Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

2017-01-01

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress–related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n–3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. PMID:28096126

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration.

PubMed

Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

2017-01-01

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress-related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n-3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. © 2017 American Society for Nutrition.

Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium.

PubMed

Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

2014-09-01

To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Meta-analysis. setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD. The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

Orthostatic hypertension as a risk factor for age-related macular degeneration: Evidence from the Irish longitudinal study on ageing.

PubMed

Bhuachalla, Bláithín Ní; McGarrigle, Christine A; O'Leary, Neil; Akuffo, Kwadwo Owusu; Peto, Tunde; Beatty, Stephen; Kenny, Rose Anne

2018-06-01

Age related macular degeneration (AMD) is a leading cause of irreversible visual loss in developed countries. It is associated with vascular risk factors including hypertension. Dysregulated blood pressure (BP) behaviour including orthostatic hypertension (OHTN), hypotension (OH) and BP variability (BPV) are associated with end-organ damage, particularly in the brain. We investigated if abnormal orthostatic BP (OBP) was a risk factor for AMD, for which a vascular aetiology is implicated. A nationally representative, cross-sectional study was carried out 2009/2010 in The Irish Longitudinal Study on Ageing (TILDA). Beat-to-beat BP data, measured by digital photoplethysmography during active stand, was used to characterise OBP behaviour in the 30-110 s after standing. OH, OHTN, BPV and normal stabilisation recovery phenotypes were defined. AMD was identified following masked grading of 45° monoscopic colour retinal photographs, which were centred on the macula and taken with a NIDEK AFC-210 non-mydriatic auto-fundus camera. The relationship between OBP recovery phenotypes and AMD in 3750 adults aged ≥50 years was investigated using multivariate logistic regression models, adjusted for traditional AMD risk factors. From 30 to 110 s post active stand, systolic and diastolic OHTN was associated with increased odds of AMD after adjustment for demographics, health behaviours including smoking, family history of AMD, self-report (SR) diabetes, SR cataracts, objective hypertension and prescribed antihypertensives. No evidence of heterogeneity of OHTN effect was found between those who were hypertensive to those who were normotensive. This study provides evidence that OHTN may be an independent cardiovascular risk factor for AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

ABSORPTION MEASURE DISTRIBUTION IN Mrk 509

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adhikari, T. P.; Różańska, A.; Sobolewska, M.

2015-12-20

In this paper we model the observed absorption measure distribution (AMD) in Mrk 509, which spans three orders of magnitude in ionization level with a single-zone absorber in pressure equilibrium. AMD is usually constructed from observations of narrow absorption lines in radio-quiet active galaxies with warm absorbers. We study the properties of the warm absorber in Mrk 509 using recently published broadband spectral energy distribution observed with different instruments. This spectrum is an input in radiative transfer computations with full photoionization treatment using the titan code. We show that the simplest way to fully reproduce the shape of AMD is tomore » assume that the warm absorber is a single zone under constant total pressure. With this assumption, we found theoretical AMD that matches the observed AMD determined on the basis of the 600 ks reflection grating spectrometer XMM-Newton spectrum of Mrk 509. The softness of the source spectrum and the important role of the free–free emission breaks the usual degeneracy in the ionization state calculations, and the explicit dependence of the depths of AMD dips on density open a new path to the density diagnostic for the warm absorber. In Mrk 509, the implied density is of the order of 10{sup 8} cm{sup −3}.« less

Generation of Transplantable Retinal Pigmented Epithelial (RPE) Cells for Treatment of Age-Related Macular Degeneration (AMD).

PubMed

Surendran, Harshini; Rathod, Reena J; Pal, Rajarshi

2018-06-13

Age-related macular degeneration (AMD) is the foremost cause of blindness in people over the age of 60 worldwide. Clinically, this disease starts with distortion in central vision eventually leading to legal blindness. Vision loss has a significant impact on quality of life and incurs a substantial cost to the economy. Furthermore, AMD is a complex and progressive neurodegenerative disorder that triggers visual impairment due to the loss of retinal pigmented epithelium (RPE) and the light-sensitive photoreceptors that they support, protect and provide nutrition. Currently, there is no curative treatment for the most common form of this disease, i.e., dry AMD. A novel approach to treat AMD involves the transplantation of RPE cells derived from human induced pluripotent stem cells (iPSCs) in the outer retina. These iPSC-derived RPE cells not only show characteristics similar to native RPE but also could replace as well as regenerate damaged pathologic RPE and produce supportive growth factors and cytokines. Several clinical trials are being conducted taking advantage of a variety of cell- and tissue engineering-based approaches. Here, we present a simple, cost effective, and scalable cell-culture model for generation of purified RPE thus providing the foundation for developing an allogeneic cell therapy for AMD.

The reduction of serum soluble Flt-1 in patients with neovascular age-related macular degeneration.

PubMed

Uehara, Hironori; Mamalis, Christina; McFadden, Molly; Taggart, Michael; Stagg, Brian; Passi, Samuel; Earle, Phillip; Chakravarthy, Usha; Hogg, Ruth E; Ambati, Balamurali K

2015-01-01

To evaluate serum soluble Flt-1 (sFlt-1) in age-related macular degeneration (AMD) patients. Case-control study. Study involved 56 non-AMD participants, 53 early AMD patients, and 97 neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS. Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8 ± 2.9 pg/mL (± standard error of the mean), 88.2 ± 2.6 pg/mL, and 79.9 ± 2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, P < .01). For each 10-point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decrease by 27.8%, odds ratio (OR) = 0.722 (95% confidence interval [CI]: 0.588-0.888, P = .002) and 27.0%, OR = 0.730 (95% CI: 0.594-0.898, P = .003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD. Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD. Copyright © 2015 Elsevier Inc. All rights reserved.

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration: A Novel Regression Analysis to Capture the Bilateral Nature of the Disease.

PubMed

Hodgson, Robert; Reason, Timothy; Trueman, David; Wickstead, Rose; Kusel, Jeanette; Jasilek, Adam; Claxton, Lindsay; Taylor, Matthew; Pulikottil-Jacob, Ruth

2017-10-01

The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. Novartis Pharmaceuticals UK Limited.

Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up.

PubMed

Wu, Juan; Cho, Eunyoung; Willett, Walter C; Sastry, Srinivas M; Schaumberg, Debra A

2015-12-01

Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated. To investigate the associations between intakes of carotenoids and AMD. Prospective cohort study, with cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study in the United States. A total of 63,443 women and 38,603 men were followed up, from 1984 until May 31, 2010, in the Nurses' Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline. Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined. We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend < .001). Predicted plasma carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend < .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD. Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.

Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD).

PubMed

Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

2016-12-08

The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

Acid mine drainage

USGS Publications Warehouse

Bigham, Jerry M.; Cravotta, Charles A.

2016-01-01

Acid mine drainage (AMD) consists of metal-laden solutions produced by the oxidative dissolution of iron sulfide minerals exposed to air, moisture, and acidophilic microbes during the mining of coal and metal deposits. The pH of AMD is usually in the range of 2–6, but mine-impacted waters at circumneutral pH (5–8) are also common. Mine drainage usually contains elevated concentrations of sulfate, iron, aluminum, and other potentially toxic metals leached from rock that hydrolyze and coprecipitate to form rust-colored encrustations or sediments. When AMD is discharged into surface waters or groundwaters, degradation of water quality, injury to aquatic life, and corrosion or encrustation of engineered structures can occur for substantial distances. Prevention and remediation strategies should consider the biogeochemical complexity of the system, the longevity of AMD pollution, the predictive power of geochemical modeling, and the full range of available field technologies for problem mitigation.

Note: Development of a small maglev-type antirolling system.

PubMed

Park, Cheol Hoon; Park, Hee Chang; Cho, Han Wook; Moon, Seok Jun; Chung, Tae Young

2010-05-01

Various passive and/or active antirolling devices have been used for suppressing the rolling motion of ships in the ocean. In this study, a maglev-type active mass driver (AMD) is developed for controlling the rolling motion of a shiplike structure. No friction is generated during the motion of this maglev-type AMD, as the moving mass is floated by the magnetic levitation force and displaced by the propulsion force generated by the linear motor. For verifying the feasibility of the proposed method, a small AMD having a moving mass of approximately 4.0 kg is constructed and used in a small-scale model of a catamaran. This paper presents the detailed design procedures and obtained experimental results. Our results show that the developed maglev-type AMD has the potential for use in controlling the rolling motion of ships and other oceanographic vessels.

Cluster correlation and fragment emission in 12C+12C at 95 MeV/nucleon

NASA Astrophysics Data System (ADS)

Tian, G.; Chen, Z.; Han, R.; Shi, F.; Luo, F.; Sun, Q.; Song, L.; Zhang, X.; Xiao, G. Q.; Wada, R.; Ono, A.

2018-03-01

The impact of cluster correlations has been studied in the intermediate mass fragment (IMF) emission in 12C+12C at 95 MeV/nucleon, using antisymmetrized molecular dynamics (AMD) model simulations. In AMD, the cluster correlation is introduced as a process to form light clusters with A ≤4 in the final states of a collision induced by the nucleon-nucleon residual interaction. Correlations between light clusters are also considered to form light nuclei with A ≤9 . This version of AMD, combined with GEMINI to calculate the decay of primary fragments, reproduces the experimental energy spectra of IMFs well overall with reasonable reproduction of light charged particles when we carefully analyze the excitation energies of primary fragments produced by AMD and their secondary decays. The results indicate that the cluster correlation plays a crucial role for producing fragments at relatively low excitation energies in the intermediate-energy heavy-ion collisions.

Incorporating Geochemical And Microbial Kinetics In Reactive Transport Models For Generation Of Acid Rock Drainage

NASA Astrophysics Data System (ADS)

Andre, B. J.; Rajaram, H.; Silverstein, J.

2010-12-01

Acid mine drainage, AMD, results from the oxidation of metal sulfide minerals (e.g. pyrite), producing ferrous iron and sulfuric acid. Acidophilic autotrophic bacteria such as Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans obtain energy by oxidizing ferrous iron back to ferric iron, using oxygen as the electron acceptor. Most existing models of AMD do not account for microbial kinetics or iron geochemistry rigorously. Instead they assume that oxygen limitation controls pyrite oxidation and thus focus on oxygen transport. These models have been successfully used for simulating conditions where oxygen availability is a limiting factor (e.g. source prevention by capping), but have not been shown to effectively model acid generation and effluent chemistry under a wider range of conditions. The key reactions, oxidation of pyrite and oxidation of ferrous iron, are both slow kinetic processes. Despite being extensively studied for the last thirty years, there is still not a consensus in the literature about the basic mechanisms, limiting factors or rate expressions for microbially enhanced oxidation of metal sulfides. An indirect leaching mechanism (chemical oxidation of pyrite by ferric iron to produce ferrous iron, with regeneration of ferric iron by microbial oxidation of ferrous iron) is used as the foundation of a conceptual model for microbially enhanced oxidation of pyrite. Using literature data, a rate expression for microbial consumption of ferrous iron is developed that accounts for oxygen, ferrous iron and pH limitation. Reaction rate expressions for oxidation of pyrite and chemical oxidation of ferrous iron are selected from the literature. A completely mixed stirred tank reactor (CSTR) model is implemented coupling the kinetic rate expressions, speciation calculations and flow. The model simulates generation of AMD and effluent chemistry that qualitatively agrees with column reactor and single rock experiments. A one dimensional reaction diffusion model at the scale of a single rock is developed incorporating the proposed kinetic rate expressions. Simulations of initiation, washout and AMD flows are discussed to gain a better understanding of the role of porosity, effective diffusivity and reactive surface area in generating AMD. Simulations indicate that flow boundary conditions control generation of acid rock drainage as porosity increases.

Nitrogen Metabolism and Growth Enhancement in Tomato Plants Challenged with Trichoderma harzianum Expressing the Aspergillus nidulans Acetamidase amdS Gene

PubMed Central

Domínguez, Sara; Rubio, M. Belén; Cardoza, Rosa E.; Gutiérrez, Santiago; Nicolás, Carlos; Bettiol, Wagner; Hermosa, Rosa; Monte, Enrique

2016-01-01

Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in Trichoderma harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea, and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by (i) enhanced growth, (ii) increased carbon and nitrogen levels, and (iii) a higher sensitivity to B. cinerea infections in plants treated with amdS transformants as detected in greenhouse assays. These observations suggest that the increased plant development promoted by the amdS transformants was at expense of defenses. PMID:27536277

Nitrogen Metabolism and Growth Enhancement in Tomato Plants Challenged with Trichoderma harzianum Expressing the Aspergillus nidulans Acetamidase amdS Gene.

PubMed

Domínguez, Sara; Rubio, M Belén; Cardoza, Rosa E; Gutiérrez, Santiago; Nicolás, Carlos; Bettiol, Wagner; Hermosa, Rosa; Monte, Enrique

2016-01-01

Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in Trichoderma harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea, and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by (i) enhanced growth, (ii) increased carbon and nitrogen levels, and (iii) a higher sensitivity to B. cinerea infections in plants treated with amdS transformants as detected in greenhouse assays. These observations suggest that the increased plant development promoted by the amdS transformants was at expense of defenses.

Synthesising acid mine drainage to maintain and exploit indigenous mining micro-algae and microbial assemblies for biotreatment investigations.

PubMed

Orandi, Sanaz; Lewis, David M

2013-02-01

The stringent regulations for discharging acid mine drainage (AMD) has led to increased attention on traditional or emerging treatment technologies to establish efficient and sustainable management for mine effluents. To assess new technologies, laboratory investigations on AMD treatment are necessary requiring a consistent supply of AMD with a stable composition, thus limiting environmental variability and uncertainty during controlled experiments. Additionally, biotreatment systems using live cells, particularly micro-algae, require appropriate nutrient availability. Synthetic AMD (Syn-AMD) meets these requirements. However, to date, most of the reported Syn-AMDs are composed of only a few selected heavy metals without considering the complexity of actual AMD. In this study, AMD was synthesised based on the typical AMD characteristics from a copper mine where biotreatment is being considered using indigenous AMD algal-microbes. Major cations (Ca, Na, Cu, Zn, Mg, Mn and Ni), trace metals (Al, Fe, Ag, Na, Co, Mo, Pb and Cr), essential nutrients (N, P and C) and high SO(4) were incorporated into the Syn-AMD. This paper presents the preparation of chemically complex Syn-AMD and the challenges associated with combining metal salts of varying solubility that is not restricted to one particular mine site. The general approach reported and the particular reagents used can produce alternative Syn-AMD with varying compositions. The successful growth of indigenous AMD algal-microbes in the Syn-AMD demonstrated its applicability as appropriate generic media for cultivation and maintenance of mining microorganisms for future biotreatment studies.

IMPROVING THE AGE-RELATED MACULAR DEGENERATION CONSTRUCT: A New Classification System.

PubMed

Spaide, Richard F

2018-05-01

Previous models of disease in age-related macular degeneration (AMD) were incomplete in that they did not encompass subretinal drusenoid deposits (pseudodrusen), subtypes of neovascularization, and polypoidal choroidal vasculopathy. In addition, Type 3 neovascularization starts in the retina and may not necessarily involve the choroid. As such, the term choroidal neovascularization is not appropriate for these eyes. The new aspects in the AMD construct are to include specific lipoprotein extracellular accumulations, namely drusen and subretinal drusenoid deposits, as early AMD. The deposition of specific types of deposit seems to be highly correlated with choroidal thickness and topographical location in the macula. Late AMD includes macular neovascularization or atrophy. The particular type of extracellular deposit is predictive of the future course of the patient. For example, eyes with subretinal drusenoid deposits have a propensity to develop outer retinal atrophy, complete outer retinal and retinal pigment epithelial atrophy, or Type 3 neovascularization as specific forms of late AMD. Given Type 3 neovascularization may never involve the choroid, the term macular neovascularization is suggested for the entire spectrum of neovascular disease in AMD. In contrast to older classification systems, the proposed system encompasses the relevant presentations of disease and more precisely predicts the future course of the patient. In doing so, the concept was developed that there may be genetic risk alleles, which are not necessarily the same alleles that influence disease expression.

Natural History of Age-Related Retinal Lesions That Precede AMD in Mice Fed High or Low Glycemic Index Diets

PubMed Central

Weikel, Karen A.; FitzGerald, Paul; Shang, Fu; Caceres, M. Andrea; Bian, Qingning; Handa, James T.; Stitt, Alan W.

2012-01-01

Purpose. Epidemiologic data indicate that people who consume low glycemic index (GI) diets are at reduced risk for the onset and progression of age-related macular degeneration (AMD). The authors sought corroboration of this observation in an animal model. Methods. Five- and 16-month-old C57BL/6 mice were fed high or low GI diets until they were 17 and 23.5 months of age, respectively. Retinal lesions were evaluated by transmission electron microscopy, and advanced glycation end products (AGEs) were evaluated by immunohistochemistry. Results. Retinal lesions including basal laminar deposits, loss of basal infoldings, and vacuoles in the retinal pigment epithelium were more prevalent in the 23.5- than in the 17-month-old mice. Within each age group, consumption of a high GI diet increased the risk for lesions and the risk for photoreceptor abnormalities and accumulation of AGEs. Conclusions. Consuming high GI diets accelerates the appearance of age-related retinal lesions that precede AMD in mice, perhaps by increasing the deposition of toxic AGEs in the retina. The data support the hypothesis that consuming lower GI diets, or simulation of their effects with nutraceuticals or drugs, may protect against AMD. The high GI-fed C57BL/6 mouse is a new model of age-related retinal lesions that precede AMD and mimic the early stages of disease and may be useful for drug discovery. PMID:22205601

Macrophages Inhibit Neovascularization in a Murine Model of Age-Related Macular Degeneration

PubMed Central

Apte, Rajendra S; Richter, Jennifer; Herndon, John; Ferguson, Thomas A

2006-01-01

Background Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 y of age in at least three continents. Choroidal neovascularization (CNV) is the process by which abnormal blood vessels develop underneath the retina. CNV develops in 10% of patients with AMD but accounts for up to 90% of the blindness from AMD. Although the precise etiology of CNV in AMD remains unknown, the macrophage component of the inflammatory response, which has been shown to promote tumor growth and support atherosclerotic plaque formation, is thought to stimulate aberrant angiogenesis in blinding eye diseases. The current theory is that macrophage infiltration promotes the development of neovascularization in CNV. Methods and Findings We examined the role of macrophages in a mouse model of CNV. IL-10 −/− mice, which have increased inflammation in response to diverse stimuli, have significantly reduced CNV with increased macrophage infiltrates compared to wild type. Prevention of macrophage entry into the eye promoted neovascularization while direct injection of macrophages significantly inhibited CNV. Inhibition by macrophages was mediated by the TNF family death molecule Fas ligand (CD95-ligand). Conclusions Immune vascular interactions can be highly complex. Normal macrophage function is critical in controlling pathologic neovascularization in the eye. IL-10 regulates macrophage activity in the eye and is an attractive therapeutic target in order to suppress or inhibit CNV in AMD that can otherwise lead to blindness. PMID:16903779

Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration.

PubMed

Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

2015-11-01

Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of climate change on acid mine drainage generation and contaminant transport in water ecosystems of semi-arid and arid mining areas

NASA Astrophysics Data System (ADS)

Anawar, Hossain Md.

Disposal of untreated and treated mining wastes and tailings exerts a significant threat and hazard for environmental contamination including groundwater, surface water, wetlands, land, food chain and animals. In order to facilitate remediation techniques, it is important to understand the oxidation of sulfidic minerals, and the hydrolysis of the oxidation products that result in production of acid mine drainage (AMD), toxic metals, low pH, SO42- and Fe. This review has summarized the impacts of climate change on geochemical reactions, AMD generation, and water quality in semi-arid/arid mining environments. Besides this, the study included the effects of hydrological, seasonal and climate change on composition of AMD, contaminant transport in watersheds and restoration of mining sites. Different models have different types of limitations and benefits that control their adaptability and suitability of application in various mining environments. This review has made a comparative discussion of a few most potential and widely used reactive transport models that can be applied to simulate the effect of climate change on sulfide oxidation and AMD production from mining waste, and contaminant transport in surface and groundwater systems.

Role of long-chain and very-long-chain polyunsaturated fatty acids in macular degenerations and dystrophies

PubMed Central

Liu, Aihua; Lin, Yanhua; Terry, Ryan; Nelson, Kelly; Bernstein, Paul S

2014-01-01

Macular degeneration is a progressive, bilateral eye disorder that damages the macula of the human eye. The most common form of macular degeneration is age-related macular degeneration (AMD), which is the leading cause of irreversible blindness in people older than 50 years in developed countries. Autosomal dominant Stargardt disease-3 (STGD3) is an inherited macular dystrophy that has clinical features similar to dry AMD, but occurs at a much earlier age. It is caused by a mutation in the elongation of very-long-chain fatty acids-like 4 (ELOVL4) gene, which is responsible for encoding the elongase enzyme that converts shorter chain fatty acids into C28–C38 very long-chain polyunsaturated fatty acids (VLCPUFAs, total number of carbons ≥24). Diets rich in long-chain polyunsaturated fatty acids (LCPUFAs) have inverse associations with the progression of AMD and STGD3, and a deficiency in retinal LCPUFAs and VLCPUFAs has been detected in AMD retinas and STGD3 animal models. This article systematically summarizes the roles of LCPUFAs and VLCPUFAs in AMD and STGD3, and discusses future research directions. PMID:25324899

Modulation of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 Axis Enhances rhBMP-2-Induced Ectopic Bone Formation

PubMed Central

Wise, Joel K.; Sumner, Dale Rick

2012-01-01

Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cell-derived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (μCT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the μCT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD3100 and SDF-1 treatment to stimulate trafficking of MSCs to an ectopic implant site, in order to ultimately enhance rhBMP-2 induced long-term bone formation. PMID:22035136

The potential effect of population development, smoking and antioxidant supplementation on the future epidemiology of age-related macular degeneration in Switzerland.

PubMed

Bauer, P; Barthelmes, D; Kurz, M; Fleischhauer, J C; Sutter, F K

2008-05-01

Due to the predicted age shift of the population an increase in the number of patients with late AMD is expected. At present smoking represents the only modifiable risk factor. Supplementation of antioxidants in patients at risk is the sole effective pharmacological prevention. The aim of this study is to estimate the future epidemiological development of late AMD in Switzerland and to quantify the potential effects of smoking and antioxidants supplementation. The modelling of the future development of late AMD cases in Switzerland was based on a meta-analysis of the published data on AMD-prevalence and on published Swiss population development scenarios until 2050. Three different scenarios were compared: low, mean and high. The late AMD cases caused by smoking were calculated using the "population attributable fraction" formula and data on the current smoking habits of the Swiss population. The number of potentially preventable cases was estimated using the data of the Age-Related Eye Disease Study (AREDS). According to the mean population development scenario, late AMD cases in Switzerland will rise from 37 200 cases in 2005 to 52 500 cases in 2020 and to 93 200 cases in 2050. Using the "low" and the "high" scenarios the late AMD cases may range from 49 500 to 56 000 in 2020 and from 73 700 to 118 400 in 2050, respectively. Smoking is responsible for approximately 7 % of all late AMD cases, i. e., 2600 cases in 2005, 3800 cases in 2020, 6600 cases in 2050 ("mean scenario"). With future antioxidant supplementation to all patients at risk another 3100 cases would be preventable until 2020 and possibly 23 500 cases until 2050. Due to age shift in the population a 2.5-fold increase in late AMD cases until 2050 is expected, representing a socioeconomic challenge. Cessation of smoking and supplementation of antioxidants to all patients at risk has the potential to reduce this number. Unfortunately, public awareness is low. These data may support health-care providers and public opinion leaders when developing public education and prevention strategies.

Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration during Diabetic Retinopathy Screening.

PubMed

Chan, Christina K W; Gangwani, Rita A; McGhee, Sarah M; Lian, JinXiao; Wong, David S H

2015-11-01

To determine whether screening for age-related macular degeneration (AMD) during a diabetic retinopathy (DR) screening program would be cost effective in Hong Kong. We compared and evaluated the impacts of screening, grading, and vitamin treatment for intermediate AMD compared with no screening using a Markov model. It was based on the natural history of AMD in a cohort with a mean age of 62 years, followed up until 100 years of age or death. Subjects attending a DR screening program were recruited. A cost-effectiveness analysis was undertaken from a public provider perspective. It included grading for AMD using the photographs obtained for DR screening and treatment with vitamin therapy for those with intermediate AMD. The measures of effectiveness were obtained largely from a local study, but the transition probabilities and utility values were from overseas data. Costs were all from local sources. The main assumptions and estimates were tested in sensitivity analyses. The outcome was cost per quality-adjusted life year (QALY) gained. Both costs and benefits were discounted at 3%. All costs are reported in United States dollars ($). The cost per QALY gained through screening for AMD and vitamin treatment for appropriate cases was $12,712 after discounting. This would be considered highly cost effective based on the World Health Organization's threshold of willingness to pay (WTP) for a QALY, that is, less than the annual per capita gross domestic product of $29,889. Because of uncertainty regarding the utility value for those with advanced AMD, we also tested an extreme, conservative value for utility under which screening remained cost effective. One-way sensitivity analyses revealed that, besides utility values, the cost per QALY was most sensitive to the progression rate from intermediate to advanced AMD. The cost-effectiveness acceptability curve showed a WTP for a QALY of $29,000 or more has a more than 86% probability of being cost effective compared with no screening. Our analysis demonstrated that AMD screening carried out simultaneously with DR screening for patients with diabetes would be cost effective in a Hong Kong public healthcare setting. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Assessing quality of life in the treatment of patients with age-related macular degeneration: clinical research findings and recommendations for clinical practice.

PubMed

Yuzawa, Mitsuko; Fujita, Kyoko; Tanaka, Erika; Wang, Edward C Y

2013-01-01

The importance of incorporating quality-of-life (QoL) assessments into medical practice is growing as health care practice shifts from a "disease-based" to a "patient-centered" model. The prevalence of age-related macular degeneration (AMD) is increasing in today's aging population. The purpose of this paper is: (1) to discuss, by reviewing the current literature, the impact of AMD on patients' QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2) to make a recommendation for incorporating QoL into clinical practice. We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected. AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA). QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients' valued activities, which are not captured by a single, numerical VA score. The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease-specific instruments for measuring QoL, such as the NEI VFQ-25, have shown a significant correlation of QoL decrement with measures of disease severity, as well as significant QoL improvement with treatment. The NEI VFQ-25 and other validated instruments provide a wide-ranging assessment of vision-related functioning that is important to patients and complementary to VA measurement. We strongly recommend the incorporation of QoL assessment into routine clinical practice.

Difference between age-related macular degeneration and polypoidal choroidal vasculopathy in the hereditary contribution of the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2).

PubMed

Yanagisawa, Suiho; Kondo, Naoshi; Miki, Akiko; Matsumiya, Wataru; Kusuhara, Sentaro; Tsukahara, Yasutomo; Honda, Shigeru; Negi, Akira

2011-01-01

To investigate whether the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2) has a different hereditary contribution in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). We initially conducted a comparative genetic analysis of neovascular AMD and PCV, genotyping the ARMS2 A69S variant in 181 subjects with neovascular AMD, 198 subjects with PCV, and 203 controls in a Japanese population. Genotyping was conducted using TaqMan technology. Results were then integrated into a meta-analysis of previous studies representing an assessment of the association between the ARMS2 A69S variant and neovascular AMD and/or PCV, comprising a total of 3,828 subjects of Asian descent. The Q-statistic test was used to assess between-study heterogeneity. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a fixed effects model. The genetic effect of the A69S variant was stronger in neovascular AMD (allelic summary OR=3.09 [95% CI, 2.71-3.51], fixed effects p<0.001) than in PCV (allelic summary OR=2.13 [95% CI, 1.91-2.38], fixed effects p<0.001). The pooled risk allele frequency was significantly higher in neovascular AMD (64.7%) than in PCV (55.6%). The population attributable risks for the variant allele were estimated to be 43.9% (95% CI, 39.0%-48.4%) and 29.7% (95% CI, 25.4%-34.0%) for neovascular AMD and PCV, respectively. No significant between-study heterogeneity was observed in any statistical analysis in this meta-analysis. Our meta-analysis provides substantial evidence that the ARMS2 A69S variant confers a significantly higher risk of neovascular AMD than PCV. Furthermore, there is compelling evidence that the risk attributable to the A69S variant differs between geographic atrophy and neovascular AMD. Together with defining the molecular basis of susceptibility, understanding the relationships between this genomic region and disease subtypes will yield important insights, elucidating the biologic architecture of this phenotypically heterogeneous disorder.

Lutein and Zeaxanthin—Food Sources, Bioavailability and Dietary Variety in Age-Related Macular Degeneration Protection

PubMed Central

Eisenhauer, Bronwyn; Natoli, Sharon; Liew, Gerald; Flood, Victoria M.

2017-01-01

Lutein and zeaxanthin (L/Z) are the predominant carotenoids which accumulate in the retina of the eye. The impact of L/Z intake on the risk and progression of age-related macular degeneration (AMD), a leading cause of blindness in the developed world, has been investigated in cohort studies and clinical trials. The aims of this review were to critically examine the literature and evaluate the current evidence relating to L/Z intake and AMD, and describe important food sources and factors that increase the bioavailability of L/Z, to inform dietary models. Cohort studies generally assessed L/Z from dietary sources, while clinical trials focused on providing L/Z as a supplement. Important considerations to take into account in relation to dietary L/Z include: nutrient-rich sources of L/Z, cooking methods, diet variety and the use of healthy fats. Dietary models include examples of how suggested effective levels of L/Z can be achieved through diet alone, with values of 5 mg and 10 mg per day described. These diet models depict a variety of food sources, not only from dark green leafy vegetables, but also include pistachio nuts and other highly bioavailable sources of L/Z such as eggs. This review and the diet models outlined provide information about the importance of diet variety among people at high risk of AMD or with early signs and symptoms of AMD. PMID:28208784

Genome-wide analysis of disease progression in age-related macular degeneration.

PubMed

Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

2018-03-01

Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen.

PubMed

Flamendorf, Jason; Agrón, Elvira; Wong, Wai T; Thompson, Darby; Wiley, Henry E; Doss, E Lauren; Al-Holou, Shaza; Ferris, Frederick L; Chew, Emily Y; Cukras, Catherine

2015-10-01

We investigate whether ocular and person-based characteristics were associated with dark adaptation (DA). Cross-sectional, single-center, observational study. One hundred sixteen participants older than 50 years of age with a range of age-related macular degeneration (AMD) severity. Participants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and was confirmed with optical coherence tomography. Eyes also were graded for AMD features (drusen, pigmentary changes, late AMD) to generate person-based AMD severity groups. One eye was designated the study eye for DA testing. Nonparametric statistical testing was performed on all comparisons. The primary outcome of this study was the rod intercept time (RIT), which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5×10(-3) cd/m(2) (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached. A total of 116 study eyes from 116 participants (mean age, 75.4±9.4 years; 58% female) were analyzed. Increased RIT was associated significantly with increasing AMD severity, increasing age (r = 0.34; P = 0.0002), decreasing BCVA (r = -0.54; P < 0.0001), pseudophakia (P = 0.03), and decreasing subfoveal choroidal thickness (r = -0.27; P = 0.003). Study eyes with RPD (15/116 [13%]) had a significantly greater mean RIT compared with eyes without RPD in any AMD severity group (P < 0.02 for all comparisons), with 80% reaching the DA test ceiling. Impairments in DA increased with age, worse visual acuity, presence of RPD, AMD severity, and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariate model that best fit the data included age, AMD group, and presence of RPD (R(2) = 0.56), with the presence of RPD conferring the largest parameter estimate. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Complement factor H Y402H variant and risk of age-related macular degeneration in Asians: a systematic review and meta-analysis.

PubMed

Kondo, Naoshi; Bessho, Hiroaki; Honda, Shigeru; Negi, Akira

2011-02-01

To investigate whether the Y402H variant in the complement factor H gene is associated with age-related macular degeneration (AMD) in Asian populations. Meta-analysis of previous publications. Case-control groups of subjects with AMD and controls from 13 association studies. We performed a meta-analysis of the association between Y402H and AMD in Asian populations using data available from 13 case-control studies involving 3973 subjects. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed- and random-effects models. The Q-statistic test was used to assess heterogeneity, and Egger's test was used to evaluate publication bias. Sensitivity analysis, cumulative meta-analysis, and meta-regression analysis were also performed. Allele and genotype frequencies of the Y402H variant. The Y402H variant showed a significant summary OR of 1.97 (95% CI, 1.54-2.52; P<0.001; allelic contrast model) per allele. Possession of at least 1 copy of the C allele increased the disease risk by 1.97-fold (95% CI, 1.63-2.39; P<0.001; dominant model) and accounted for 8.8% of the attributable risk of AMD in Asian populations. Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Meta-regression analysis indicated no significant effect of baseline study characteristics on the summary effect size. Cumulative meta-analysis revealed that the summary ORs were stable and the 95% CIs narrowed with the accumulation of data over time. Our analysis provides substantial evidence that the Y402H variant is significantly associated with AMD in Asian populations. Our results expand the number of confirmed AMD susceptibility loci for Asians populations, which provide a better understanding of the genetic architecture underlying disease susceptibility and may advance the potential for preclinical prediction in future genetic tests by a combined evaluation of inherited susceptibility with previously established loci. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Short-range correlation in high-momentum antisymmetrized molecular dynamics

NASA Astrophysics Data System (ADS)

Myo, Takayuki

2018-03-01

We propose a new variational method for treating short-range repulsion of bare nuclear force for nuclei in antisymmetrized molecular dynamics (AMD). In AMD, the short-range correlation is described in terms of large imaginary centroids of Gaussian wave packets of nucleon pairs in opposite signs, causing high-momentum components in the nucleon pairs. We superpose these AMD basis states and call this method "high-momentum AMD" (HM-AMD), which is capable of describing the strong tensor correlation [T. Myo et al., Prog. Theor. Exp. Phys., 2017, 111D01 (2017)]. In this letter, we extend HM-AMD by including up to two kinds of nucleon pairs in each AMD basis state utilizing the cluster expansion, which produces many-body correlations involving high-momentum components. We investigate how well HM-AMD describes the short-range correlation by showing the results for ^3H using the Argonne V4^' central potential. It is found that HM-AMD reproduces the results of few-body calculations and also the tensor-optimized AMD. This means that HM-AMD is a powerful approach to describe the short-range correlation in nuclei. In HM-AMD, the momentum directions of nucleon pairs isotropically contribute to the short-range correlation, which is different from the tensor correlation.

Interferon gamma-inducible protein-10 (IP-10) and eotaxin as biomarkers in age-related macular degeneration.

PubMed

Mo, Fong Ming; Proia, Alan D; Johnson, Walter H; Cyr, Desiree; Lashkari, Kameran

2010-08-01

To analyze serum cytokine levels in subjects with different stages of AMD and to study the expression of salient cytokines in postmortem eyes with AMD. A suspension array system was used to analyze sera (n = 18 to 20/group) from control subjects and those with early AMD (AREDS stage 1), intermediate dry AMD (AREDS stage 3), advanced AMD with geographic atrophy (GA), or neovascular AMD (CNV). Postmortem eyes with AMD or control eyes were examined immunohistochemically for expression of IP-10 and eotaxin (n = 4 to 8/group). Serum eotaxin and IP-10 levels were significantly elevated in all stages of AMD, except for eotaxin levels in neovascular AMD (P < 0.07). The peak of serum IP-10 concentration was at intermediate dry AMD. In donor eyes, IP-10 and eotaxin expressions were increased in the RPE of eyes with early AMD, GA, and CNV. Eotaxin accumulated within the layer of basal linear/laminar deposits in all stages of AMD, while IP-10 was mainly in eyes with GA and CNV. IP-10 was abundant in the connective tissue matrix associated with CNV, and eotaxin was usually present but more focally and with less intense staining. Both IP-10 and eotaxin were expressed by neovascular endothelial cells. Both IP-10 and eotaxin were expressed in the neurosensory retina, but there was no detectable difference in staining between eyes with or without AMD. IP-10 and eotaxin may be early biomarkers in AMD. The authors hypothesize that the relative balance between levels of IP-10 and eotaxin is critical in regulating the neovascular response.

AMD-like retinopathy associated with intravenous iron

PubMed Central

Song, Delu; Kanu, Levi N.; Li, Yafeng; Kelly, Kristen L.; Bhuyan, Rupak K.; Aleman, Tomas; Morgan, Jessica I. W.; Dunaief, Joshua L.

2016-01-01

Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (−Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls’ iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch’s membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas with high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch’s membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment. PMID:27565570

Electronic health record systems in ophthalmology: impact on clinical documentation.

PubMed

Sanders, David S; Lattin, Daniel J; Read-Brown, Sarah; Tu, Daniel C; Wilson, David J; Hwang, Thomas S; Morrison, John C; Yackel, Thomas R; Chiang, Michael F

2013-09-01

To evaluate quantitative and qualitative differences in documentation of the ophthalmic examination between paper and electronic health record (EHR) systems. Comparative case series. One hundred fifty consecutive pairs of matched paper and EHR notes, documented by 3 attending ophthalmologist providers. An academic ophthalmology department implemented an EHR system in 2006. Database queries were performed to identify cases in which the same problems were documented by the same provider on different dates, using paper versus EHR methods. This was done for 50 consecutive pairs of examinations in 3 different diseases: age-related macular degeneration (AMD), glaucoma, and pigmented choroidal lesions (PCLs). Quantitative measures were used to compare completeness of documenting the complete ophthalmologic examination, as well as disease-specific critical findings using paper versus an EHR system. Qualitative differences in paper versus EHR documentation were illustrated by selecting representative paired examples. (1) Documentation score, defined as the number of examination elements recorded for the slit-lamp examination, fundus examination, and complete ophthalmologic examination and for critical clinical findings for each disease. (2) Paired comparison of qualitative differences in paper versus EHR documentation. For all 3 diseases (AMD, glaucoma, PCL), the number of complete examination findings recorded was significantly lower with paper than the EHR system (P ≤ 0.004). Among the 3 individual examination sections (general, slit lamp, fundus) for the 3 diseases, 5 of the 9 possible combinations had significantly lower mean documentation scores with paper than EHR notes. For 2 of the 3 diseases, the number of critical clinical findings recorded was significantly lower using paper versus EHR notes (P ≤ 0.022). All (150/150) paper notes relied on graphical representations using annotated hand-drawn sketches, whereas no (0/150) EHR notes contained drawings. Instead, the EHR systems documented clinical findings using textual descriptions and interpretations. There were quantitative and qualitative differences in the nature of paper versus EHR documentation of ophthalmic findings in this study. The EHR notes included more complete documentation of examination elements using structured textual descriptions and interpretations, whereas paper notes used graphical representations of findings. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD.

PubMed

Hernández-Zimbrón, Luis Fernando; Zamora-Alvarado, Ruben; Ochoa-De la Paz, Lenin; Velez-Montoya, Raul; Zenteno, Edgar; Gulias-Cañizo, Rosario; Quiroz-Mercado, Hugo; Gonzalez-Salinas, Roberto

2018-01-01

Age-related macular degeneration (AMD) is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the "dry" and the "wet" form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1) advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2) this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

On the impact of different approaches to classify age-related macular degeneration: Results from the German AugUR study.

PubMed

Brandl, Caroline; Zimmermann, Martina E; Günther, Felix; Barth, Teresa; Olden, Matthias; Schelter, Sabine C; Kronenberg, Florian; Loss, Julika; Küchenhoff, Helmut; Helbig, Horst; Weber, Bernhard H F; Stark, Klaus J; Heid, Iris M

2018-06-06

While age-related macular degeneration (AMD) poses an important personal and public health burden, comparing epidemiological studies on AMD is hampered by differing approaches to classify AMD. In our AugUR study survey, recruiting residents from in/around Regensburg, Germany, aged 70+, we analyzed the AMD status derived from color fundus images applying two different classification systems. Based on 1,040 participants with gradable fundus images for at least one eye, we show that including individuals with only one gradable eye (n = 155) underestimates AMD prevalence and we provide a correction procedure. Bias-corrected and standardized to the Bavarian population, late AMD prevalence is 7.3% (95% confidence interval = [5.4; 9.4]). We find substantially different prevalence estimates for "early/intermediate AMD" depending on the classification system: 45.3% (95%-CI = [41.8; 48.7]) applying the Clinical Classification (early/intermediate AMD) or 17.1% (95%-CI = [14.6; 19.7]) applying the Three Continent AMD Consortium Severity Scale (mild/moderate/severe early AMD). We thus provide a first effort to grade AMD in a complete study with different classification systems, a first approach for bias-correction from individuals with only one gradable eye, and the first AMD prevalence estimates from a German elderly population. Our results underscore substantial differences for early/intermediate AMD prevalence estimates between classification systems and an urgent need for harmonization.

Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

PubMed

Mimura, Kensuke; Matsumoto, Hidetaka; Morimoto, Masahiro; Akiyama, Hideo

2018-01-01

To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended. © 2017 S. Karger AG, Basel.

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration

PubMed Central

Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W.; Jackson, Mary Lou

2018-01-01

Purpose Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. Methods We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Results Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). Conclusion In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL. PMID:29746512

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration.

PubMed

Roh, Miin; Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W; Jackson, Mary Lou

2018-01-01

Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL.

Treatment of combined acid mine drainage (AMD)--flotation circuit effluents from copper mine via Fenton's process.

PubMed

Mahiroglu, Ayse; Tarlan-Yel, Esra; Sevimli, Mehmet Faik

2009-07-30

The treatability of a copper mine wastewater, including heavy metals, AMD, as well as flotation chemicals, with Fenton process was investigated. Fenton process seems advantageous for this treatment, because of Fe(2+) content and low pH of AMD. First, optimum Fe(2+) condition under constant H(2)O(2) was determined, and initial Fe(2+) content of AMD was found sufficient (120 mg/L for removal of chemical oxygen demand (COD) of 6125 mg/L). In the second step, without any additional Fe(2+), optimum H(2)O(2) dosage was determined as 40 mg/L. Fe(2+)/H(2)O(2) molar ratio of 1.8 was enough to achieve the best treatment performance. In all trials, initial pH of AMD was 4.8 and pH adjustment was not performed. Utilization of existing pH and Fe(2+), low H(2)O(2) requirements, and up to 98% treatment performances in COD, turbidity, color, Cu(2+), Zn(2+) made the proposed treatment system promising. Since the reaction occurs stepwise, a two-step kinetic model was applied and calculated theoretical maximum removal rate was consistent to experimental one, which validates the applied model. For the optimum molar ratio (1.8), 140 mL/L sludge of high density (1.094 g/mL), high settling velocity (0.16 cm/s) with low specific resistance (3.15 x 10(8)m/kg) was obtained. High reaction rates and easily dewaterable sludge characteristics also made the proposed method advantageous.

Genetic factors of age-related macular degeneration

PubMed Central

Tuo, Jingsheng; Bojanowski, Christine M.; Chan, Chi-Chao

2007-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies. PMID:15094132

Polymorphisms in ARMS2/HTRA1 and Complement Genes and Age-Related Macular Degeneration in India: Findings from the INDEYE Study

PubMed Central

Sundaresan, Periasamy; Vashist, Praveen; Ravindran, Ravilla D.; Shanker, Ashwini; Nitsch, Dorothea; Nonyane, Bareng A. S.; Smeeth, Liam; Chakravarthy, Usha; Fletcher, Astrid E.

2012-01-01

Purpose. Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India. Methods. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1–3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center. Results. Of 3569 participants, 53.2% had no signs of AMD, 45.6% had features of early AMD, and 1.2% had late AMD. CFH (rs1061170), C2 (rs547154), or CFB (rs438999) was not associated with early or late AMD. In the ARMS2 locus, rs10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13–1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15–2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02–1.23; P = 0.02); rs10490923 was not associated with early or late AMD. Conclusions. Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India. PMID:23060141

Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

PubMed

Nashine, Sonali; Cohen, Pinchas; Chwa, Marilyn; Lu, Stephanie; Nesburn, Anthony B; Kuppermann, Baruch D; Kenney, M Cristina

2017-07-20

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD.

As(III) and As(V) removal from the aqueous phase via adsorption onto acid mine drainage sludge (AMDS) alginate beads and goethite alginate beads.

PubMed

Lee, Hongkyun; Kim, Dohyeong; Kim, Jongsik; Ji, Min-Kyu; Han, Young-Soo; Park, Young-Tae; Yun, Hyun-Shik; Choi, Jaeyoung

2015-07-15

Acid mine drainage sludge (AMDS) is a solid waste generated following the neutralization of acid mine drainage (AMD). This material entrapped in calcium alginate was investigated for the sorption of As(III) and As(V). Three different adsorbent materials were prepared: AMDS alginate beads (AABs), goethite alginate beads (GABs), and pure alginate beads. The effects of pH and the adsorption kinetics were investigated, and the adsorption isotherms were also evaluated. The optimum pH range using the AABs was determined to be within 2-10 for As(III) and 2-9 for As(V). Adsorption equilibrium data were evaluated using the Langmuir isotherm model, and the maximum adsorption capacity qmax was 18.25 and 4.97 mg g(-1) for As(III) on AAB and GAB, respectively, and 21.79 and 10.92 mg g(-1) for As(V) on AAB and GAB, respectively. The adsorption of As(III) and As(V) was observed to follow pseudo-second order kinetics. The As K-edge X-ray absorption near-edge structure (XANES) revealed that the adsorbed As(III) on the AABs was oxidized to As(V) via manganese oxide in the AMDS. Copyright © 2015 Elsevier B.V. All rights reserved.

A Novel Platelet-Activating Factor Receptor Antagonist Inhibits Choroidal Neovascularization and Subretinal Fibrosis

PubMed Central

Zhang, Han; Yang, Yang; Takeda, Atsunobu; Yoshimura, Takeru; Oshima, Yuji; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2013-01-01

Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration (AMD), the most common cause of blindness in developed countries. To date, the precise molecular and cellular mechanisms underlying CNV have not been elucidated. Platelet-activating factor (PAF) has been previously implicated in angiogenesis; however, the roles of PAF and its receptor (PAF-R) in CNV have not been addressed. The present study reveals several important findings concerning the relationship of the PAF-R signaling with CNV. PAF-R was detected in a mouse model of laser-induced CNV and was upregulated during CNV development. Experimental CNV was suppressed by administering WEB2086, a novel PAF-R antagonist. WEB2086-dependent suppression of CNV occurred via the inhibition of macrophage infiltration and the expression of proangiogenic (vascular endothelial growth factor) and proinflammatory molecules (monocyte chemotactic protein-1 and IL-6) in the retinal pigment epithelium–choroid complex. Additionally, WEB2086-induced PAF-R blockage suppresses experimentally induced subretinal fibrosis, which resembles the fibrotic subretinal scarring observed in neovascular AMD. As optimal treatment modalities for neovascular AMD would target the multiple mechanisms of AMD-associated vision loss, including neovascularization, inflammation and fibrosis, our results suggest PAF-R as an attractive molecular target in the treatment of AMD. PMID:23826375

[Potential of melatonin for prevention of age-related macular degeneration: experimental study].

PubMed

Stefanova, N A; Zhdankina, A A; Fursova, A Zh; Kolosova, N G

2013-01-01

Decline with age of the content of melatonin is considered as one of the leading mechanisms of aging and development of associated diseases, including age-related macular degeneration (AMD)--the disease, which becomes the most common cause of blindness and acuity of vision deterioration in elderly. The prospects of the use of melatonin in the prevention of AMD is being actively discussed, but as a rule on the basis of the results of the experiments on cells in retinal pigment epithelium (RPE). We showed previously that the senescence-accelerated OXYS rat is an adequate animal model of AMD, already used for identifying the relevant therapeutic targets. Here we have investigated the effect of Melatonin (Melaksen, 0,004 mg per kg--a dose equivalent to the recommended one for people) on the development of retinopathy similar to AMD in OXYS rats. Ophthalmoscopic examinations show that Melatonin supplementation decreased the incidence and severity of retinopathy and improved some (but not all) histological abnormalities associated with retinopathy. Thus, melatonin prevented the structural and functional changes in RPE cells, reduced the severity of microcirculatory disorders. Importantly, Melatonin prevented destruction of neurosensory cells, associative and gangliolar neurons in the retina. Taken together, our data suggest the therapeutic potential of Melatonin for treatment and prevention of AMD.

Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD

PubMed Central

Zamora-Alvarado, Ruben; Gulias-Cañizo, Rosario; Quiroz-Mercado, Hugo

2018-01-01

Age-related macular degeneration (AMD) is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the “dry” and the “wet” form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1) advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2) this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD. PMID:29484106

Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

PubMed

Klein, Ronald; Myers, Chelsea E; Cruickshanks, Karen J; Gangnon, Ronald E; Danforth, Lorraine G; Sivakumaran, Theru A; Iyengar, Sudha K; Tsai, Michael Y; Klein, Barbara E K

2014-04-01

IMPORTANCE Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. OBJECTIVE To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD. DESIGN, SETTING, AND PARTICIPANTS This longitudinal population-based cohort study involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to 4 follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010. EXPOSURES Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. Age-related macular degeneration was assessed from fundus photographs. MAIN OUTCOMES AND MEASURES Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-μm diameter) in the absence of late AMD. RESULTS The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio comparing fourth with first quartile, 2.18; P = .005), tumor necrosis factor-α receptor 2 (odds ratio, 1.78; P = .04), and interleukin-6 (odds ratio, 1.78; P = .03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with soluble vascular cell adhesion molecule-1 (odds ratio per SD on the logarithmic scale, 1.21; P = .04). CONCLUSIONS AND RELEVANCE We found modest evidence of relationships of serum high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and soluble vascular cell adhesion molecule-1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors. It is not known whether these associations represent a cause and effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.

Regulator Loss Functions and Hierarchical Modeling for Safety Decision Making.

PubMed

Hatfield, Laura A; Baugh, Christine M; Azzone, Vanessa; Normand, Sharon-Lise T

2017-07-01

Regulators must act to protect the public when evidence indicates safety problems with medical devices. This requires complex tradeoffs among risks and benefits, which conventional safety surveillance methods do not incorporate. To combine explicit regulator loss functions with statistical evidence on medical device safety signals to improve decision making. In the Hospital Cost and Utilization Project National Inpatient Sample, we select pediatric inpatient admissions and identify adverse medical device events (AMDEs). We fit hierarchical Bayesian models to the annual hospital-level AMDE rates, accounting for patient and hospital characteristics. These models produce expected AMDE rates (a safety target), against which we compare the observed rates in a test year to compute a safety signal. We specify a set of loss functions that quantify the costs and benefits of each action as a function of the safety signal. We integrate the loss functions over the posterior distribution of the safety signal to obtain the posterior (Bayes) risk; the preferred action has the smallest Bayes risk. Using simulation and an analysis of AMDE data, we compare our minimum-risk decisions to a conventional Z score approach for classifying safety signals. The 2 rules produced different actions for nearly half of hospitals (45%). In the simulation, decisions that minimize Bayes risk outperform Z score-based decisions, even when the loss functions or hierarchical models are misspecified. Our method is sensitive to the choice of loss functions; eliciting quantitative inputs to the loss functions from regulators is challenging. A decision-theoretic approach to acting on safety signals is potentially promising but requires careful specification of loss functions in consultation with subject matter experts.

ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.

PubMed

Wang, Jie; Zibetti, Cristina; Shang, Peng; Sripathi, Srinivasa R; Zhang, Pingwu; Cano, Marisol; Hoang, Thanh; Xia, Shuli; Ji, Hongkai; Merbs, Shannath L; Zack, Donald J; Handa, James T; Sinha, Debasish; Blackshaw, Seth; Qian, Jiang

2018-04-10

Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.

HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION.

PubMed

Schick, Tina; Ersoy, Lebriz; Lechanteur, Yara T E; Saksens, Nicole T M; Hoyng, Carel B; den Hollander, Anneke I; Kirchhof, Bernd; Fauser, Sascha

2016-04-01

To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information about current and past sunlight exposure, former occupation type, subdivided in indoor working and outdoor working, and iris color were obtained by standardized interviewer-assisted questionnaires. Associations between environmental factors adjusted for age, gender, and smoking and early and late AMD were performed by multivariate regression analysis. Current sunlight exposure showed no association with early AMD or late AMD, but past sunlight exposure (≥8 hours outside daily) was significantly associated with early AMD (odds ratio: 5.54, 95% confidence interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence interval 1.25-6.16, P = 0.01). Outside working was found to be associated with late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 × 10). No association was observed between iris color and early or late AMD. Sunlight exposure during working life is an important risk factor for AMD, whereas sunlight exposure after retirement seems to have less influence on the disease development. Therefore, preventive measures, for example, wearing sunglasses to minimize sunlight exposure, should start early to prevent development of AMD later in life.

Automatic age-related macular degeneration detection and staging

NASA Astrophysics Data System (ADS)

van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

2013-03-01

Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

Geochemical characteristics of dissolved rare earth elements in acid mine drainage from abandoned high-As coal mining area, southwestern China.

PubMed

Li, Xuexian; Wu, Pan

2017-09-01

Acid mine drainage (AMD) represents a major source of water pollution in the small watershed of Xingren coalfield in southwestern Guizhou Province. A detailed geochemical study was performed to investigate the origin, distribution, and migration of REEs by determining the concentrations of REEs and major solutes in AMD samples, concentrations of REEs in coal, bedrocks, and sediment samples, and modeling REEs aqueous species. The results highlighted that all water samples collected in the mining area are identified as low pH, high concentrations of Fe, Al, SO 4 2- and distinctive As and REEs. The spatial distributions of REEs showed a peak in where it is nearby the location of discharging of AMD, and then decrease significantly with distance away from the mining areas. Lots of labile REEs have an origin of coal and bedrocks, whereas the acid produced by the oxidation of pyrite is a prerequisite to cause the dissolution of coal and bedrocks, and then promoting REEs release in AMD. The North American Shale Composite (NASC)-normalized REE patterns of coal and bedrocks are enriched in light REEs (LREEs) and middle REEs (MREEs) relative to heavy REEs (HREEs). Contrary to these solid samples, AMD samples showed slightly enrichment of MREEs compared with LREEs and HREEs. This behavior implied that REEs probably fractionate during acid leaching, dissolution of bedrocks, and subsequent transport, so that the MREEs is primarily enriched in AMD samples. Calculation of REEs inorganic species for AMD demonstrated that sulfate complexes (Ln(SO 4 ) + and Ln(SO 4 ) 2 - ) predominate in these species, accounting for most of proportions for the total REEs species. The high concentrations of dissolved SO 4 2- and low pH play a decisive role in controlling the presence of REEs in AMD, as these conditions are necessary for formation of stable REEs-sulfate complexes in current study. The migration and transportation of REEs in AMD are more likely constrained by adsorption and co-precipitation of Fe-Al hydroxides/hydroxysulfate. In addition, the MREEs is preferentially captured by poorly crystalline Fe-Al hydroxides/hydroxysulfate, which favors that sediments also preserve NASC-normalized patterns with MREEs enrichment in the stream.

Contents, Followers, and Retweets of the Centers for Disease Control and Prevention's Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study.

PubMed

Fung, Isaac Chun-Hai; Jackson, Ashley M; Mullican, Lindsay A; Blankenship, Elizabeth B; Goff, Mary Elizabeth; Guinn, Amy J; Saroha, Nitin; Tse, Zion Tsz Ho

2018-04-02

The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle's entire contents and all followers. This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies' accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD's tweets referred to the Office's website and their current research; 17.6% (135/768) referred to their scientists' publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. This study confirms CDC health communicators' experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. ©Isaac Chun-Hai Fung, Ashley M Jackson, Lindsay A Mullican, Elizabeth B Blankenship, Mary Elizabeth Goff, Amy J Guinn, Nitin Saroha, Zion Tsz Ho Tse. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 02.04.2018.

Assessing quality of life in the treatment of patients with age-related macular degeneration: clinical research findings and recommendations for clinical practice

PubMed Central

Yuzawa, Mitsuko; Fujita, Kyoko; Tanaka, Erika; Wang, Edward C Y

2013-01-01

Background The importance of incorporating quality-of-life (QoL) assessments into medical practice is growing as health care practice shifts from a “disease-based” to a “patient-centered” model. The prevalence of age-related macular degeneration (AMD) is increasing in today’s aging population. The purpose of this paper is: (1) to discuss, by reviewing the current literature, the impact of AMD on patients’ QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2) to make a recommendation for incorporating QoL into clinical practice. Methods We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected. Results AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA). QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients’ valued activities, which are not captured by a single, numerical VA score. Conclusion The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease-specific instruments for measuring QoL, such as the NEI VFQ-25, have shown a significant correlation of QoL decrement with measures of disease severity, as well as significant QoL improvement with treatment. The NEI VFQ-25 and other validated instruments provide a wide-ranging assessment of vision-related functioning that is important to patients and complementary to VA measurement. We strongly recommend the incorporation of QoL assessment into routine clinical practice. PMID:23836961

Genetic association study of Age-Related Macular Degeneration in the Spanish population

PubMed Central

Brión, María; Sanchez-Salorio, Manuel; Cortón, Marta; de la Fuente, Maria; Pazos, Belen; Othman, Mohammad; Swaroop, Anand; Abecasis, Goncalo; Sobrino, Beatriz; Carracedo, Angel

2017-01-01

Purpose To investigate new genetic risk factors and replicate reported associations with advanced age related macular degeneration (AMD) in a prospective case - control study developed with a Spanish cohort. Methods Three hundred and fifty-three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age-matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlex™ genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3´UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. PMID:21106043

Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

PubMed

Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A; Klingeborn, Mikael

2013-12-13

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

FOUR-YEAR INCIDENCE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION: THE LOS ANGELES LATINO EYE STUDY

PubMed Central

Varma, Rohit; Foong, Athena W.P.; Lai, Mei-Ying; Choudhury, Farzana; Klein, Ronald; Azen, Stanley P.

2011-01-01

Purpose To estimate 4-year incidence and progression of early and advanced age-related macular degeneration (AMD). Design Population-based cohort study. Methods A comprehensive ophthalmologic examination including stereoscopic fundus photography was performed on adult Latinos at baseline and follow-up. Photographs were graded using a modified Wisconsin Age-Related Maculopathy Grading System. For estimations of incidence and progression of AMD, the Age Related Eye Disease Study Scale was used. Main outcome measures are incidence and progression of early AMD (drusen type, drusen size, and retinal pigmentary abnormalities) and advanced AMD (exudative AMD and geographic atrophy). Results 4,658/6100 (76%) completed the follow-up examination. The 4-year incidence of early AMD was 7.5% (95%CI:6.6,8.4) and advanced AMD was 0.2% (95%CI:0.1,0.4). Progression of any AMD occurred in 9.3% (95%CI:8.4,10.3) of at-risk participants. Incidence and progression increased with age. Incidence of early AMD in the second eye (10.8%) was higher than incidence in the first eye (6.9%). Baseline presence of soft indistinct large drusen≥250μm in diameter was more likely to predict the 4-year incidence of pigmentary abnormalities, geographic atrophy, and exudative AMD than smaller or hard or soft distinct drusen. Conclusions Age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites. While incident early AMD is more often unilateral, the risk of its development in the second is higher than in the first eye. Older persons and those with soft indistinct large drusen had a higher risk of developing advanced AMD compared to those who were younger and did not have soft indistinct large drusen. PMID:20399926

Harmonizing the Classification of Age-related Macular Degeneration in the Three Continent AMD Consortium

PubMed Central

Klein, Ronald; Meuer, Stacy M.; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Choudhury, Farzana; de Jong, Paulus T. V. M.; McKean-Cowdin, Roberta; Iyengar, Sudha K.; Gao, Xiaoyi; Lee, Kristine E.; Vingerling, Johannes R.; Mitchell, Paul; Klaver, Caroline C. W.; Wang, Jie Jin; Klein, Barbara E. K.

2014-01-01

Purpose To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), Los Angeles Latino Eye Study (LALES), and Rotterdam Study (RS). Methods AMD grading protocols, definitions of categories, and grading forms from each study were compared to determine whether there were systematic differences in AMD severity definitions and lesion categorization among the three grading centers. Each center graded the same set of 60 images using their respective systems to determine presence and severity of AMD lesions. A common five-step AMD severity scale and definitions of lesion measurement cutpoints and early and late AMD were developed from this exercise. Results Applying this severity scale changed the age-sex adjusted prevalence of early AMD from 18.7% to 20.3% in BDES, from 4.7% to 14.4% in BMES, from 14.1% to 15.8% in LALES, and from 7.5% to 17.1% in RS. Age-sex adjusted prevalences of late AMD remained unchanged. Comparison of each center’s grades of the 60 images converted to the consortium scale showed that exact agreement of AMD severity among centers varied from 61.0% to 81.4%, and one-step agreement varied from 84.7% to 98.3%. Conclusion Harmonization of AMD classification reduced categorical differences in phenotypic definitions across the studies, resulted in a new 5-step AMD severity scale, and enhanced similarity of AMD prevalence among four cohorts. Despite harmonization it may still be difficult to remove systematic differences in grading, if present. PMID:24467558

Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

PubMed Central

Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A.; Klingeborn, Mikael

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti–vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays. PMID:24335072

Genetic control of the alternative pathway of complement in humans and age-related macular degeneration

PubMed Central

Hecker, Laura A.; Edwards, Albert O.; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.; Issa, Peter Charbel; Scholl, Hendrik P.; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E.; Bailey, Kent R.; Oppermann, Martin

2010-01-01

Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues. PMID:19825847

CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy.

PubMed

Zhou, Zhike; Liu, Tingting; Sun, Xiaoyu; Mu, Xiaopeng; Zhu, Gang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

2017-03-30

It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration.

PubMed

Rowan, Sheldon; Jiang, Shuhong; Korem, Tal; Szymanski, Jedrzej; Chang, Min-Lee; Szelog, Jason; Cassalman, Christa; Dasuri, Kalavathi; McGuire, Christina; Nagai, Ryoji; Du, Xue-Liang; Brownlee, Michael; Rabbani, Naila; Thornalley, Paul J; Baleja, James D; Deik, Amy A; Pierce, Kerry A; Scott, Justin M; Clish, Clary B; Smith, Donald E; Weinberger, Adina; Avnit-Sagi, Tali; Lotan-Pompan, Maya; Segal, Eran; Taylor, Allen

2017-05-30

Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not. Critically, switching from the HG to the LG diet late in life arrested or reversed AMDf. LG diets limited the accumulation of advanced glycation end products, long-chain polyunsaturated lipids, and their peroxidation end-products and increased C3-carnitine in retina, plasma, or urine. Untargeted metabolomics revealed microbial cometabolites, particularly serotonin, as protective against AMDf. Gut microbiota were responsive to diet, and we identified microbiota in the Clostridiales order as being associated with AMDf and the HG diet, whereas protection from AMDf was associated with the Bacteroidales order and the LG diet. Network analysis revealed a nexus of metabolites and microbiota that appear to act within a gut-retina axis to protect against diet- and age-induced AMDf. The findings indicate a functional interaction between dietary carbohydrates, the metabolome, including microbial cometabolites, and AMDf. Our studies suggest a simple dietary intervention that may be useful in patients to arrest AMD.

Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis.

PubMed

Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan

2016-06-01

Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Contents, Followers, and Retweets of the Centers for Disease Control and Prevention’s Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study

PubMed Central

Blankenship, Elizabeth B; Goff, Mary Elizabeth; Guinn, Amy J; Saroha, Nitin; Tse, Zion Tsz Ho

2018-01-01

Background The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle’s entire contents and all followers. Objective This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Methods Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Results Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies’ accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD’s tweets referred to the Office’s website and their current research; 17.6% (135/768) referred to their scientists’ publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. Conclusions This study confirms CDC health communicators’ experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. PMID:29610112

Surface-water and groundwater interactions in an extensively mined watershed, upper Schuylkill River, Pennsylvania, USA

USGS Publications Warehouse

Cravotta, Charles A.; Goode, Daniel J.; Bartles, Michael D.; Risser, Dennis W.; Galeone, Daniel G.

2014-01-01

Streams crossing underground coal mines may lose flow, while abandoned mine drainage (AMD) restores flow downstream. During 2005-12, discharge from the Pine Knot Mine Tunnel, the largest AMD source in the upper Schuylkill River Basin, had near-neutral pH and elevated concentrations of iron, manganese, and sulfate. Discharge from the tunnel responded rapidly to recharge but exhibited a prolonged recession compared to nearby streams, consistent with rapid infiltration and slow release of groundwater from the mine. Downstream of the AMD, dissolved iron was attenuated by oxidation and precipitation while dissolved CO2 degassed and pH increased. During high-flow conditions, the AMD and downstream waters exhibited decreased pH, iron, and sulfate with increased acidity that were modeled by mixing net-alkaline AMD with recharge or runoff having low ionic strength and low pH. Attenuation of dissolved iron within the river was least effective during high-flow conditions because of decreased transport time coupled with inhibitory effects of low pH on oxidation kinetics. A numerical model of groundwater flow was calibrated using groundwater levels in the Pine Knot Mine and discharge data for the Pine Knot Mine Tunnel and the West Branch Schuylkill River during a snowmelt event in January 2012. Although the calibrated model indicated substantial recharge to the mine complex took place away from streams, simulation of rapid changes in mine pool level and tunnel discharge during a high flow event in May 2012 required a source of direct recharge to the Pine Knot Mine. Such recharge produced small changes in mine pool level and rapid changes in tunnel flow rate because of extensive unsaturated storage capacity and high transmissivity within the mine complex. Thus, elimination of stream leakage could have a small effect on the annual discharge from the tunnel, but a large effect on peak discharge and associated water quality in streams.

Physics of Lipofuscin Formation and Growth in Age Related Macular Degeneration

NASA Astrophysics Data System (ADS)

Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, Hans E.

2010-02-01

Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). With time, incompletely degraded membrane material builds up in the RPE in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease, and Parkinson disease. We will present the results of a study of the kinetics of lipofuscin growth in RPE cells using Kinetic Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. We compare our results to the number of lipofuscin granules in eyes with early age-related degeneration. )

Kinetics of Lipofuscin Formation in Aging Retinal Pigment Epithelium Cells

NASA Astrophysics Data System (ADS)

Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, Hans E.

2010-03-01

Lipofuscin is a deposit that is formed over time by aggregation and clustering of incompletely degraded membrane material in various types of cells. Lipofuscin is made of free-radical-damaged protein and fat and is known to be present in age- related macular dgeneration (AMD), Alzheimer disease, and Parkinson disease. AMD is the leading cause of blindness in adults. The degradation of retinal pigment epithelium cells (RPE) through accumulation of lipsofuscin is considered a significant pathogenic factor in the development of AMD. We will present the results of a study of the kinetics of lipofuscin growth in RPE cells using Kinetic Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. We compare our results with the number of lipofuscin granules in eyes with early age-related degeneration.

Initial Assessment and Modeling Framework Development for Automated Mobility Districts: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Yi; Young, Stanley E; Garikapati, Venu

Automated vehicles (AVs) are increasingly being discussed as the basis for on-demand mobility services, introducing a new paradigm in which a fleet of AVs displaces private automobiles for day-to-day travel in dense activity districts. This paper examines a concept to displace privately owned automobiles within a region containing dense activity generators (jobs, retail, entertainment, etc.), referred to as an automated mobility district (AMD). This paper reviews several such districts, including airports, college campuses, business parks, downtown urban cores, and military bases, with examples of previous attempts to meet the mobility needs apart from private automobiles, some with automated technology andmore » others with more traditional transit-based solutions. The issues and benefits of AMDs are framed within the perspective of intra-district, inter-district, and border issues, and the requirements for a modeling framework are identified to adequately reflect the breadth of mobility, energy, and emissions impact anticipated with AMDs« less

Development and Validation of a Risk Score for Age-Related Macular Degeneration: The STARS Questionnaire.

PubMed

Delcourt, Cécile; Souied, Eric; Sanchez, Alice; Bandello, Francesco

2017-12-01

To develop and validate a risk score for AMD based on a simple self-administered questionnaire. Risk factors having shown the most consistent associations with AMD were included in the STARS (Simplified Théa AMD Risk-Assessment Scale) questionnaire. Two studies were conducted, one in Italy (127 participating ophthalmologists) and one in France (80 participating ophthalmologists). During 1 week, participating ophthalmologists invited all their patients aged 55 years or older to fill in the STARS questionnaire. Based on fundus examination, early AMD was defined by the presence of soft drusen and/or pigmentary abnormalities and late AMD by the presence of geographic atrophy and/or neovascular AMD. The Italian and French samples consisted of 12,639 and 6897 patients, respectively. All 13 risk factors included in the STARS questionnaire showed significant associations with AMD in the Italian sample. The area under the receiving operating characteristic curve for the STARS risk score, derived from the multivariate logistic regression in the Italian sample, was 0.78 in the Italian sample and 0.72 in the French sample. In both samples, less than 10% of patients without AMD were classified at high risk, and less than 13% of late AMD cases were classified as low risk, with a more intermediate situation in early AMD cases. STARS is a new, simple self-assessed questionnaire showing good discrimination of risk for AMD in two large European samples. It might be used by ophthalmologists in routine clinical practice or as a self-assessment for risk of AMD in the general population.

HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

PubMed

Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

2007-05-02

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

Role of diet and food intake in age-related macular degeneration: a systematic review.

PubMed

Chapman, Naoko A; Jacobs, Robert J; Braakhuis, Andrea J

2018-06-21

A systematic literature review was conducted to evaluate the role of diet and food intake in age-related macular degeneration (AMD). Eighteen high-quality studies were identified. Adherence to a Mediterranean diet had decreased risk of AMD progression. An Oriental diet pattern had decreased association with AMD prevalence, whereas a Western diet pattern had increased association with AMD prevalence. High consumption of vegetables rich in carotenoids, and fatty fish containing omega-3 fatty acids was beneficial for those at risk of AMD. Vegetable oils and animal fats containing omega-6 fatty acids, and red/processed meat should be consumed minimally to reduce the risk of AMD progression. High glycaemic index diets and alcohol consumption of greater than two drinks a day had increased association with AMD. As the quality of diet and food intake had a vital role in AMD, the provision of appropriate nutritional advice to those at risk of AMD is recommended. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Functional Visual Improvement After Cataract Surgery in Eyes With Age-Related Macular Degeneration: Results of the Ophthalmic Surgical Outcomes Data Project.

PubMed

Stock, Michael V; Vollman, David E; Baze, Elizabeth F; Chomsky, Amy S; Daly, Mary K; Lawrence, Mary G

2015-04-01

To determine if cataract surgery on eyes with AMD confers as much functional visual improvement as surgery on eyes without retinal pathology. This is a retrospective analysis of 4924 cataract surgeries from the Veterans Healthcare Administration Ophthalmic Surgical Outcomes Data Project (OSOD). We included cases of eyes with AMD that had both preoperative and postoperative NEI-VFQ-25 questionnaires submitted and compared their outcomes with controls without retinal pathology. We excluded patients with other retinal pathologies (740 patients). The analyses compared changes in visual acuity and overall functional visual improvement and its subscales using t-tests, multivariate logistic regressions, and linear regression modeling. Preoperative and postoperative questionnaires were submitted by 58.3% of AMD and 63.8% of no retinal pathology cases (controls). Analysis of overall score showed that cataract surgery on eyes with AMD led to increased visual function (13.8 ± 2.4 NEI-VFQ units, P < 0.0001); however, increases were significantly less when compared with controls (-6.4 ± 2.9 NEI-VFQ units, P < 0.0001). Preoperative best-corrected visual acuity (preBCVA) in AMD was predictive of postoperative visual function (r = -0.38, P < 0.0001). In controls, postoperative visual function was only weakly associated with preBCVA (r = -0.075, P = 0.0002). Patients with AMD with vision of 20/40 or better had overall outcomes similar to controls (-2.2 ± 4.7 NEI-VFQ units, P = 0.37). Cataract surgery on eyes with AMD offers an increase in functional visual improvement; however, the amount of benefit is associated with the eye's preBCVA. For eyes with preBCVA of 20/40 or greater, the improvement is similar to that of patients without retinal pathology. However, if preBCVA is less than 20/40, the amount of improvement was shown to be significantly less and decreased with decreasing preBCVA.

GIS-based groundwater vulnerability modelling: A case study of the Witbank, Ermelo and Highveld Coalfields in South Africa

NASA Astrophysics Data System (ADS)

Sakala, E.; Fourie, F.; Gomo, M.; Coetzee, H.

2018-01-01

In the last 20 years, the popular mineral systems approach has been used successfully for the exploration of various mineral commodities at various scales owing to its scientific soundness, cost effectiveness and simplicity in mapping the critical processes required for the formation of deposits. In the present study this approach was modified for the assessment of groundwater vulnerability. In terms of the modified approach, water drives the pollution migration processes, with various analogies having been derived from the mineral systems approach. The modified approach is illustrated here by the discussion of a case study of acid mine drainage (AMD) pollution in the Witbank, Ermelo and Highveld coalfields of the Mpumalanga and KwaZulu-Natal Provinces in South Africa. Many AMD cases have been reported in these provinces in recent years and are a cause of concern for local municipalities, mining and environmental agencies. In the Witbank, Ermelo and Highveld coalfields, several areas have been mined out while mining has not yet started in others, hence the need to identify groundwater regions prone to AMD pollution in order to avoid further impacts on the groundwater resources. A knowledge-based fuzzy expert system was built using vulnerability factors (energy sources, ligands sources, pollutant sources, transportation pathways and traps) to generate a groundwater vulnerability model of the coalfields. Highly vulnerable areas were identified in Witbank coalfield and the eastern part of the Ermelo coalfield which are characterised by the presence of AMD sources, good subsurface transport coupled with poor AMD pollution trapping properties. The results from the analysis indicate significant correlations between model values and both groundwater sulphate concentrations as well as pH. This shows that the proposed approach can indeed be used as an alternative to traditional methods of groundwater vulnerability assessment. The methodology only considers the AMD pollution attenuation and migration at a regional scale and does not account for local-scale sources of pollution and attenuation. Further research to refine the approach may include the incorporation of groundwater flow direction, rock-pollution reaction time, and temporal datasets for the future prediction of groundwater vulnerability. The approach may be applied to other coalfields to assess its robustness to changing hydrogeological conditions.

Microbial Ecology and Evolution in the Acid Mine Drainage Model System.

PubMed

Huang, Li-Nan; Kuang, Jia-Liang; Shu, Wen-Sheng

2016-07-01

Acid mine drainage (AMD) is a unique ecological niche for acid- and toxic-metals-adapted microorganisms. These low-complexity systems offer a special opportunity for the ecological and evolutionary analyses of natural microbial assemblages. The last decade has witnessed an unprecedented interest in the study of AMD communities using 16S rRNA high-throughput sequencing and community genomic and postgenomic methodologies, significantly advancing our understanding of microbial diversity, community function, and evolution in acidic environments. This review describes new data on AMD microbial ecology and evolution, especially dynamics of microbial diversity, community functions, and population genomes, and further identifies gaps in our current knowledge that future research, with integrated applications of meta-omics technologies, will fill. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arsenic Scavenging by Al-Substituted Ferrihydrites in a Circumneutral pH River Impacted by the Acid Mine Drainage of Carnoulès, Gard, France

NASA Astrophysics Data System (ADS)

ADRA, A.; Morin, G.; ona-Nguema, G.; Maillot, F.; Casiot, C.; Bruneel, O.

2013-12-01

Ferrihydrite (Fh) is a nanocrystalline ferric oxyhydroxide involved in the retention of pollutants in natural systems and in water-treatment processes. The status and properties of major chemical impurities in natural Fh is however still scarcely documented. Here we investigated the structure and reactivity of aluminum-rich Fh from river-bed sediments collected in a circumneutral river (pH 6-7) impacted by an arsenic-rich acid mine drainage (AMD). Extended X-ray absorption fine structure (EXAFS) spectroscopy at the Fe K-edge shows that Fh is the predominant mineral phase forming after neutralization of the AMD, in association with minor amount of schwertmannite transported from the AMD. EXAFS analysis indicates that Al(III) substitutes for Fe(III) ions into the Fh structure in the natural sediment samples, with local aluminum concentration within the 20-37×7 mol%Al range, in agreement with bulk chemical compositions. Synthetic aluminous Fh analogues prepared in the present study are found to be less Al-substituted (14-18×4 mol%Al). Finally, EXAFS analysis at the arsenic K-edge indicates that As(V) form similar inner-sphere surface complexes on the natural and synthetic Al-substituted Fh studied. Our results provide direct evidences for the scavenging of arsenic by natural Al- Fh, with possible implications for other pollutants in natural or engineered systems.

Removal of heavy metals from acid mine drainage using chicken eggshells in column mode.

PubMed

Zhang, Ting; Tu, Zhihong; Lu, Guining; Duan, Xingchun; Yi, Xiaoyun; Guo, Chuling; Dang, Zhi

2017-03-01

Chicken eggshells (ES) as alkaline sorbent were immobilized in a fixed bed to remove typical heavy metals from acid mine drainage (AMD). The obtained breakthrough curves showed that the breakthrough time increased with increasing bed height, but decreased with increasing flow rate and increasing particle size. The Thomas model and bed depth service time model could accurately predict the bed dynamic behavior. At a bed height of 10 cm, a flow rate of 10 mL/min, and with ES particle sizes of 0.18-0.425 mm, for a multi-component heavy metal solution containing Cd 2+ , Pb 2+ and Cu 2+ , the ES capacities were found to be 1.57, 146.44 and 387.51 mg/g, respectively. The acidity of AMD effluent clearly decreased. The ES fixed-bed showed the highest removal efficiency for Pb with a better adsorption potential. Because of the high concentration in AMD and high removal efficiency in ES fixed-bed of iron ions, iron floccules (Fe 2 (OH) 2 CO 3 ) formed and obstructed the bed to develop the overall effectiveness. The removal process was dominated by precipitation under the alkaline reaction of ES, and the co-precipitation of heavy metals with iron ions. The findings of this work will aid in guiding and optimizing pilot-scale application of ES to AMD treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration*

PubMed Central

Ni, Jiaqian; Yuan, Xianglin; Gu, Jiayin; Yue, Xiuzhen; Gu, Xiaorong; Nagaraj, Ram H.; Crabb, John W.

2009-01-01

Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Nε-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorometry, respectively, and found higher mean levels of CML (∼54%) and pentosidine (∼64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch membrane, was elevated ∼86% in the AMD cohort, but autoantibody titers to CEP, CML, and pentosidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78, 79, and 88% accuracy, respectively, whereas CML in combination with pentosidine provided ∼89% accuracy, and CEP plus pentosidine provided ∼92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP adducts and with concurrent analyses of fructosyl-lysine to detect confounding factors. PMID:19435712

Autophagy regulating kinases as potential therapeutic targets for age-related macular degeneration.

PubMed

Kaarniranta, Kai; Kauppinen, Anu; Blasiak, Janusz; Salminen, Antero

2012-11-01

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly in the developed countries. The number of AMD patients will double during the next decades due to increasing number of aged people. Chronic oxidative stress, inflammation and accumulation of protein-rich deposits both in the retinal pigment epithelium lysosomes and under the retinal pigment epithelium herald the onset of AMD. The disease can be divided into dry and wet AMD forms. The dry form of the disease is more prevalent accounting for up to 90% of all cases. Continued intraocular injections are the current treatment strategy to prevent progression of wet AMD. It is a major challenge to develop new drugs that could prevent or at least ease the symptoms of the increasing population of AMD patients. Since AMD pathology is clearly associated with accumulated protein deposits, the autophagy clearance system might represent a potential future therapeutic target for AMD as is thoroughly discussed here.

Spatio-temporal variation of anthropogenic marine debris on Chilean beaches.

PubMed

Hidalgo-Ruz, Valeria; Honorato-Zimmer, Daniela; Gatta-Rosemary, Magdalena; Nuñez, Paloma; Hinojosa, Iván A; Thiel, Martin

2018-01-01

We examined the hypothesis that in an emerging economy such as Chile the abundances of Anthropogenic Marine Debris (AMD) on beaches are increasing over time. The citizen science program Científicos de la Basura ("Litter Scientists") conducted three national surveys (2008, 2012 and 2016) to determine AMD composition, abundance, spatial patterns and temporal trends. AMD was found on all beaches along the entire Chilean coast. Highest percentages of AMD in all surveys were plastics and cigarette butts, which can be attributed to local sources (i.e. beach users). The Antofagasta region in northern Chile had the highest abundance of AMD compared with all other zones. Higher abundances of AMD were found at the upper stations from almost all zones. No significant tendency of increasing or decreasing AMD densities was observed during the 8years covered by our study, which suggests that economic development alone cannot explain temporal trends in AMD densities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Do statins have a role in the prevention of age-related macular degeneration?

PubMed

Tsao, Sean W; Fong, Donald S

2013-04-01

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide for which preventative therapies are few. Evidence suggesting shared common risk factors and mirrored pathophysiology between cardiovascular disease and AMD led to the hypothesis that hydroxymethylglutaryl-CoA reductase inhibitors (statins) could be helpful in preventing AMD. For over a decade, observational studies have repeatedly investigated this hypothesis with conflicting conclusions. Although many reports conclude that statin use has no effect on the risk of AMD, no randomized controlled trial has yet been completed. Furthermore, relatively few studies factor characteristics of statin use into their analysis. A few studies have observed an incompletely explained protective effect against drusen, a funduscopic finding associated with AMD. Although there is insufficient evidence for a preventive effect of statins on dry AMD, there does seem to be stronger evidence against any effect on the development of exudative AMD. Overall, we find that there is insufficient evidence to conclude whether statin use is helpful in preventing AMD.

Clinical classification of age-related macular degeneration.

PubMed

Ferris, Frederick L; Wilkinson, C P; Bird, Alan; Chakravarthy, Usha; Chew, Emily; Csaky, Karl; Sadda, SriniVas R

2013-04-01

To develop a clinical classification system for age-related macular degeneration (AMD). Evidence-based investigation, using a modified Delphi process. Twenty-six AMD experts, 1 neuro-ophthalmologist, 2 committee chairmen, and 1 methodologist. Each committee member completed an online assessment of statements summarizing current AMD classification criteria, indicating agreement or disagreement with each statement on a 9-step scale. The group met, reviewed the survey results, discussed the important components of a clinical classification system, and defined new data analyses needed to refine a classification system. After the meeting, additional data analyses from large studies were provided to the committee to provide risk estimates related to the presence of various AMD lesions. Delphi review of the 9-item set of statements resulting from the meeting. Consensus was achieved in generating a basic clinical classification system based on fundus lesions assessed within 2 disc diameters of the fovea in persons older than 55 years. The committee agreed that a single term, age-related macular degeneration, should be used for the disease. Persons with no visible drusen or pigmentary abnormalities should be considered to have no signs of AMD. Persons with small drusen (<63 μm), also termed drupelets, should be considered to have normal aging changes with no clinically relevant increased risk of late AMD developing. Persons with medium drusen (≥ 63-<125 μm), but without pigmentary abnormalities thought to be related to AMD, should be considered to have early AMD. Persons with large drusen or with pigmentary abnormalities associated with at least medium drusen should be considered to have intermediate AMD. Persons with lesions associated with neovascular AMD or geographic atrophy should be considered to have late AMD. Five-year risks of progressing to late AMD are estimated to increase approximately 100 fold, ranging from a 0.5% 5-year risk for normal aging changes to a 50% risk for the highest intermediate AMD risk group. The proposed basic clinical classification scale seems to be of value in predicting the risk of late AMD. Incorporating consistent nomenclature into the practice patterns of all eye care providers may improve communication and patient care. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Downflow limestone beds for treatment of net-acidic, oxic, iron-laden drainage from a flooded Anthracite Mine, Pennsylvania, USA: 1. Field evaluation

USGS Publications Warehouse

Cravotta, C.A.; Ward, S.J.

2008-01-01

Passive-treatment systems that route acidic mine drainage (AMD) through crushed limestone and/or organic-rich substrates have been used to remove the acidity and metals from various AMD sources, with a wide range of effects. This study evaluates treatment of net-acidic, oxic, iron-laden AMD with limestone alone, and with organic-rich compost layered with the limestone. In the fall of 2003, a treatment system consisting of two parallel, 500-m2 downflow cells followed by a 400-m2 aerobic settling pond and wetland was installed to neutralize the AMD from the Bell Mine, a large source of AMD and baseflow to the Schuylkill River in the Southern Anthracite Coalfield, in east-central Pennsylvania. Each downflow cell consisted of a lower substrate layer of 1,090 metric tons (t) of dolomitic limestone (60 wt% CaCO3) and an upper layer of 300 t of calcitic limestone (95 wt% CaCO3); one of the downflow cells also included a 0.3 m thick layer of mushroom compost over the limestone. AMD with pH of 3.5-4.3, dissolved oxygen of 6.6-9.9 mg/L, iron of 1.9-5.4 mg/L, and aluminum of 0.8-1.9 mg/L flooded each cell to a depth 0.65 m above the treatment substrates, percolated through the substrates to underlying, perforated outflow pipes, and then flowed through the aerobic pond and wetland before discharging to the Schuylkill River. Data on the flow rates and chemistry of the effluent for the treatment system indicated substantial neutralization by the calcitic limestone but only marginal effects from the dolomitic limestone or compost. Because of its higher transmissivity, the treatment cell containing only limestone neutralized greater quantities of acidity than the cell containing compost and limestone. On average, the treatment system removed 62% of the influent acidity, 47% of the dissolved iron, 34% of the dissolved aluminum, and 8% of the dissolved manganese. Prior to treatment of the Bell Discharge, the Schuylkill River immediately below its confluence with the discharge had pH as low as 4.1 and supported few, if any, fish. However, within the first year of treatment, the pH was maintained at values of 5.0 or greater and native brook trout were documented immediately below the treatment system, though not above. ?? 2008 Springer-Verlag.

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

PubMed

Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L; Khawaja, Anthony P; Cougnard-Gregoire, Audrey; Merle, Bénédicte M J; Korb, Christina; Erke, Maja G; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T V M; Vingerling, Johannes R; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E; Foster, Paul J; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C W

2017-12-01

Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Meta-analysis of prevalence data. A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Prevalence of early and late AMD, BCVA, and number of AMD cases. Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti-vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease.

PubMed

Lindner, Moritz; Lambertus, Stanley; Mauschitz, Matthias M; Bax, Nathalie M; Kersten, Eveline; Lüning, Anna; Nadal, Jennifer; Schmitz-Valckenberg, Steffen; Schmid, Matthias; Holz, Frank G; Hoyng, Carel B; Fleckenstein, Monika

2017-02-01

To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbull's estimator. A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

The SDF-1/CXCR4 axis promotes recovery after spinal cord injury by mediating bone marrow-derived from mesenchymal stem cells

PubMed Central

Wang, Xiao; Zhang, Yong-Le; Zhang, Ya-Dong; Xue, Feng

2017-01-01

This study aims to explore the role of the SDF-1/CXCR4 axis in mediating BMSCs and SCI recovery. BMSCs were collected and SCI rat models were established. Wistar rats were assigned into the blank control, sham, SCI, SCI + BMSCs, SCI + BMSCs + SDF-1, SCI + BMSCs + AMD3100 (an inhibitor of SDF-1/CXCR4 axis) and SCI + BMSCs + SDF-1 + AMD3100 groups. Hind limb motor function was measured 7, 14, 21 and 28 days after operation. qRT-PCR, western blotting and ELISA was performed to determine the expressions of SDF-1, CXCR4, NGF, BDNF, GFAP and GAP-43, TNF-α, IL-1β, L-6 and IFN-γ. Hind limb motor function scores 7 days after the operation were reduced in the SCI rats of the blank control and sham groups. Hind limb function was found to be better in the SCI + BMSCs and SCI + BMSCs + SDF-1 groups than in the SCI, SCI + BMSCs + AMD3100 and SCI + BMSCs + SDF-1 + AMD3100 groups 14, 21 and 28 days after operation. Furthermore, the SCI group had lower SDF-1, CXCR4, NGF, BDNF and GAP-43 expressions but higher GFAP, TNF-α, IL-1β, IL-6 and IFN-γ than the blank control and sham groups 28 days after operation. While, the SCI + BMSCs, SCI + BMSCs + SDF-1 and SCI + BMSCs + SDF-1 + AMD3100 groups displayed opposite trends to the SCI and SCI + BMSCs + AMD3100 groups. In conclusion, SDF-1/CXCR4 axis promotes recovery after SCI by mediating BMSCs. PMID:28099928

Prevalence of neovascular age-related macular degeneration and geographic atrophy in Denmark.

PubMed

Sedeh, Farnam Barati; Scott, Daniel Andrew Richard; Subhi, Yousif; Sørensen, Torben Lykke

2017-11-01

In Denmark, age-related macular degeneration (AMD) is the most common cause of blindness. To better understand current and future challenges, we estimated and projected the annual number of patients with neovascular AMD and geographic atrophy in Denmark from 2016 to 2060. Detailed age- and gender-stratified prevalence estimates of neovascular AMD and geographic atrophy in a Scandinavian population were identified and applied to age- and gender-stratified population numbers provided by Statistics Denmark. Prevalence estimates were calculated for each year from 2016 to 2060. Future forecasts were provided by Statistics Denmark and based on calculations by the Danish Institute for Economic Modelling and Forecasting. We estimated that there are currently ~30,000 patients with neovascular AMD and ~21,000 patients with geographic atrophy in Denmark. The majority of these patients are persons aged ≥ 85 years. For neovascular AMD, the number of patients will grow to ~33,000 in 2020, ~58,000 in 2040 and ~72,000 in 2060. For geographic atrophy, the number of patients will grow to ~23,000 in 2020, ~41,000 in 2040, and ~50,000 in 2060. We expect a steady growth in the prevalence of neovascular AMD and geographic atrophy in Denmark due to an ageing population. These numbers emphasise the importance of disease prevention, careful planning of health service activities and continuing research. none. not relevant. Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Mitochondrial DNA Variants Mediate Energy Production and Expression Levels for CFH, C3 and EFEMP1 Genes: Implications for Age-Related Macular Degeneration

PubMed Central

Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Pavlis, Janelle M.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Hsu, Tiffany; Woo, Grace; Soe, Kyaw; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin

2013-01-01

Background Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD). Methodology/Principal Findings Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. Conclusion/Significance Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD. PMID:23365660

Age-related macular degeneration: economic burden and value-based medicine analysis.

PubMed

Brown, Melissa M; Brown, Gary C; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2005-06-01

It can be estimated that 17,100 new cases of neovascular (wet) AMD and 180,000 new cases of geographic-atrophy (dry) AMD occur in Canada annually. In addition to having a devastating effect on patients' lives, the condition causes significant adverse consequences for the economy. The deleterious effect of AMD on quality of life is markedly underestimated by ophthalmologists who treat patients with AMD, by non-ophthalmic physicians and by the public. In fact, patients with different degrees of severity of AMD have a perceived impairment of their quality of life that is 96% to 750% greater than the impairment estimated by treating ophthalmologists. Mild AMD causes a 17% decrease in the quality of life of the average patient, a decrease similar to that encountered with symptomatic human immunodeficiency virus infection or moderate cardiac angina. Moderate AMD produces a 40% decrease in quality of life, a decrease similar to that associated with permanent renal dialysis or severe cardiac angina. Very severe AMD causes a 63% decrement in quality of life, a decrease similar to that encountered with advanced prostatic cancer with uncontrollable pain or a severe stroke that leaves a person bedridden, incontinent and requiring constant nursing care. The adverse economic consequences of AMD include an annual $2.6 billion negative impact on Canada's gross domestic product. The return on investment is high for both current AMD therapies and research into new treatment modalities.

Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care.

PubMed

Neely, David C; Bray, Kevin J; Huisingh, Carrie E; Clark, Mark E; McGwin, Gerald; Owsley, Cynthia

2017-06-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment in older adults in the United States, yet little is known about whether AMD is appropriately diagnosed in primary eye care. To examine the prevalence of eyes with AMD in patients seen in primary eye care clinics who purportedly have normal macular health per their medical record and the association of AMD with patient and physician characteristics. In this cross-sectional study of primary eye care practices in Birmingham, Alabama, 644 persons 60 years or older with normal macular health per medical record based on their most recent dilated comprehensive eye examination by a primary eye care ophthalmologist or optometrist were enrolled from May 1, 2009, through December 31, 2011. Data analysis was performed from May 1, 2016, through December 20, 2016. Presence of AMD as defined by the Clinical Age-Related Maculopathy Staging system based on color fundus photography and a masked grader. Types of AMD-associated lesions were noted. Patient health and physician characteristics were collected. The sample consisted of 1288 eyes from 644 participants (231 [35.9%] male and 413 [64.1%] female; mean [SD] age, 69.4 [6.1] years; 611 white [94.9%]) seen by 31 primary eye care ophthalmologists or optometrists. A total of 968 eyes (75.2%) had no AMD, in agreement with their medical record; 320 (24.8%) had AMD despite no diagnosis of AMD in the medical record. Among eyes with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (13.4%) had hypopigmentation, 249 (77.8%) had small drusen, 250 (78.1%) had intermediate drusen, and 96 (30.0%) had large drusen. Undiagnosed AMD was associated with older patient age (odds ratio [OR], 1.06; 95% CI, 1.04-1.09; P < .001), male sex (age-adjusted OR, 1.39; 95% CI, 1.02-1.91; P = .04), and less than a high school education (age-adjusted OR, 2.40; 95% CI, 1.03-5.62; P = .04). Prevalence of undiagnosed AMD was not different for ophthalmologists and optometrists (age adjusted OR, 0.99; 95% CI, 0.71-1.36; P = .94). Approximately 25.0% of eyes deemed to be normal based on dilated eye examination by primary eye care physicians had macular characteristics that indicated AMD revealed by fundus photography and trained raters. A total of 30.0% of eyes with undiagnosed AMD had AMD with large drusen that would have been treatable with nutritional supplements had it been diagnosed. Improved AMD detection strategies may be needed in primary eye care as more effective treatment strategies for early AMD become available in the coming years.

Association of HTRA1 polymorphism and bilaterality in advanced age-related macular degeneration.

PubMed

Chen, Haoyu; Yang, Zhenglin; Gibbs, Daniel; Yang, Xian; Hau, Vincent; Zhao, Peiquan; Ma, Xiang; Zeng, Jiexi; Luo, Ling; Pearson, Erik; Constantine, Ryan; Kaminoh, Yuuki; Harmon, Jennifer; Tong, Zongzhong; Stratton, Charity A; Cameron, D Joshua; Tang, Shibo; Zhang, Kang

2008-02-01

Single nucleotide polymorphism (SNP), rs11200638, in the promoter of HTRA1 has recently been shown to increase the risk for AMD. In order to investigate the association of this HTRA1 polymorphism and the bilaterality of AMD, we genotyped rs11200638 in control, unilateral, and bilateral advanced AMD patients. The A allele for SNP rs11200638 in HTRA1, was significantly more prevalent in bilateral wet AMD and GA patients than in unilateral groups (p=.02 and p=.03, respectively). The homozygote odds ratios of bilateral wet AMD and GA are significantly greater than those seen in unilateral groups (twofold and threefold increase, respectively). This finding is consistent with the role of HTRA1 in AMD pathogenesis and will help aid in the clinical management and prognosis of AMD patients.

Identification of pathogenic genes and upstream regulators in age-related macular degeneration.

PubMed

Zhao, Bin; Wang, Mengya; Xu, Jing; Li, Min; Yu, Yuhui

2017-06-26

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AMD. To screen pathogenic genes of AMD, an integrated analysis was performed by using the microarray datasets in AMD derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AMD-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AMD. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs and TFs obtained by integrated analysis. From two GEO datasets obtained, we identified 1280 DEGs (730 up-regulated and 550 down-regulated genes) between AMD and normal control (NC). After KEGG analysis, steroid biosynthesis is a significantly enriched pathway for DEGs. The expression of 8 genes (TNC, GRP, TRAF6, ADAMTS5, GPX3, FAP, DHCR7 and FDFT1) was detected. Except for TNC and GPX3, the other 6 genes in qRT-PCR played the same pattern with that in our integrated analysis. The dysregulation of these eight genes may involve with the process of AMD. Two crucial transcription factors (c-rel and myogenin) were concluded to play a role in AMD. Especially, myogenin was associated with AMD by regulating TNC, GRP and FAP. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AMD.

Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration.

PubMed

Kaarniranta, Kai; Tokarz, Paulina; Koskela, Ali; Paterno, Jussi; Blasiak, Janusz

2017-04-01

Age-related macular degeneration (AMD) is an eye disease underlined by the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillares, but the exact mechanism of cell death in AMD is not completely clear. This mechanism is important for prevention of and therapeutic intervention in AMD, which is a hardly curable disease. Present reports suggest that both apoptosis and pyroptosis (cell death dependent on caspase-1) as well as necroptosis (regulated necrosis dependent on the proteins RIPK3 and MLKL, caspase-independent) can be involved in the AMD-related death of RPE cells. Autophagy, a cellular clearing system, plays an important role in AMD pathogenesis, and this role is closely associated with the activation of the NLRP3 inflammasome, a central event for advanced AMD. Autophagy can play a role in apoptosis, pyroptosis, and necroptosis, but its contribution to AMD-specific cell death is not completely clear. Autophagy can be involved in the regulation of proteins important for cellular antioxidative defense, including Nrf2, which can interact with p62/SQSTM, a protein essential for autophagy. As oxidative stress is implicated in AMD pathogenesis, autophagy can contribute to this disease by deregulation of cellular defense against the stress. However, these and other interactions do not explain the mechanisms of RPE cell death in AMD. In this review, we present basic mechanisms of autophagy and its involvement in AMD pathogenesis and try to show a regulatory role of autophagy in RPE cell death. This can result in considering the genes and proteins of autophagy as molecular targets in AMD prevention and therapy.

Pathogenic role and therapeutic potential of pleiotrophin in mouse models of ocular vascular disease.

PubMed

Wang, Weiwen; LeBlanc, Michelle E; Chen, Xiuping; Chen, Ping; Ji, Yanli; Brewer, Megan; Tian, Hong; Spring, Samantha R; Webster, Keith A; Li, Wei

2017-11-01

Angiogenic factors play an important role in the pathogenesis of diabetic retinopathy (DR), neovascular age-related macular degeneration (nAMD) and retinopathy of prematurity (ROP). Pleiotrophin, a well-known angiogenic factor, was recently reported to be upregulated in the vitreous fluid of patients with proliferative DR (PDR). However, its pathogenic role and therapeutic potential in ocular vascular diseases have not been defined in vivo. Here using corneal pocket assays, we demonstrated that pleiotrophin induced angiogenesis in vivo. To investigate the pathological role of pleiotrophin we used neutralizing antibody to block its function in multiple in vivo models of ocular vascular diseases. In a mouse model of DR, intravitreal injection of pleiotrophin-neutralizing antibody alleviated diabetic retinal vascular leakage. In a mouse model of oxygen-induced retinopathy (OIR), which is a surrogate model of ROP and PDR, we demonstrated that intravitreal injection of anti-pleiotrophin antibody prevented OIR-induced pathological retinal neovascularization and aberrant vessel tufts. Finally, pleiotrophin-neutralizing antibody ameliorated laser-induced choroidal neovascularization, a mouse model of nAMD, suggesting that pleiotrophin is involved in choroidal vascular disease. These findings suggest that pleiotrophin plays an important role in the pathogenesis of DR with retinal vascular leakage, ROP with retinal neovascularization and nAMD with choroidal neovascularization. The results also support pleiotrophin as a promising target for anti-angiogenic therapy.

LECTURES ON GAME THEORY, MARKOV CHAINS, AND RELATED TOPICS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, G L

1958-03-01

Notes on nine lectures delivered at Sandin Corporation in August 1957 are given. Part one contains the manuscript of a paper concerning a judging problem. Part two is concerned with finite Markov-chain theory amd discusses regular Markov chains, absorbing Markov chains, the classification of states, application to the Leontief input-output model, and semimartingales. Part three contains notes on game theory and covers matrix games, the effect of psychological attitudes on the outcomes of games, extensive games, amd matrix theory applied to mathematical economics. (auth)

The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

PubMed Central

Wang, Y; Wang, V M; Chan, C-C

2011-01-01

Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. PMID:21183941

The role of omega-3 and micronutrients in age-related macular degeneration.

PubMed

Querques, Giuseppe; Souied, Eric H

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States, Europe, and other developed countries. Although the pathogenesis of AMD remains unclear, current evidence suggests a multifactorial aetiology. Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We examine the relationship between dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explore the role of other micronutrients in AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration.

PubMed

Molins, Blanca; Romero-Vázquez, Sara; Fuentes-Prior, Pablo; Adan, Alfredo; Dick, Andrew D

2018-01-01

Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro . In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.

AMD-stability in the presence of first-order mean motion resonances

NASA Astrophysics Data System (ADS)

Petit, A. C.; Laskar, J.; Boué, G.

2017-11-01

The angular momentum deficit (AMD)-stability criterion allows to discriminate between a priori stable planetary systems and systems for which the stability is not granted and needs further investigations. AMD-stability is based on the conservation of the AMD in the averaged system at all orders of averaging. While the AMD criterion is rigorous, the conservation of the AMD is only granted in absence of mean-motion resonances (MMR). Here we extend the AMD-stability criterion to take into account mean-motion resonances, and more specifically the overlap of first-order MMR. If the MMR islands overlap, the system will experience generalized chaos leading to instability. The Hamiltonian of two massive planets on coplanar quasi-circular orbits can be reduced to an integrable one degree of freedom problem for period ratios close to a first-order MMR. We use the reduced Hamiltonian to derive a new overlap criterion for first-order MMR. This stability criterion unifies the previous criteria proposed in the literature and admits the criteria obtained for initially circular and eccentric orbits as limit cases. We then improve the definition of AMD-stability to take into account the short term chaos generated by MMR overlap. We analyze the outcome of this improved definition of AMD-stability on selected multi-planet systems from the Extrasolar Planets Encyclopædia.

Lack of association of CFD polymorphisms with advanced age-related macular degeneration.

PubMed

Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D; Nelson, Mark H; Tang, Luosheng; Zhang, Kang

2010-11-03

Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.

Do nutritional supplements have a role in age macular degeneration prevention?

PubMed

Pinazo-Durán, Maria D; Gómez-Ulla, Francisco; Arias, Luis; Araiz, Javier; Casaroli-Marano, Ricardo; Gallego-Pinazo, Roberto; García-Medina, Jose J; López-Gálvez, Maria Isabel; Manzanas, Lucía; Salas, Anna; Zapata, Miguel; Diaz-Llopis, Manuel; García-Layana, Alfredo

2014-01-01

Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids ( ω -3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω -3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of ω -3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω -3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

PubMed Central

Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Kautz, Leon; Roth, Marie-Paule; Dunaief, Joshua L.

2011-01-01

Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6−/− mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess. PMID:21703414

Education, socio-economic status and age-related macular degeneration in Asians: the Singapore Malay Eye Study.

PubMed

Cackett, P; Tay, W T; Aung, T; Wang, J J; Shankar, A; Saw, S M; Mitchell, P; Wong, T Y

2008-10-01

Low socio-economic status is increasingly being identified as a risk marker for chronic diseases, but few studies have investigated the link between socio-economic factors and age-related macular degeneration (AMD). The present study aimed to assess the association between socio-economic status and the prevalence of AMD. A population-based cross-sectional study of 3280 (78.7% response rate) Malay adults aged 40-80 years residing in 15 south-western districts of Singapore. AMD was graded from retinal photographs at a central reading centre using the modified Wisconsin AMD scale. Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system. Socio-economic status including education, housing type and income were determined from a detailed interview. Of the participants, 3265 had photographs of sufficient quality for grading of AMD. Early AMD was present in 168 (5.1%) and late AMD in 21 (0.6%). After adjusting for age, gender, smoking, hypertension, diabetes and body mass index, participants with lower educational levels were significantly more likely to have early AMD (multivariate OR 2.2, 95% CI 1.2 to 4.0). This association was stronger in persons who had never smoked (multivariate OR 3.6, 95% confidence CI 1.4 to 9.4). However, no association with housing type or income was seen. Low educational level is associated with a higher prevalence of early AMD signs in our Asian population, independent of age, cardiovascular risk factors and cigarette smoking.

Prevalence of age-related macular degeneration in rural southern China: the Yangxi Eye Study.

PubMed

Jin, Guangming; Ding, Xiaohu; Xiao, Wei; Xu, Xiao; Wang, Lanhua; Han, Xiaotong; Xiao, Ou; Liu, Ran; Wang, Wei; Yan, William; An, Lei; Zhao, Jialiang; He, Mingguang

2018-05-01

To describe the prevalence of age-related macular degeneration (AMD) among older adults in rural southern mainland China. Eligible persons aged 50 years or over were identified by geographically defined cluster sampling from Yangxi County, Guangdong Province, China. Participants underwent a standardised interview and comprehensive eye examinations from August to November in 2014. Digital retinal photographs were graded for AMD lesions using the Clinical Classification of Age-Related Macular Degeneration developed by the Beckman Initiative for Macular Research Classification Committee. Age-standardised prevalence of AMD and AMD lesions was calculated using the 2010 world population data and compared with those of other populations. Of 5825 subjects who participated (90.7% response rate), 4881 (83.8%) had fundus photographs gradable for AMD. Early, intermediate and late AMD were present in 2003 (41.0%), 879 (18.0%) and 42 (0.86%) participants. The age-standardised prevalence of early, intermediate and late AMD was 40.4% (95% CI 39.6% to 41.2%), 17.6% (95% CI 17.0% to 18.2%) and 0.79% (95% CI 0.65% to 0.95%), respectively. Total AMD was more prevalent in men than in women (62.8% vs 57.1%). AMD is an important public health concern for rural southern China, and the prevalence of AMD was higher in men than in women. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A 5-year multicenter prospective cohort study on the long-term visual prognosis and predictive factors for visual outcome in Japanese patients with age-related macular degeneration: the AMD2000 study.

PubMed

Akagi-Kurashige, Yumiko; Tsujikawa, Akitaka; Yuzawa, Mitsuko; Ishibashi, Tatsuro; Nakanishi, Hideo; Nakatani, Eiji; Teramukai, Satoshi; Fukushima, Masanori; Yoshimura, Nagahisa

2018-03-01

In this study (AMD2000), we aimed to determine the visual prognosis of Japanese patients with age-related macular degeneration (AMD). This was a multicenter prospective observational cohort study. In total, 460 patients with AMD were recruited from April 2006 to March 2009 from 18 clinical trial sites in Japan. They were followed up for 5 years, as they continued to receive medical treatment. Of the 409 study eyes followed up for at least 1 year, 243 eyes (59.4%) were treated with photodynamic therapy (PDT) using verteporfin, and 58 eyes (14.2%) were treated with intravitreal injections of antivascular endothelial growth factor agents as the initial treatment. The mean best-corrected visual acuities (BCVA) for typical AMD (tAMD; 0.688 ± 0.498) and polypoidal choroidal vasculopathy (PCV; 0.451 ± 0.395) were significantly less at 2 years (tAMD, 0.779 ± 0.632, P < 0.05; PCV, 0.534 ± 0.618, P < 0.05) and at 5 years (AMD, 0.873 ± 0.718, P < 0.05; PCV, 0.635 ± 0.668, P < 0.05) than at baseline. In eyes with tAMD, absence of blocked fluorescence was associated with 5-year maintenance of the baseline BCVA. Regarding PCV, the presence of polypoidal lesions and cystoid macular edema as well as the lesion size was associated with 5-year maintenance of the baseline BCVA. In some patients, the diagnosis changed: of the 192 eyes initially diagnosed with typical AMD, 19 were newly diagnosed with PCV during follow-up. Maintaining the baseline BCVA over the long term is difficult in Japanese eyes with wet AMD.

Nutritional Modulation of Age-Related Macular Degeneration

PubMed Central

Weikel, Karen A; Taylor, Allen

2012-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

Cost-effectiveness of anti-oxidant vitamins plus zinc treatment to prevent the progression of intermediate age-related macular degeneration. A Singapore perspective.

PubMed

Saxena, Nakul; George, Pradeep Paul; Heng, Bee Hoon; Lim, Tock Han; Yong, Shao Onn

2015-06-01

To determine if providing high dose anti-oxidant vitamins and zinc treatment age-related eye disease study (AREDS formulation) to patients with intermediate age-related macular degeneration (AMD) aged 40-79 years from Singapore is cost-effective in preventing progression to wet AMD. A hypothetical cohort of category 3 and 4 AMD patients from Singapore was followed for 5 calendar years to determine the number of patients who would progress to wet AMD given the following treatment scenarios: (a) AREDS formulation or placebo followed by ranibizumab (as needed) for wet AMD. (b) AREDS formulation or placebo followed by bevacizumab (monthly) for wet AMD. (c) AREDS formulation or placebo followed by aflibercept (VIEW I and II trial treatment regimen). Costs were estimated for the above scenarios from the providers' perspective, and cost-effectiveness was measured by cost per disability-adjusted life year (DALY) averted with a disability weight of 0.22 for wet AMD. The costs were discounted at an annual rate of 3%. Over 5400 patients could be prevented from progressing to wet AMD cumulatively if AREDS formulation were prescribed. AREDS formulation followed by ranibizumab was cost-effective compared to placebo-ranibizumab or placebo-aflibercept combinations (cost per DALY averted: SGD$23,662.3 and SGD$21,138.8, respectively). However, bevacizumab (monthly injections) alone was more cost-effective compared to AREDS formulation followed by bevacizumab. Prophylactic treatment with AREDS formulation for intermediate AMD patients followed by ranibizumab or for patients who progressed to wet AMD was found to be cost-effective. These findings have implications for intermediate AMD screening, treatment and healthcare planning in Singapore.

Prevention and treatment of age-related macular degeneration: an update for pharmacists.

PubMed

Marshall, Leisa L; Roach, J Michael

2013-11-01

Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements.

Compacted Sewage Sludge as a Barrier for Tailings: The Heavy Metal Speciation and Total Organic Carbon Content in the Compacted Sludge Specimen

PubMed Central

Zhang, Huyuan; Zhang, Qing; Yang, Bo; Wang, Jinfang

2014-01-01

Acid mine drainage (AMD) was the main environmental problem facing the mining industry. For AMD had high heavy metals content and low pH, the compacted sewage sludge might be a barrier for tailings whose oxidation and weathering produced AMD, with its own carbon source, microorganism reduction ability and impermeability. To study the heavy metals environmental risk, under the simulate AMD, the deionized water (DW), and the pH 2.1 sulfuric acid water (SA) seepage conditions, respectively, the changes of the chemical speciation of heavy metals Cd, Cu, Fe, Ni, Zn and total organic carbon (TOC) content in the compacted sewage sludge were assessed in the different periods. The results indicated according to the distribution of heavy metals, the potential mobility was for Cd: 6.08 under AMD, 7.48 under SA, ∞ under DW; for Cu: 0.08 under AMD, 0.17 under SA, 0.59 under DW; for Fe: 0.15 under AMD, 0.22 under SA, 0.22 under DW; for Ni: 2.60 under AMD, 1.69 under SA, 1.67 under DW; and for Zn: 0.15 under AMD, 0.23 under SA and 0.21 under DW at the second checking time. TOC content firstly decreased from 67.62±0% to 66.29±0.35%, then increased to 67.74±0.65% under the AMD seepage while TOC decreased to 63.30±0.53%, then to 61.33±0.37% under the DW seepage, decreased to 63.86±0.41%, then to 63.28±0.49% under SA seepage. That indicated under the AMD seepage, the suitable microorganisms communities in the compacted sewage sludge were activated. And the heavy metals environmental risk of compacted sewage sludge was lower with AMD condition than with other two. So the compacted sewage sludge as a barrier for tailings was feasible as the aspect of environmental risk assessment. PMID:24979755

Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

PubMed

Alster, Yair; Bressler, Neil M; Bressler, Susan B; Brimacombe, Judith A; Crompton, R Michael; Duh, Yi-Jing; Gabel, Veit-Peter; Heier, Jeffrey S; Ip, Michael S; Loewenstein, Anat; Packo, Kirk H; Stur, Michael; Toaff, Techiya

2005-10-01

To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. Prospective, comparative, concurrent, nonrandomized, multicenter study. Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the intermediate stage of AMD.

The effect of non-neovascular age-related macular degeneration on face recognition performance.

PubMed

Taylor, Deanna J; Smith, Nicholas D; Binns, Alison M; Crabb, David P

2018-04-01

There is a well-established research base surrounding face recognition in patients with age-related macular degeneration (AMD). However, much of this existing research does not differentiate between results obtained for 'wet' AMD and 'dry' AMD. Here, we test the hypothesis that face recognition performance is worse in patients with dry AMD compared with visually healthy peers. Patients (>60 years of age, logMAR binocular visual acuity 0.7 or better) with dry AMD of varying severity and visually healthy age-related peers (controls) completed a modified version of the Cambridge Face Memory Test (CFMT). Percentage of correctly identified faces was used as an outcome measure for performance for each participant. A 90% normative reference limit was generated from the distribution of CFMT scores recorded in the visually healthy controls. Scores for AMD participants were then specifically compared to this limit, and comparisons between average scores in the AMD severity groups were investigated. Thirty patients (median [interquartile range] age of 76 [70, 79] years) and 34 controls (median age of 70 [64, 75] years) were examined. Four, seventeen and nine patients were classified as having early, intermediate and late AMD (geographic atrophy) respectively. Five (17%) patients recorded a face recognition performance worse than the 90% limit (Fisher's exact test, p = 0.46) set by controls; four of these had geographic atrophy. Patients with geographic atrophy identified fewer faces on average (±SD) (61% ± 22%) than those with early and intermediate AMD (75 ± 11%) and controls (74% ± 11%). People with dry AMD may not suffer from problems with face recognition until the disease is in its later stages; those with late AMD (geographic atrophy) are likely to have difficulty recognising faces. The results from this study should influence the management and expectations of patients with dry AMD in both community practice and hospital clinics.

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.

PubMed

Meyers, Kristin J; Liu, Zhe; Millen, Amy E; Iyengar, Sudha K; Blodi, Barbara A; Johnson, Elizabeth; Snodderly, D Max; Klein, Michael L; Gehrs, Karen M; Tinker, Lesley; Sarto, Gloria E; Robinson, Jennifer; Wallace, Robert B; Mares, Julie A

2015-11-01

Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated. Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively. AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD. The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Microbial communities, processes and functions in acid mine drainage ecosystems.

PubMed

Chen, Lin-xing; Huang, Li-nan; Méndez-García, Celia; Kuang, Jia-liang; Hua, Zheng-shuang; Liu, Jun; Shu, Wen-sheng

2016-04-01

Acid mine drainage (AMD) is generated from the oxidative dissolution of metal sulfides when water and oxygen are available largely due to human mining activities. This process can be accelerated by indigenous microorganisms. In the last several decades, culture-dependent researches have uncovered and validated the roles of AMD microorganisms in metal sulfides oxidation and acid generation processes, and culture-independent studies have largely revealed the diversity and metabolic potentials and activities of AMD communities, leading towards a full understanding of the microbial diversity, functions and interactions in AMD ecosystems. This review describes the diversity of microorganisms and their functions in AMD ecosystems, and discusses their biotechnological applications in biomining and AMD bioremediation according to their capabilities. Copyright © 2016 Elsevier Ltd. All rights reserved.

How Does the Macula Protect Itself from Oxidative Stress?

PubMed Central

Handa, James T.

2012-01-01

Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD. PMID:22503691

NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration.

PubMed

Wang, Yujuan; Hanus, Jakub W; Abu-Asab, Mones S; Shen, Defen; Ogilvy, Alexander; Ou, Jingxing; Chu, Xi K; Shi, Guangpu; Li, Wei; Wang, Shusheng; Chan, Chi-Chao

2016-01-08

Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis.

How does the macula protect itself from oxidative stress?

PubMed

Handa, James T

2012-08-01

Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reaction mechanisms and multifragmentation processes in 64Zn+58Ni at 35A-79A MeV

NASA Astrophysics Data System (ADS)

Wada, R.; Hagel, K.; Cibor, J.; Gonin, M.; Keutgen, Th.; Murray, M.; Natowitz, J. B.; Ono, A.; Steckmeyer, J. C.; Kerambrum, A.; Angélique, J. C.; Auger, A.; Bizard, G.; Brou, R.; Cabot, C.; Crema, E.; Cussol, D.; Durand, D.; El Masri, Y.; Eudes, P.; He, Z. Y.; Jeong, S. C.; Lebrun, C.; Patry, J. P.; Péghaire, A.; Peter, J.; Régimbart, R.; Rosato, E.; Saint-Laurent, F.; Tamain, B.; Vient, E.

2000-09-01

Reaction mechanisms and multifragmentation processes have been studied for 64Zn+58Ni collisions at intermediate energies with the help of antisymmetrized molecular dynamics (AMD-V) model calculations. Experimental energy spectra, angular distributions, charge distributions, and isotope distributions, classified by their associated charged particle multiplicities, are compared with the results of the AMD-V calculations. In general the experimental results are reasonably well reproduced by the calculations. The multifragmentation observed experimentally at all incident energies is also reproduced by the AMD-V calculations. A detailed study of AMD-V events reveals that, in nucleon transport, the reaction shows some transparency, whereas in energy transport the reaction is much less transparent at all incident energies studied here. The transparency in the nucleon transport indicates that, even for central collisions, about 75% of the projectile nucleons appear in the forward direction. In energy transport about 80% of the initial kinetic energy of the projectile in the center- of-mass frame is dissipated. The detailed study of AMD-V events also elucidates the dynamics of the multifragmentation process. The study suggests that, at 35A MeV, the semitransparency and thermal expansion are the dominant mechanisms for the multifragmentation process, whereas at 49A MeV and higher incident energies a nuclear compression occurs at an early stage of the reaction and plays an important role in the multifragmentation process in addition to that of the thermal expansion and the semitransparency.

Sensitivity of the mayfly Adenophlebia auriculata (Ephemeroptera: Leptophlebiidae) to MgSO4 and Na2SO4

NASA Astrophysics Data System (ADS)

Vellemu, E. C.; Mensah, P. K.; Griffin, N. J.; Odume, O. N.

2017-08-01

Acid mine drainage (AMD) continues to deteriorate water quality in freshwater ecosystems. Sulphates, a major salt component in AMD, can exacerbate AMD effects in freshwater because salts are toxic to aquatic life in high concentrations. Sulphates are predominant in South African AMD impacted freshwater ecosystems. In this study, the sensitivity of nymphs of the mayfly Adenophlebia auriculata (Ephemeroptera: Leptophlebiidae) was investigated by exposing the organisms to magnesium sulphate (MgSO4) and sodium sulphate (Na2SO4) as models of mining salinisation in short-term (96 h) and long-term (240 h) in static system tests. Short-term and long-term lethal concentrations of each salt were estimated using regression analyses. The results indicated that A. auriculata was more sensitive to MgSO4 (LC50 = 3.81 g/L) than Na2SO4 (LC50 = 8.78 g/L) after short-term exposures. However, this species became sensitive to Na2SO4 (LC10 = 0.19 g/L) but tolerant to MgSO4 (LC10 = 0.35 g/L) after long-term exposures. These results suggest that the 0.25 g/L sulphate compliance limit for South Africa is inadequate to protect A. auriculata from Na2SO4 toxicity in the long-term, yet it overprotects this species from MgSO4 exposures in the short-term. The findings of this study are an important major step in understanding the ecological effects of AMD to aquatic life.

Radium and barium removal through blending hydraulic fracturing fluids with acid mine drainage.

PubMed

Kondash, Andrew J; Warner, Nathaniel R; Lahav, Ori; Vengosh, Avner

2014-01-21

Wastewaters generated during hydraulic fracturing of the Marcellus Shale typically contain high concentrations of salts, naturally occurring radioactive material (NORM), and metals, such as barium, that pose environmental and public health risks upon inadequate treatment and disposal. In addition, fresh water scarcity in dry regions or during periods of drought could limit shale gas development. This paper explores the possibility of using alternative water sources and their impact on NORM levels through blending acid mine drainage (AMD) effluent with recycled hydraulic fracturing flowback fluids (HFFFs). We conducted a series of laboratory experiments in which the chemistry and NORM of different mix proportions of AMD and HFFF were examined after reacting for 48 h. The experimental data combined with geochemical modeling and X-ray diffraction analysis suggest that several ions, including sulfate, iron, barium, strontium, and a large portion of radium (60-100%), precipitated into newly formed solids composed mainly of Sr barite within the first ∼ 10 h of mixing. The results imply that blending AMD and HFFF could be an effective management practice for both remediation of the high NORM in the Marcellus HFFF wastewater and beneficial utilization of AMD that is currently contaminating waterways in northeastern U.S.A.

Generation of acid mine drainage around the Karaerik copper mine (Espiye, Giresun, NE Turkey): implications from the bacterial population in the Acısu effluent.

PubMed

Sağlam, Emine Selva; Akçay, Miğraç; Çolak, Dilşat Nigar; İnan Bektaş, Kadriye; Beldüz, Ali Osman

2016-09-01

The Karaerik Cu mine is a worked-out deposit with large volumes of tailings and slags which were left around the mine site without any protection. Natural feeding of these material and run-off water from the mineralised zones into the Acısu effluent causes a serious environmental degradation and creation of acid mine drainage (AMD) along its entire length. This research aims at modelling the formation of AMD with a specific attempt on the characterisation of the bacterial population in association with AMD and their role on its occurrence. Based on 16SrRNA analyses of the clones obtained from a composite water sample, the bacterial community was determined to consist of Acidithiobacillus ferrivorans, Ferrovum myxofaciens, Leptospirillum ferrooxidans and Acidithiobacillus ferrooxidans as iron-oxidising bacteria, Acidocella facilis, Acidocella aluminiidurans, Acidiphilium cryptum and Acidiphilium multivorum as iron-reducing bacteria, and Acidithiobacillus ferrivorans, Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans and Acidiphilium cryptum as sulphur-oxidising bacteria. This association of bacteria with varying roles was interpreted as evidence of a concomitant occurrence of sulphur and iron cycles during the generation of AMD along the Acısu effluent draining the Karaerik mine.

The effect of retinal pigment epithelial cell patch size on growth factor expression

DOE PAGES

Vargis, Elizabeth A.; Peterson, Cristen B.; Morrell-Falvey, Jennifer L.; ...

2014-01-30

The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function thatmore » occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. As a result, up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.« less

Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration

PubMed Central

Sripathi, Srinivas R.; He, Weilue; Prigge, Cameron L.; Sylvester, O’Donnell; Um, Ji-Yeon; Powell, Folami L.; Neksumi, Musa; Bernstein, Paul S.; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R.; Jahng, Wan Jin

2017-01-01

The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration. PMID:28580316

Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration.

PubMed

Sripathi, Srinivas R; He, Weilue; Prigge, Cameron L; Sylvester, O'Donnell; Um, Ji-Yeon; Powell, Folami L; Neksumi, Musa; Bernstein, Paul S; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R; Jahng, Wan Jin

2017-02-01

The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration.

Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.

PubMed

Bressler, Neil M; Bressler, Susan B; Congdon, Nathan G; Ferris, Frederick L; Friedman, David S; Klein, Ronald; Lindblad, Anne S; Milton, Roy C; Seddon, Johanna M

2003-11-01

To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

NASA Astrophysics Data System (ADS)

Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

2016-05-01

The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

Novel grid combined with peripheral distortion correction for ultra-widefield image grading of age-related macular degeneration

PubMed Central

Mach, Steven; Garas, Shady; Kim, Ivana K; Vavvas, Demetrios G; Miller, Joan W; Husain, Deeba; Miller, John B

2017-01-01

Purpose Eyes with age-related macular degeneration (AMD) often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF) imaging. Methods This is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images. Results Peripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD. Conclusion We present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation for the exploration of peripheral retinal pathology associated with AMD. PMID:29184386

Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

PubMed

Toschi-Dias, Edgar; Trombetta, Ivani C; da Silva, Valdo José Dias; Maki-Nunes, Cristiane; Alves, Maria Janieire N N; Angelo, Luciana F; Cepeda, Felipe X; Martinez, Daniel G; Negrão, Carlos Eduardo; Rondon, Maria Urbana P B

2013-03-01

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

Reporting quality of randomised controlled trial abstracts on age-related macular degeneration health care: a cross-sectional quantification of the adherence to CONSORT abstract reporting recommendations.

PubMed

Baulig, Christine; Krummenauer, Frank; Geis, Berit; Tulka, Sabrina; Knippschild, Stephanie

2018-05-22

To assess the reporting quality of randomised controlled trial (RCT) abstracts on age-related macular degeneration (AMD) healthcare, to evaluate the adherence to the Consolidated Standards of Reporting Trials (CONSORT) statement's recommendations on minimum abstract information and to identify journal characteristics associated with abstract reporting quality. Cross-sectional evaluation of RCT abstracts on AMD healthcare. A PubMed search was implemented to identify RCT abstracts on AMD healthcare published in the English language between January 2004 and December 2013. Data extraction was performed by two parallel readers independently by means of a documentation format in accordance with the 16 items of the CONSORT checklist for abstracts. The total number of criteria fulfilled by an abstract was derived as primary endpoint of the investigation; incidence rate ratios (IRRs) with unadjusted 95% CI were estimated by means of multiple Poisson regression to identify journal and article characteristics (publication year, multicentre design, structured abstract recommendations, effective sample size, effective abstract word counts and journal impact factor) possibly associated with the total number of fulfilled items. 136 of 673 identified abstracts (published in 36 different journals) fulfilled all eligibility criteria. The median number of fulfilled items was 7 (95% CI 7 to 8). No abstract reported all 16 recommended items; the maximum total number was 14, the minimum 3 of 16 items. Multivariate analysis only demonstrated the abstracts' word counts as being significantly associated with a better reporting of abstracts (Poisson regression-based IRR 1.002, 95% CI 1.001 to 1.003). Reporting quality of RCT abstracts on AMD investigations showed a considerable potential for improvement to meet the CONSORT abstract reporting recommendations. Furthermore, word counts of abstracts were identified as significantly associated with the overall abstract reporting quality. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

PubMed

Shroyer, N F; Lewis, R A; Yatsenko, A N; Wensel, T G; Lupski, J R

2001-11-01

Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations may be predisposed to develop the multifactorial disorder age-related macular degeneration (AMD). We hypothesized that some carriers of STGD alleles have an increased risk to develop AMD. We tested this hypothesis in a cohort of families that manifest both STGD and AMD. With a direct-sequencing mutation detection strategy, we found that AMD-affected relatives of STGD patients are more likely to be carriers of pathogenic STGD alleles than predicted based on chance alone. We further investigated the role of AMD-associated ABCR mutations by testing for expression and ATP-binding defects in an in vitro biochemical assay. We found that mutations associated with AMD have a range of assayable defects ranging from no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations reported in patients with AMD, 16 (76%) show abnormalities in protein expression, ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients are predisposed to develop AMD.

Arsenic scavenging by aluminum-substituted ferrihydrites in a circumneutral pH river impacted by acid mine drainage.

PubMed

Adra, Areej; Morin, Guillaume; Ona-Nguema, Georges; Menguy, Nicolas; Maillot, Fabien; Casiot, Corinne; Bruneel, Odile; Lebrun, Sophie; Juillot, Farid; Brest, Jessica

2013-11-19

Ferrihydrite (Fh) is a nanocrystalline ferric oxyhydroxide involved in the retention of pollutants in natural systems and in water-treatment processes. The status and properties of major chemical impurities in natural Fh is however still scarcely documented. Here we investigated the structure of aluminum-rich Fh, and their role in arsenic scavenging in river-bed sediments from a circumneutral river (pH 6-7) impacted by an arsenic-rich acid mine drainage (AMD). Extended X-ray absorption fine structure (EXAFS) spectroscopy at the Fe K-edge shows that Fh is the predominant mineral phase forming after neutralization of the AMD, in association with minor amount of schwertmannite transported from the AMD. TEM-EDXS elemental mapping and SEM-EDXS analyses combined with EXAFS analysis indicates that Al(3+) substitutes for Fe(3+) ions into the Fh structure in the natural sediment samples, with local aluminum concentration within the 25-30 ± 10 mol %Al range. Synthetic aluminous Fh prepared in the present study are found to be less Al-substituted (14-20 ± 5 mol %Al). Finally, EXAFS analysis at the arsenic K-edge indicates that As(V) form similar inner-sphere surface complexes on the natural and synthetic Al-substituted Fh studied. Our results provide direct evidence for the scavenging of arsenic by natural Al-Fh, which emphasize the possible implication of such material for scavenging pollutants in natural or engineered systems.

Crystal structure and superconductivity in atomic hydrogen: Deformation between I41/amd and Fddd

NASA Astrophysics Data System (ADS)

Ishikawa, T.; Nagara, H.; Oda, T.; Suzuki, N.; Shimizu, K.

2017-10-01

We investigated crystal structures of solid metallic hydrogen using the potential energy surface trekking for structure search. We applied this technique to a tetragonal I41/amd structure at pressures of 500 and 600 GPa and obtained the transformation into multiple orthorhombic Fddd structures, which are formed by distortions in the ab plane of I41/amd. The potential barriers are easily surmounted by few trekking steps, which indicates that in solid metallic hydrogen crystal structure is softened with respect to the distortion and is easily fluctuated among the I41/amd and Fddd structures. Calculated superconducting critical temperatures show 269 K for I41/amd and 263 K for Fddd at 500 GPa. The structures are softened and the electron-phonon coupling are enhanced with pressurization to 600 GPa. As the results, the superconducting critical temperature is increased to 281 K for I41/amd, whereas it is decreased to 252 K for Fddd owing to its larger phonon softening than that of I41/amd.

Ranibizumab for the treatment of neovascular AMD.

PubMed

Kaiser, P K; Do, D V

2007-03-01

Age-related macular degeneration (AMD) is the leading cause of adult blindness among individuals aged 50 and older in the Western world, with the neovascular form of AMD responsible for the most severe and rapid visual loss. Although monotherapy with currently available treatments can slow the rate of loss of vision in eyes with neovascular AMD, they do not significantly improve vision. Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the pathogenesis of neovascular AMD, and ranibizumab is a promising new treatment that targets all VEGF-A isoforms and their biologically active degradation products. Clinical trials have reported that ranibizumab treatment resulted in greater proportions of patients achieving a < 15 letter loss of visual acuity and improved vision at 12 and 24 months than control groups. The incidence of serious ocular and systemic adverse events was low in all ranibizumab trials to date. Currently, ranibizumab is the only treatment for neovascular AMD to demonstrate significant improvement in vision for many patients and represents a major advance in treating neovascular AMD.

Nutrition and age-related macular degeneration: research evidence in practice.

PubMed

Downie, Laura Elizabeth; Keller, Peter Richard

2014-08-01

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in developed countries. In the absence of effective treatments to slow AMD progression, it is predicted that the prevalence of AMD will double over the next 20 years. One area of significant interest is the potential role that nutrition may play in preventing and/or delaying the progression of AMD. Specifically, is there any benefit in oral antioxidant and/or mineral supplementation? This review critically evaluates the currently available evidence relating to nutrition and AMD, with particular reference to the key findings of two large National Eye Institute-sponsored clinical studies, namely, the Age-Related Eye Disease Study (AREDS) and AREDS2. Topical controversies relating to nutrition and AMD are considered and analyzed in the context of the published literature to guide practitioners through assessing the merit, or otherwise, of common claims. This article provides a foundation for clinicians to provide informed advice to AMD patients based on available research evidence.

Analysis OpenMP performance of AMD and Intel architecture for breaking waves simulation using MPS

NASA Astrophysics Data System (ADS)

Alamsyah, M. N. A.; Utomo, A.; Gunawan, P. H.

2018-03-01

Simulation of breaking waves by using Navier-Stokes equation via moving particle semi-implicit method (MPS) over close domain is given. The results show the parallel computing on multicore architecture using OpenMP platform can reduce the computational time almost half of the serial time. Here, the comparison using two computer architectures (AMD and Intel) are performed. The results using Intel architecture is shown better than AMD architecture in CPU time. However, in efficiency, the computer with AMD architecture gives slightly higher than the Intel. For the simulation by 1512 number of particles, the CPU time using Intel and AMD are 12662.47 and 28282.30 respectively. Moreover, the efficiency using similar number of particles, AMD obtains 50.09 % and Intel up to 49.42 %.

Energy Assessment of Automated Mobility Districts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yuche

Automated vehicles (AVs) are increasingly being discussed as the basis for on-demand mobility services, introducing a new paradigm in which a fleet of AVs displace private automobiles for day-to-day travel in dense activity districts. This project examines such a concept to displace privately owned automobiles within a region containing dense activity generators (jobs, retail, entertainment, etc.), referred to as an automated mobility district (AMDs). The project reviews several such districts including airport, college campuses, business parks, downtown urban cores, and military bases, with examples of previous attempts to meet the mobility needs apart from private automobiles, some with automated technologymore » and others with more traditional transit based solutions. The issues and benefits of AMDs are framed within the perspective of intra-district, inter-district, and border issues, and the requirements for a modeling framework are identified to adequately reflect the breadth of mobility, energy, and emissions impact anticipated with AMDs.« less

Brueckner-AMD Study of Light Nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Kiyoshi; Yamamoto, Yuhei; Togashi, Tomoaki

2011-06-28

We applied the Brueckner theory to the Antisymmetrized Molecular Dynamics (AMD) and examined the reliability of the AMD calculations based on realistic nuclear interactions. In this method, the Bethe-Goldstone equation in the Brueckner theory is solved for every nucleon pair described by wave packets of AMD, and the G-matrix is calculated with single-particle orbits in AMD self-consistently. We apply this framework to not only {alpha}-nuclei but also N{ne}Z nuclei with A{approx}10. It is confirmed that these results present the description of reasonable cluster structures and energy-level schemes comparable with the experimental ones in light nuclei.

Natural history of drusenoid pigment epithelial detachment in age-related macular degeneration: Age-Related Eye Disease Study Report No. 28.

PubMed

Cukras, Catherine; Agrón, Elvira; Klein, Michael L; Ferris, Frederick L; Chew, Emily Y; Gensler, Gary; Wong, Wai T

2010-03-01

To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD). Multicenter, clinic-based, prospective cohort study. Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED. Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan-Meier analyses of progression to advanced AMD and of moderate vision loss (> or =15 letters compared with baseline) were performed. Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing > or =15 letters). A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by > or =15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters ( approximately 20/30) at baseline to 61 letters ( approximately 20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes. The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD, progressive development of pigmentary changes and calcified drusen were observed. Decline of visual acuity is a common outcome, with or without progression to advanced forms of AMD. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

HUMAN HtrA1 IN THE ARCHIVED EYES WITH AGE-RELATED MACULAR DEGENERATION

PubMed Central

Chan, Chi-Chao; Shen, Defen; Zhou, Min; Ross, Robert J.; Ding, Xiaoyan; Zhang, Kang; Green, W. Richard; Tuo, Jingsheng

2007-01-01

Purpose HtrA1 belongs to the high temperature requirement factor A family of serine proteases, which are involved in protein quality control and cell fate. A single-nucleotide polymorphism (SNP), rs11200638, in the promoter of HtrA1 at chromosome 10q26 is reported as a likely causal variant for age-related macular degeneration (AMD). The SNP is located in the regulatory region and increases production of HtrA1 protein. This study investigates HtrA1 expression and SNP genotypes in archived ocular slides with AMD. Methods Macular, nonretinal, and peripheral retinal cells were microdissected from archived slides from 57 eyes with AMD and 16 age-matched, non-AMD controls. HtrA1 rs11200638 SNP genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. HtrA1 transcripts were measured using real-time reverse transcriptase–PCR. HtrA1 protein expression was evaluated using avidin-biotin complex immunohistochemistry. Results HtrA1 (G/A) SNP was successfully genotyped in 52 AMD cases and 13 non-AMD subjects. The frequencies of the risk allele (A) were 55 of 104 (52.9%) and 8 of 26 (30.8%) in AMD and control groups, respectively. HtrA1 mRNA was detected in normal peripheral and macular retinas, higher in the periphery than maculae. HtrA1 mRNA was much higher in the macula and a lot lower in the periphery of the AMD eyes as compared to control eyes. HtrA1 protein was expressed in normal retinal vascular endothelia and retinal pigment epithelia. Intense immunoreaction against HtrA1 was found in AMD lesions, slightly more in wet than dry AMD lesions. Conclusion This study successfully analyzes HtrA1 SNP and transcript expression in microdissected cells from archived paraffin fixed slides. Up-regulation of HtrA1 is detected in the macular lesions of AMD eyes. The data further suggest that rs11200638 in HtrA1 promoter is associated with AMD development. PMID:18427598

A prospective study of common variants in the RAR-related orphan receptor alpha (RORalpha) gene and risk of neovascular age-related macular degeneration

PubMed Central

Schaumberg, Debra A.; Chasman, Daniel; Morrison, Margaux A.; Adams, Scott M.; Guo, Qun; Hunter, David J.; Hankinson, Susan E.; DeAngelis, Margaret M.

2010-01-01

Objectives The RAR-related orphan receptor alpha (RORalpha) gene is implicated as a candidate for age-related macular degeneration (AMD) through a previous microarray expression study, linkage data, biological plausibility, and two clinic-based cross sectional studies. We aimed to determine if common variants in RORalpha predict future risk of neovascular AMD. Methods We measured genotypes for 18 variants in intron 1 of the RORalpha gene among 164 cases who developed neovascular AMD and 485 age- and sex-matched controls in a prospective nested case-control study within the Nurses’ Health Study and the Health Professionals Follow-up Study. We determined the incidence rate ratios (IRR) and 95% confidence intervals (CI) for neovascular AMD for each variant, and examined interactions with other AMD-associated variants and modifiable risk factors. Results We identified a single SNP (rs12900948) that was significantly associated with increased incidence of neovascular AMD. Participants with one and two copies of the “G” allele were 1.73 (CI= 1.32–2.27) and 2.99 (CI=1.74–5.14) times more likely to develop neovascular AMD. Individuals homozygous for both the “G” allele of rs12900948 and ARMS2 A69S had a 40.8-fold increased risk of neovascular AMD (CI=10.1–164; P for interaction=0.017). Cigarette smokers who carried two copies of the “G” allele had a 9.89-fold risk of neovascular AMD, but the interaction was not significant (P=0.08). We identified a significant AMD-associated haplotype block containing SNPs rs730754, rs8034864, and rs12900948, with P-values for ACA=1.16 × 10−9, ACG=5.85 × 10−12, and GAA=0.0001 when compared to all other haplotypes. Conclusion Common variants and haplotypes within the RORalpha gene appear to act synergistically with the ARMS2 A69S polymorphism to increase risk of neovascular AMD. These data add further evidence of a high level of complexity linking genetic and modifiable risk factors to AMD development and should help efforts at risk prediction. PMID:21060049

Five-year follow-up of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD)

NASA Astrophysics Data System (ADS)

Koev, K.; Avramov, L.; Borissova, E.

2018-03-01

The objective of this study was to examine long-term effects of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD). The research was implemented for a period of five years. For LLLT, a He-Ne Laser with continuous emission at 633 nm (0.1 mW/cm2) was used in patients with AMD of all stages (dry to wet exudative forms were included). In total, 33 patients (16 men and 17 women – 66 eyes) with AMD of various stages and a mean age of 68.7 ± 4.2 years were included in the study. Progressive, exudative AMD was diagnosed in 8 eyes. 58 eyes had drusen or were depigmented. Laser radiation was applied transpupillary to the macula for six times for three minutes once in two days; 22 patients with AMD (44 eyes) were randomly selected to receive mock treatment (control group 10 men and 12 women with a mean age of 69.3 ± 4.8 years). The visual acuity was followed for a five-year period. The perimetry and Amsler test were used to screen central scotomas. The fluorescein angiography of AMD and the control groups was examined. The visual acuity remained unchanged in all patients in the control group. There was a statistically significant increase in the visual acuity (p<0.001, end of study versus baseline) for AMD patients for the period of five years after the treatment. The edema and hemorrhage in the patients with progressive, exudative AMD significantly decreased. No side effects were observed during the therapy. The prevalence of metamorphopsia, scotoma in AMD group was reduced. In conclusion, this study shows that LLLT may be a novel long-lasting therapeutic option for both forms of AMD. It is a highly-effective treatment that results in a long-term improvement of the visual acuity.

A comparison of risk factors for age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese patients.

PubMed

Chen, Xiao-Li; Hu, Qin-Rui; Bai, Yu-Jing; Deng, Yu; Wang, Hai-Wei; Liu, Shan; Wang, Yin-Lin; Yue, Yan-Kun

2018-06-01

Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are important vision-threatening diseases worldwide. For effective treatment, the risk factors for the diseases merit investigation. This study aimed to compare the risk factors for nAMD vs. PCV in Chinese patients. A total of 946 participants were recruited in this case-control study, including 281 patients with nAMD, 306 patients with PCV, and 359 controls. All participants underwent comprehensive ophthalmic examinations. Information on risk factors were collected by questionnaire. Multivariate logistic regression analyses were performed to investigate the difference in risk factors between nAMD and PCV. In a subgroup of subjects, serum lipid data were obtained and analyzed. Risk factors for nAMD included older age (OR 1.03, P = 0.001), male gender (OR 1.55, P = 0.020), asthma (OR 2.50, P = 0.028), smoking (OR 1.92, P = 0.001), and family history (OR 6.82, P = 0.001), while smoking (OR 1.67, P = 0.013) was the only risk factor for PCV. Compared to patients with PCV, patients with nAMD were more likely to be older and suffer from hyperlipidemia, coronary artery disease, rheumatism, and tumor. Interestingly, higher levels of high-density lipoprotein were positively associated with PCV in the subgroup analysis (OR 7.74, P = 0.011). Besides, results were quite different between the combination of patients with nAMD and PCV and patients with nAMD or PCV alone. The risk factors for nAMD and PCV is varying with the exception of smoking. Our findings suggest that different strategies might be applied in the clinical management and scientific research on nAMD and PCV.

Tear film proteome in age-related macular degeneration.

PubMed

Winiarczyk, Mateusz; Kaarniranta, Kai; Winiarczyk, Stanisław; Adaszek, Łukasz; Winiarczyk, Dagmara; Mackiewicz, Jerzy

2018-06-01

Age-related macular degeneration (AMD) is the main reason for blindness in elderly people in the developed countries. Current screening protocols have limitations in detecting the early signs of retinal degeneration. Therefore, it would be desirable to find novel biomarkers for early detection of AMD. Development of novel biomarkers would help in the prevention, diagnostics, and treatment of AMD. Proteomic analysis of tear film has shown promise in this research area. If an optimal set of biomarkers could be obtained from accessible body fluids, it would represent a reliable way to monitor disease progression and response to novel therapies. Tear films were collected on Schirmer strips from a total of 22 patients (8 with wet AMD, 6 with dry AMD, and 8 control individuals). 2D electrophoresis was used to separate tear film proteins prior to their identification with matrix-assisted laser desorption/ionization time of flight spectrometer (MALDI-TOF/TOF) and matching with functional databases. A total of 342 proteins were identified. Most of them were previously described in various proteomic studies concerning AMD. Shootin-1, histatin-3, fidgetin-like protein 1, SRC kinase signaling inhibitor, Graves disease carrier protein, actin cytoplasmic 1, prolactin-inducible protein 1, and protein S100-A7A were upregulated in the tear film samples isolated from AMD patients and were not previously linked with this disease in any proteomic analysis. The upregulated proteins supplement our current knowledge of AMD pathogenesis, providing evidence that certain specific proteins are expressed into the tear film in AMD. As far we are aware, this is the first study to have undertaken a comprehensive in-depth analysis of the human tear film proteome in AMD patients.

Recovery of Rare Earth Elements and Yttrium from Passive-Remediation Systems of Acid Mine Drainage.

PubMed

Ayora, Carlos; Macías, Francisco; Torres, Ester; Lozano, Alba; Carrero, Sergio; Nieto, José-Miguel; Pérez-López, Rafael; Fernández-Martínez, Alejandro; Castillo-Michel, Hiram

2016-08-02

Rare earth elements and yttrium (REY) are raw materials of increasing importance for modern technologies, and finding new sources has become a pressing need. Acid mine drainage (AMD) is commonly considered an environmental pollution issue. However, REY concentrations in AMD can be several orders of magnitude higher than in naturally occurring water bodies. With respect to shale standards, the REY distribution pattern in AMD is enriched in intermediate and valuable REY, such as Tb and Dy. The objective of the present work is to study the behavior of REY in AMD passive-remediation systems. Traditional AMD passive remediation systems are based on the reaction of AMD with calcite-based permeable substrates followed by decantation ponds. Experiments with two columns simulating AMD treatment demonstrate that schwertmannite does not accumulate REY, which, instead, are retained in the basaluminite residue. The same observation is made in two field-scale treatments from the Iberian Pyrite Belt (IPB, southwest Spain). On the basis of the amplitude of this process and on the extent of the IPB, our findings suggest that the proposed AMD remediation process can represent a modest but suitable REY source. In this sense, the IPB could function as a giant heap-leaching process of regional scale in which rain and oxygen act as natural driving forces with no energy investment. In addition to having environmental benefits of its treatment, AMD is expected to last for hundreds of years, and therefore, the total reserves are practically unlimited.

Evaluating expected outcomes of acid remediation in an intensively mined Appalachian watershed.

PubMed

Watson, Andrew S; Merovich, George T; Petty, J Todd; Gutta, J Brady

2017-07-01

Assessments of watershed-based restoration efforts are rare but are essential for the science of stream restoration to advance. We conducted a watershed scale assessment of Abram Creek before and after implementation of a watershed-based plan designed to maximize ecological recovery from acid mine drainage (AMD) impairment. We surveyed water chemistry, physical habitat, benthic macroinvertebrates, and fish community structure in three stream types: AMD-impacted (14 streams), AMD-treated (13 streams), and unimpaired reference (4 streams). We used in-stream measurements to quantify ecological loss from AMD, the amount of ecological recovery expected through remediation, and the observed degree of post-treatment recovery. Sites impaired by AMD improved in water quality with AMD treatment. Dissolved metals and acidity declined significantly in treated streams, but sulfate and specific conductance did not. Likewise, sites impaired by AMD improved in bio-condition scores with AMD treatment. EPT genera increased significantly but were lower compared to unimpaired streams. We found fish at nine treated sites that had none before treatment. Community-level analyses indicated improved but altered assemblages with AMD treatment. Analysis of pre-treatment conditions indicated that only 30% of the historic fishery remained. Remediation was expected to recover 66% of the historic fishery value, and assessment of post-treatment conditions indicates that 52% of the historic fishery has been recovered after 3 years. Developing expected endpoints for restoration outcomes provides a tool to objectively evaluate successes and can guide adaptive management strategies.

Association of glutathione S-transferase pi isoform single-nucleotide polymorphisms with exudative age-related macular degeneration in a Chinese population.

PubMed

Gu, Hong; Sun, Erdan; Cui, Lei; Yang, Xiufen; Lim, Apiradee; Xu, Jun; Snellingen, Torkel; Liu, Xipu; Wang, Ningli; Liu, Ningpu

2012-10-01

To investigate the association between single-nucleotide polymorphisms in the pi isoform of glutathione S-transferase (GSTP1) gene and the risk of exudative age-related macular degeneration (AMD) in a Chinese case-control cohort. A total of 131 Chinese patients with exudative AMD and 138 control individuals were recruited. Genomic DNA was extracted from venous blood leukocytes. Two common nonsynonymous single-nucleotide polymorphisms in GSTP1 (rs1695 and rs1138272) were genotyped by polymerase chain reaction followed by allele-specific restriction enzyme digestion and direct sequencing. Significant association with exudative AMD was detected for single-nucleotide polymorphism, rs1695 (P = 0.019). The risk G allele frequencies were 21.8% in AMD patients and 12.7% in control subjects (P = 0.007). Compared with the wild-type AA genotype, odds ratio for the risk of AMD was 1.91 (95% confidence interval, 1.09-3.35) for the heterozygous AG genotype and 2.52 (95% confidence interval, 0.6-10.61) for the homozygous GG genotype. In contrast, rs1138272 was not associated with exudative AMD (P = 1.00). The risk G allele frequencies of rs1138272 were 0.4% in AMD patients and 0.4% in control subjects (P = 1.00). Our data suggest that the GSTP1 variant rs1695 moderately increases the risk of exudative AMD. The variant rs1138272 was rare and was not associated with exudative AMD in this Chinese cohort.

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

PubMed

Laíns, Inês; Miller, John B; Mukai, Ryo; Mach, Steven; Vavvas, Demetrios; Kim, Ivana K; Miller, Joan W; Husain, Deeba

2018-06-01

To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017). Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Baseline data from a multicenter, 5-year, prospective cohort study of Japanese age-related macular degeneration: an AMD2000 report.

PubMed

Tsujikawa, Akitaka; Akagi-Kurashige, Yumiko; Yuzawa, Mitsuko; Ishibashi, Tatsuro; Nakanishi, Hideo; Nakatani, Eiji; Teramukai, Satoshi; Fukushima, Masanori; Yoshimura, Nagahisa

2018-03-01

To report research participants' baseline characteristics in the AMD2000 study, a prospective, multicenter, 5-year, observational cohort study of Japanese age-related macular degeneration (AMD). The characteristics were determined using multimodal imaging. Patients with AMD were recruited at 18 clinical sites in Japan between April 2006 and March 2009. Each patient underwent a complete ophthalmic examination, including measurement of best-corrected visual acuity (Landolt chart), indirect ophthalmoscopy, slit-lamp biomicroscopy with a contact lens, optical coherence tomography imaging, fundus photography, and fluorescein and indocyanine green angiography. Four hundred sixty participants (326 men [70.9%]) were included in the study. At enrollment, 131 eyes (28.5%) had hard drusen and 125 eyes (27.2%) had soft drusen in the macular area. A total of 455 eyes (98.9%) were diagnosed as having wet AMD, and 5 eyes (1.1%), as having dry AMD. Of the 455 eyes with wet AMD, 209 eyes (45.4%) had typical AMD, 228 eyes (49.6%) had polypoidal choroidal vasculopathy (PCV), and 18 eyes (3.9%) had retinal angiomatous proliferation. The size of choroidal neovascularization (CNV) was significantly smaller with indocyanine green angiography than with fluorescein angiography (P < 0.001). Poor baseline visual acuity was associated with cystoid macular edema, older age, scar, extrafoveal macular edema, subfoveal CNV, large branching vascular network, and hard exudates. Japanese patients with AMD are predominantly male, lack drusen, and have a high rate of PCV.

The genetics of age-related macular degeneration (AMD)--Novel targets for designing treatment options?

PubMed

Grassmann, Felix; Fauser, Sascha; Weber, Bernhard H F

2015-09-01

Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop the disease is conferred by both individual as well as genetic factors with the latter being increasingly deciphered over the last decade. Therapeutically, striking advances have been made for the treatment of the neovascular form of late stage AMD while for the late stage atrophic form of the disease, which accounts for almost half of the visually impaired, there is currently no effective therapy on the market. This review highlights our current knowledge on the genetic architecture of early and late stage AMD and explores its potential for the discovery of novel, target-guided treatment options. We reflect on current clinical and experimental therapies for all forms of AMD and specifically note a persisting lack of efficacy for treatment in atrophic AMD. We further explore the current insight in AMD-associated genes and pathways and critically question whether this knowledge is suited to design novel treatment options. Specifically, we point out that known genetic factors associated with AMD govern the risk to develop disease and thus may not play a role in its severity or progression. Treatments based on such knowledge appear appropriate rather for prevention than treatment of manifest disease. As a consequence, future research in AMD needs to be greatly focused on approaches relevant to the patients and their medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

Review of nutrient actions on age-related macular degeneration.

PubMed

Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano

2014-02-01

The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Reversible Phase Transition with Ultralarge Dielectric Relaxation Behaviors in Succinimide Lithium(I) Hybrids.

PubMed

Tang, Yun-Zhi; Wang, Bin; Zhou, Hai-Tao; Chen, Shao-Peng; Tan, Yu-Hui; Wang, Chang-Feng; Yang, Chang-Shan; Wen, He-Rui

2018-02-05

Dielectric relaxations have widely applied on high permittivity capacitors, dielectric switches, ferroelectrics, pyroelectrics, and electrical insulating materials. However, few investigations of large dielectric relaxation behaviors on organic-inorganic hybrid materials have been documented before. Here we present a novel two-dimensional succinimide lithium(I) hybrid compound, [Li(PDD) 2 ClO 4 ] n , 1, (PDD = 2,5-pyrrolidinedione = succinimide) which shows reversible phase transition behavior in the vicinity of 228 K accompanied by an unusual symmetry breaking from I4 1 /amd to C2/c. X-ray single crystal diffractions analysis indicates the twist motion of pyrrolidine heterocycles, and order-disorder motion of ClO 4 - anions triggered the reversible phase transition. By means of an intuitive crystallographic model (rattling ion model), we further illustrated the mechanism of the interesting reversible phase transition. Particularly, 1 shows ultralarge dielectric relaxation behavior in the vicinity of the phase transition by its dielectric constant dependence on temperatures and frequencies as well as its Cole-Cole relation.

Assessment, water-quality trends, and options for remediation of acidic drainage from abandoned coal mines near Huntsville, Missouri, 2003-2004

USGS Publications Warehouse

Christensen, Eric D.

2005-01-01

Water from abandoned underground coal mines acidifies receiving streams in the Sugar Creek Basin and Mitchell Mine Basin near Huntsville, Missouri. A 4.35-kilometer (2.7-mile) reach of Sugar Creek has been classified as impaired based on Missouri's Water Quality Standards because of small pH values [< (less than) 6.5]. Samples collected from Sugar Creek from July 2003 to June 2004 did not have pH values outside of the specified range of 6.5 to 9.0. However, large concentrations of iron [416 to 2,320 mg/L (milligrams per liter)], manganese (8.36 to 33.5 mg/L), aluminum (0.870 to 428 mg/L), and sulfate (2,990 to 13,700 mg/L) in acidic mine drainage (AMD) from two mine springs as well as small and diffuse seeps were observed to have an effect on water quality in Sugar Creek. Metal and sulfate loads increased and pH decreased immediately downstream from Sugar Creek's confluence with the Calfee Slope and Huntsville Gob drainages that discharge AMD into Sugar Creek. Similar effects were observed in the Mitchell Mine drainage that receives AMD from a large mine spring. Comparisons of water-quality samples from this study and two previous studies by the U.S. Geological Survey in 1987-1988 and the Missouri Department of Natural Resources in 2000-2002 indicate that AMD generation in the Sugar Creek Basin and Mitchell Mine Basin is declining, but the data are insufficient to quantify any trends or time frame. AMD samples from the largest mine spring in the Calfee Slope subbasin indicated a modest but significant increase in median pH from 4.8 to 5.2 using the Wilcoxan rank-sum test (p <0.05) and a decrease in median specific conductance from 5,000 to 3,540 ?S/cm (microsiemens per centimeter at 25 degrees Celsius) during a 17-year period. AMD samples from the largest mine spring in the Mitchell Mine Basin indicated an increase in median pH values from 5.6 to 6.0 and a decrease in median specific conductance from 3,050 to 2,450 ?S/cm during the same period. Remediation of AMD at or near the sites of the three largest mine springs is geochemically feasible based on alkalinity addition rates and increased pH determined by cubitainer experiments and geochemical mixing experiments using the computer model PHREEQCI. Alkalinity values for seven cubitainer experiments conducted to simulate anoxic treatment options exceeded the targeted value for alkalinity [90 mg/L as calcium carbonate (CaCO3)] specified in Missouri's Total Maximum Daily Load program by 18 percent or more, but maximum pH values were between 6.2 and 6.3, which is less than the targeted pH value of 6.5. Treatment of AMD by mixing with stream water or sewage effluent can further increase pH as indicated by geochemical modeling, but will not totally achieve water-quality goals because of limited discharges. A combination of treatments including settling ponds, oxic or anoxic limestone drains, and possibly successive alkalinity producing systems to remediate AMD will likely be required in the Sugar Creek Basin and Mitchell Mine Basin to consistently meet Missouri's Water Quality Standards.

Visual, Musculoskeletal, and Balance Complaints in AMD: A Follow-Up Study

PubMed Central

Richter, Hans Olof

2016-01-01

Purpose. To investigate whether patients with age-related macular degeneration (AMD) run a potentially higher risk of developing visual, musculoskeletal, and balance complaints than age-matched controls with normal vision. Methods. Visual assessments, self-rated visual function, self-rated visual, musculoskeletal, and balance complaints, and perceived general health were obtained in 37 AMD patients and 18 controls, at baseline and after an average of 3.8 years later. Results. At follow-up both groups reported decreased visual acuity (VA) and visual function, but only AMD patients reported significantly increased visual, musculoskeletal, and balance complaints. Decreased VA, need for larger font size when reading, need for larger magnification, and decreased self-rated visual function were identified as risk markers for increased complaints in AMD patients. These complaints were also identified as risk markers for decreased health. For controls, decreased VA and self-reported visual function were associated with increased visual and balance complaints. Conclusions. Visual deterioration was a risk marker for increased visual, musculoskeletal, balance, and health complaints in AMD patients. Specifically, magnifying visual aids, such as CCTV, were a risk marker for increased complaints in AMD patients. This calls for early and coordinated actions to treat and prevent visual, musculoskeletal, balance, and health complaints in AMD patients. PMID:27830084

Photometric Evaluation of Soft Tissue Changes in CLP Patients: Le Fort I Advancement Osteotomy (ALO) Versus Anterior Maxillary Distraction (AMD).

PubMed

Paulose, Joby; Markose, Eldho

2014-12-01

This paper is a comparative photometric evaluation of soft tissue changes in patients with CLP associated with maxillary deficiency treated with conventional Le Fort I advancement osteotomy (ALO) and anterior maxillary distraction (AMD). Twenty patients with maxillary hypoplasia associated with cleft lip and palate who had undergone either LeFort I osteotomy or distraction osteogenesis with maxillary advancement were included in this study. Frontal and profile photographs were used to ascertain the changes post-surgically. Photographs were obtained before treatment and 1 year after surgical correction in both groups. Vertical as well as horizontal changes in pronasale was well observed in both groups. A substantial increase in nasal parameters was noted in case of AMD group in comparison to ALO group. Though maxillary advancement was quite evident in AMD and ALO groups, a significant and consistent change was observed in AMD group. Significant vertical and horizontal changes were seen with respect to subnasale and labrale superius in AMD group. The hard and soft tissue changes produced by AMD by intra oral distractors were being evaluated so far. The results of the above studies have proved the excellence of AMD over conventional osteotomies. The present study goes hand in hand with the research outcomes till date.

Population-based incidence of exudative age-related macular degeneration and ranibizumab treatment load.

PubMed

Geirsdottir, Asbjorg; Jonsson, Oskar; Thorisdottir, Sigridur; Helgadottir, Gudleif; Jonasson, Fridbert; Stefansson, Einar; Sigurdsson, Haraldur

2012-03-01

The use of intravitreal vascular endothelial growth factor antibodies for exudative age-related macular degeneration (AMD) has stressed ophthalmology services and drug budgets throughout the world. The authors study the population-based incidence of exudative AMD in Iceland and the use of intravitreal ranibizumab in a defined population. This is a prospective study of 439 consecutive patients aged 60 years and older with exudative AMD starting intravitreal ranibizumab for exudative AMD in Iceland from March 2007 to December 2009. All patients initially received three consecutive ranibizumab injections, with regular follow-up visits and re-treatment as needed. In total, 517 eyes from 439 patients received treatment for exudative AMD (mean age 79 years). The annual incidence of exudative AMD in the population 60 years and older is 0.29%. The incidence increased with advancing age, double for patients 85 years and older compared with those 75-79 years. Approximately 2400 ranibizumab injections per 100,000 persons aged 60 years and older were given each year for exudative AMD. These data allow an estimation of the incidence of exudative AMD in a Caucasian population and the treatment load with ranibizumab, which may help plan anti-vascular endothelial growth factor treatment programmes and estimate costs.

Early and intermediate age-related macular degeneration: update and clinical review.

PubMed

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.

Early and intermediate age-related macular degeneration: update and clinical review

PubMed Central

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice. PMID:29042759

Lab-scale study on the application of In-Adit-Sulfate-Reducing System for AMD control.

PubMed

Ji, S W; Kim, S J

2008-12-30

In a study of the 29 operating passive systems for acid mine drainage (AMD) treatment, 19 systems showed various performance problems. Some systems showed very low efficiency even without visible leakage or overflow. Though systems show fairly good efficiency in metal removal (mainly iron) and pH control, sulfate removal rates were very low which indicates the possibility of very poor sulfate reductions by Sulfate Reducing Bacteria (SRB). As an alternative method, In-Adit-Sulfate-Reducing System (IASRS), the method of placing the SAPS inside the adit, to have temperature constant at about 15 degrees C, was suggested. Lab-scale model experiments of IASRS were carried out. The models 1 and 2 were run at 15 degrees C and 25 degrees C, respectively. The model 1 contained about a half of COD in the beginning of the operation than that of model 2. Metal removal ratios were higher than 90% in both systems. Both systems showed the sulfate removal ratios of 23% and 27%, respectively, which were still considerably low, even though higher than those of presently operating systems. However, since the synthetic AMD used was very low in pH (2.8) and very high in sulfate concentration, if some suggested modifications were applied to the standard design, it is presumed that the sulfate removal ratio would have increased.

Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation.

PubMed

Miao, Yinglong; Sinko, William; Pierce, Levi; Bucher, Denis; Walker, Ross C; McCammon, J Andrew

2014-07-08

Accelerated molecular dynamics (aMD) simulations greatly improve the efficiency of conventional molecular dynamics (cMD) for sampling biomolecular conformations, but they require proper reweighting for free energy calculation. In this work, we systematically compare the accuracy of different reweighting algorithms including the exponential average, Maclaurin series, and cumulant expansion on three model systems: alanine dipeptide, chignolin, and Trp-cage. Exponential average reweighting can recover the original free energy profiles easily only when the distribution of the boost potential is narrow (e.g., the range ≤20 k B T) as found in dihedral-boost aMD simulation of alanine dipeptide. In dual-boost aMD simulations of the studied systems, exponential average generally leads to high energetic fluctuations, largely due to the fact that the Boltzmann reweighting factors are dominated by a very few high boost potential frames. In comparison, reweighting based on Maclaurin series expansion (equivalent to cumulant expansion on the first order) greatly suppresses the energetic noise but often gives incorrect energy minimum positions and significant errors at the energy barriers (∼2-3 k B T). Finally, reweighting using cumulant expansion to the second order is able to recover the most accurate free energy profiles within statistical errors of ∼ k B T, particularly when the distribution of the boost potential exhibits low anharmonicity (i.e., near-Gaussian distribution), and should be of wide applicability. A toolkit of Python scripts for aMD reweighting "PyReweighting" is distributed free of charge at http://mccammon.ucsd.edu/computing/amdReweighting/.

NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration

PubMed Central

Wang, Yujuan; Hanus, Jakub W.; Abu-Asab, Mones S.; Shen, Defen; Ogilvy, Alexander; Ou, Jingxing; Chu, Xi K.; Shi, Guangpu; Li, Wei; Wang, Shusheng; Chan, Chi-Chao

2016-01-01

Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis. PMID:26760997

Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation

PubMed Central

2015-01-01

Accelerated molecular dynamics (aMD) simulations greatly improve the efficiency of conventional molecular dynamics (cMD) for sampling biomolecular conformations, but they require proper reweighting for free energy calculation. In this work, we systematically compare the accuracy of different reweighting algorithms including the exponential average, Maclaurin series, and cumulant expansion on three model systems: alanine dipeptide, chignolin, and Trp-cage. Exponential average reweighting can recover the original free energy profiles easily only when the distribution of the boost potential is narrow (e.g., the range ≤20kBT) as found in dihedral-boost aMD simulation of alanine dipeptide. In dual-boost aMD simulations of the studied systems, exponential average generally leads to high energetic fluctuations, largely due to the fact that the Boltzmann reweighting factors are dominated by a very few high boost potential frames. In comparison, reweighting based on Maclaurin series expansion (equivalent to cumulant expansion on the first order) greatly suppresses the energetic noise but often gives incorrect energy minimum positions and significant errors at the energy barriers (∼2–3kBT). Finally, reweighting using cumulant expansion to the second order is able to recover the most accurate free energy profiles within statistical errors of ∼kBT, particularly when the distribution of the boost potential exhibits low anharmonicity (i.e., near-Gaussian distribution), and should be of wide applicability. A toolkit of Python scripts for aMD reweighting “PyReweighting” is distributed free of charge at http://mccammon.ucsd.edu/computing/amdReweighting/. PMID:25061441

Dry Age-Related Macular Degeneration Pharmacology

PubMed Central

Wright, Charles B.

2017-01-01

Age-related macular degeneration (AMD), the most common form of irreversible blindness in the industrially developed world, can present years before a patient begins to lose vision. For most of these patients, AMD never progresses past its early stages to the advanced forms that are principally responsible for the vast majority of vision loss. Advanced AMD can manifest as either an advanced avascular form known as geographic atrophy (GA) marked by regional retinal pigment epithelium (RPE) cell death or as an advanced form known as neovascular AMD marked by the intrusion of fragile new blood vessels into the normally avascular retina. Physicians have several therapeutic interventions available to combat neovascular AMD, but GA has no approved effective therapies as of yet. In this chapter, we will discuss the current strategies for limiting dry AMD in patients. We will also discuss previous attempts at pharmacological intervention that were tested in a clinical setting and consider reasons why these putative therapeutics did not perform successfully in large-scale trials. Despite the number of unsuccessful past trials, new pharmacological interventions may succeed. These future therapies may aid millions of AMD patients worldwide. PMID:27900609

Evaluation of N-[(11)C]methyl-AMD3465 as a PET tracer for imaging of CXCR4 receptor expression in a C6 glioma tumor model.

PubMed

Hartimath, S V; van Waarde, A; Dierckx, R A J O; de Vries, E F J

2014-11-03

The chemokine receptor CXCR4 and its ligand CXCL12 play an important role in tumor progression and metastasis. CXCR4 receptors are expressed by many cancer types and provide a potential target for treatment. Noninvasive detection of CXCR4 may aid diagnosis and improve therapy selection. It has been demonstrated in preclinical studies that positron emission tomography (PET) with a radiolabeled small molecule could enable noninvasive monitoring of CXCR4 expression. Here, we prepared N-[(11)C]methyl-AMD3465 as a new PET tracer for CXCR4. N-[(11)C]Methyl-AMD3465 was readily prepared by N-methylation with [(11)C]CH3OTf. The tracer was obtained in a 60 ± 2% yield (decay corrected), the purity of the tracer was >99%, and specific activity was 47 ± 14 GBq/μmol. Tracer stability was tested in vitro using liver microsomes and rat plasma; excellent stability was observed. The tracer was evaluated in rat C6 glioma and human PC-3 cell lines. In vitro cellular uptake of N-[(11)C]methyl-AMD3465 was receptor mediated. The effect of transition metal ions (Cu(2+), Ni(2+), and Zn(2+)) on cellular binding was examined in C6 cells, and the presence of these ions increased the cellular binding of the tracer 9-, 7-, and 3-fold, respectively. Ex vivo biodistribution and PET imaging of N-[(11)C]methyl-AMD3465 were performed in rats with C6 tumor xenografts. Both PET and biodistribution studies demonstrated specific accumulation of the tracer in the tumor (SUV 0.6 ± 0.2) and other CXCR4 expressing organs, such as lymph node (1.5 ± 0.2), liver (8.9 ± 1.0), bone marrow (1.0 ± 0.3), and spleen (1.0 ± 0.1). Tumor uptake was significantly reduced (66%, p < 0.01) after pretreatment with Plerixafor (AMD3100). Biodistribution data indicates a tumor-to-muscle ratio of 7.85 and tumor-to-plasma ratio of 1.14, at 60 min after tracer injection. Our data demonstrated that N-[(11)C]methyl-AMD3465 is capable of detecting physiologic CXCR4 expression in tumors and other CXCR4 expressing tissues. These results warrant further evaluation of N-[(11)C]methyl-AMD3465 as a potential PET tracer for CXCR4 receptor imaging.

Acute mental disorders and short and long term morbidity in patients with third degree flame burn: A population-based outcome study of 96,451 patients from the Nationwide Inpatient Sample (NIS) database (2001-2011).

PubMed

Mahendraraj, Krishnaraj; Durgan, Diane M; Chamberlain, Ronald S

2016-12-01

Although burn patients with preexisting mood disorders have been shown to have diminished clinical recovery, acute mental disorders (AMD) are often unrecognized despite a link with post-traumatic stress disorder and social maladjustment later on. This study assessed the clinical profile of a large cohort of burn patients who developed AMD compared to those with chronic mental illness (CMI) and those without mental health problems to assess the impact of AMI on burn outcomes. Admission data on 96,451 patients with third degree flame burns was abstracted from the Nationwide Inpatient Sample (NIS) Database from 2001 to 2011. AMD was defined as adjustment disorder (ICD-10 codes F43.2-F43.29) and acute stress disorder (F43.0), while CMI was defined as major depressive disorder (F33.0-F33.9) and bipolar disorder (F31.0-F31.9). Data was compared across three subgroups: AMD, CMI, and patients without any mood disorders. Categorical variables were compared using the Chi-square test, and continuous variables were compared using Student t-test and analysis of variance (ANOVA). Multivariate analysis using the "backward Wald" method was performed to calculate odds ratios (OR) and determine independent factors which increased the risk of developing AMD after burn. 979 (1%) burn patients were diagnosed with AMD, compared to 5971 (6.2%) with CMI and 89,501 (92.8%) without mood disorders at the time of the burn. Patients with AMD were significantly younger, predominantly male and Caucasian. Patients with AMD had a higher frequency of multiple third-degree burn sites. AMD patients had a significantly longer length of hospitalization and shorter actuarial survival. More AMD patients lacked social or family support, suffered from alcoholism or illicit drug abuse, and had a history of psychological trauma or self-inflicted injuries compared to other groups. After burn, 4.9% of AMD patients developed burn wound infections, 5.0% had nutritional deficiencies, 1.7% had skin graft failure, 0.7% had acute psychosis, and 3.7% had suicidal ideation, p<0.05. Multivariate analysis identified age 10-39 (OR 4.6), alcoholism (OR 1.4), drug abuse (OR 1.9), psychoses (OR 1.4), and total body surface are (TBSA) 10-39% third degree burns (OR 1.8) as independently associated with developing AMD, p<0.005. The development of AMD in burn patients is associated with poor clinical outcomes including longer hospitalization, decreased survival, and increased complication rates. Premorbid psychopathology, substance abuse and age were associated with a higher incidence AMD after burn than was the severity of the burn wound itself. Routine screening for psychological symptoms of AMD should be performed in all burn patients to avoid increased rates of short and long-term morbidity and mortality. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

miRNAs as potential therapeutic targets for age-related macular degeneration.

PubMed

Wang, Shusheng; Koster, Kyle M; He, Yuguang; Zhou, Qinbo

2012-03-01

Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.

Age-related macular degeneration: current treatments

PubMed Central

Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

2009-01-01

Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

The Role of mf-ERG in the Diagnosis and Treatment of Age-Related Macular Degeneration: Electrophysiological Features of AMD.

PubMed

Moschos, Marilita M; Nitoda, Eirini

2018-01-01

Age-related macular cegeneration (AMD) is the leading cause of visual dysfunction worldwide, affecting 9-25% of individuals between 65 and 75 years old. We have reviewed the published articles investigating the role of multifocal electroretinogram (mf-ERG) in the diagnosis and treatment of AMD. Visual evoked potentials have revealed decreased amplitudes and higher latencies in patients with AMD, while the degeneration of photoreceptors and abnormalities of retinal pigment epithelium can be identified by electro-oculogram recordings. Moreover, ERG can detect the functional abnormalities observed in AMD and evaluate each therapeutic approach. The record of local electrophysiological responses coming from different retinal areas can be accurately performed by mfERG. The accuracy of mfERG in detecting the degeneration of photoreceptors, as well the disturbances of macular function, could be useful both in the early diagnosis of AMD and the assessment of treatment efficacy.

Retinal iron homeostasis in health and disease

PubMed Central

Song, Delu; Dunaief, Joshua L.

2013-01-01

Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Since iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired retinal diseases are associated with increased iron levels. For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich's ataxia, and pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the iron exporter ceruloplasmin and its homolog hephaestin showed age-related retinal iron accumulation and retinal degeneration with features resembling human age-related macular degeneration (AMD). Post mortem AMD eyes have increased levels of iron in retina compared to age-matched healthy donors. Iron accumulation in AMD is likely to result, in part, from inflammation, hypoxia, and oxidative stress, all of which can cause iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that iron in the retinal pigment epithelium (RPE) and retina is chelatable. Iron chelation protects photoreceptors and retinal pigment epithelial cells (RPE) in a variety of mouse models. This has therapeutic potential for diminishing iron-induced oxidative damage to prevent or treat AMD. PMID:23825457

Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.

PubMed

Lückoff, Anika; Caramoy, Albert; Scholz, Rebecca; Prinz, Marco; Kalinke, Ulrich; Langmann, Thomas

2016-06-01

Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon-β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD Complete deletion of interferon-α/β receptor (Ifnar) using Ifnar1(-/-) mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser-treated Cx3cr1(Cre) (ER):Ifnar1(fl/fl) animals that allowed the tamoxifen-induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN-β therapy of laser-treated wild-type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN-β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: The National Health and Nutrition Examination Survey 2005 to 2008

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Erin W.; Schaumberg, Debra A.; Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT

Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005–2008more » National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02–2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91–2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37–8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40–5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn. - Highlights: • We examined the association of cadmium and lead with age-related macular degeneration (AMD) in U.S. adults. • Cadmium in both blood and urine was borderline significantly associated with the risk of AMD. • Blood lead was not associated with the risk of AMD. • The association between urine cadmium and AMD was stronger in whites than in blacks.« less

Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration.

PubMed

Ozawa, Yoko; Shigeno, Yuta; Nagai, Norihiro; Suzuki, Misa; Kurihara, Toshihide; Minami, Sakiko; Hirano, Eri; Shinoda, Hajime; Kobayashi, Saori; Tsubota, Kazuo

2017-08-29

Lutein and zeaxanthin are suggested micronutrient supplements to prevent the progression of age-related macular degeneration (AMD), a leading cause of blindness worldwide. To monitor the levels of lutein/zeaxanthin in the macula, macular pigment optical density (MPOD) is measured. A commercially available device (MPSII®, Elektron Technology, Switzerland), using technology based on heterochromatic flicker photometry, can measure both absolute and estimated values of MPOD. However, whether the estimated value is applicable to Asian individuals and/or AMD patients remains to be determined. The absolute and estimated values of MPOD were measured using the MPSII® device in 77 participants with a best-corrected visual acuity (BCVA) > 0.099 (logMAR score). The studied eyes included 17 young (20-29 years) healthy, 26 aged (>50 years) healthy, 18 aged and AMD-fellow, and 16 aged AMD eyes. The mean BCVA among the groups were not significantly different. Both absolute and estimated values were measurable in all eyes of young healthy group. However, absolute values were measurable in only 57.7%, 66.7%, and 43.8%, of the aged healthy, AMD-fellow, and AMD groups, respectively, and 56.7% of the eyes included in the 3 aged groups. In contrast, the estimated value was measurable in 84.6%, 88.9% and 93.8% of the groups, respectively, and 88.3% of eyes in the pooled aged group. The estimated value was correlated with absolute value in individuals from all groups by Spearman's correlation coefficient analyses (young healthy: R 2  = 0.885, P = 0.0001; aged healthy: R 2  = 0.765, P = 0.001; AMD-fellow: R 2  = 0.851, P = 0.0001; and AMD: R 2  = 0.860, P = 0.013). Using the estimated value, significantly lower MPOD values were found in aged AMD-related eyes, which included both AMD-fellow and AMD eyes, compared with aged healthy eyes by Student's t-test (P = 0.02). Absolute, in contrast to estimated, value was measurable in a limited number of aged participants; however, it was correlated with estimated value both in young and aged Asian populations with or without AMD. These results may inform future clinical studies investigating the measurement of MPOD in understanding the role of macular pigments in the pathogenesis of AMD.

Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8).

PubMed

Lechner, Judith; Chen, Mei; Hogg, Ruth E; Toth, Levente; Silvestri, Giuliana; Chakravarthy, Usha; Xu, Heping

2017-02-23

Infiltrating immune cells including monocytes/macrophages have been implicated in the pathogenesis of neovascular age-related macular degeneration (nAMD). The aim of this study was to investigate the cytokine and chemokine expression and secretion profile of peripheral blood mononuclear cells (PBMCs) from nAMD patients and the relationship between the cytokine/chemokine expression profile and clinical phenotype of nAMD, including macular fibrosis, macular atrophy or the responsiveness to anti-VEGF therapy. One hundred sixty-one nAMD patients and 43 controls were enrolled in this study. nAMD patients were divided into subgroups based on the presence/absence of (1) macular atrophy, (2) macular fibrosis and (3) responsiveness to anti-VEGF therapy; 25-30 ml of peripheral blood were obtained from all participants and 5 ml were used for serum collection, and the remaining were used for PBMC isolation using density gradient centrifugation. Intracellular cytokine expressions by PBMCs following phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation were examined using flow cytometry. Cytokine productions in lipopolysaccharides (LPS)-or 1% oxygen -treated PBMC were measured using cytometric bead array (CBA) assay. In addition, cytokine and chemokine levels in the serum were also measured by CBA assay. PBMCs from nAMD patients secreted higher levels of IL-8, CCL2 and VEGF, especially following LPS and 1% oxygen stimulation, than those from controls. 60~80% of IL-8 producing cells were CD11b + CD3 - monocytes. The percentage of CD11b + CD3 - IL-8 + was significantly increased in nAMD patients compared to controls. PBMCs from nAMD patients without macular fibrosis produced the highest levels of IL-8 and CCL2, whilst PBMCs from nAMD patients with macular atrophy produced highest levels of VEGF. In addition, PBMCs from patients who partially responded to anti-VEGF produced higher levels of IL-8 compared to the cells from complete responders. Interestingly, serum level of CCL2 was not increased in nAMD patients although there was a trend of increased IL-8 in nAMD patients. PBMCs, in particular monocytes, may contribute to CNV development in nAMD through secreting elevated levels of IL-8, CCL2 and VEGF after they are recruited to the macula. Apart from VEGF, IL-8 and CCL2 may be additional targets for nAMD management.

Oxidative stress, innate immunity, and age-related macular degeneration

PubMed Central

Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

2016-01-01

Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have previously hypothesized that the tight homeostatic control of inflammation via the innate immune system is likely critical for avoidance of disease progression. However, the presence of a multitude of potential triggers of inflammation results in a sensitive balance in which perturbations thereof would subsequently alter the inflammatory state of the retina, leading to a state of chronic inflammation and pathologic progression. In this review, we will highlight the background literature surrounding the known genetic and environmental contributors to AMD risk, as well as a discussion of the potential mechanistic interplay of these factors that lead to disease pathogenesis with particular emphasis on the delicate control of inflammatory homeostasis and the centrality of the innate immune system in this process. PMID:27239555

[Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma].

PubMed

Panova, I E; Ermak, E M; Shaimova, T A; Shaimova, V A

2016-01-01

Ocular circulation disorders are an important factor in the development of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). To date, however, there have been no studies on choroidal blood flow peculiarities in case of concurrent AMD and POAG. to determine distinctive features of choroidal blood flow characteristic of concurrent AMD and POAG and to assess their role in disease pathogenesis. Macular choroidal blood flow, including blood supply, was assessed in 54 patients (102 eyes) by means of Doppler ultrasound. Three groups were formed: group 1 - 38 eyes with both AMD and POAG; group 2 - 41 eyes with AMD and no signs of optic nerve pathology; and group 3 - 23 eyes with POAG and no signs of AMD. Groups 1 and 2 were subdivided into two subgroups each: А - atrophic AMD and B - macular drusen. The mean patient age was 78.7±8.4 years. The following parameters of choroidal blood flow were of interest: peak systolic velocity (Vps), end diastolic velocity (Ved), time-averaged maximum velocity (Vtamax), and resistance index (RI). Groups 1, 3, and 2A had an evident choroidal hypoperfusion in the macular area (decreased Vtamax) with uncompensated perfusion deficit, despite autoregulation efforts (decreased Vps, Ved, decreased or normal RI). Group 2B demonstrated a significantly higher rate of choroidal hyperperfusion (increased Vps, Ved, Vtamax, and RI). Concurrent AMD and POAG are notable for choroidal hypoperfusion in the macular area that leads to inadequate trophism of the neurosensory retina and can aggravate the course of AMD contributing to progression of its atrophic form.

Age-related macular degeneration: the importance of family history as a risk factor.

PubMed

Shahid, Humma; Khan, Jane C; Cipriani, Valentina; Sepp, Tiina; Matharu, Baljinder K; Bunce, Catey; Harding, Simon P; Clayton, David G; Moore, Anthony T; Yates, John R W

2012-03-01

Family history is considered a risk factor for age-related macular degeneration (AMD). With the advent of effective therapy for the disease, the importance of family history merits further investigation. This study quantifies the risk associated with family history, first, by a case-control study of reported family history and, second, by examining the siblings of AMD cases. The authors recruited cases with advanced AMD, spouses and siblings. All subjects were carefully phenotyped. Clinical findings in the siblings were compared with spouses. Information about family history was collected. The ORs for reported family history of AMD were calculated. Analyses were adjusted for age, smoking and genotype. 495 AMD cases, 259 spouses and 171 siblings were recruited. The OR for AMD was 27.8 (CI 3.8 to 203.0; p=0.001) with a reported family history of an affected parent and 12.0 (CI 3.7 to 38.6; p<0.0001) with a history of an affected sibling. ORs adjusted for age and smoking were higher. Examination of siblings confirmed their increased risk with 23% affected by AMD and an OR of 10.8 (4.5 to 25.8; p<0.0001). Adjusting for age increased the OR to 16.1 (6.2 to 41.8). The risk of AMD is greatly increased by having an affected first-degree relative. Those at risk need to be made aware of this and AMD patients should advise siblings and children to seek prompt ophthalmological advice if they develop visual symptoms of distortion or reduced vision.

Complement Factor D in Age-Related Macular Degeneration

PubMed Central

Stanton, Chloe M.; Yates, John R.W.; den Hollander, Anneke I.; Seddon, Johanna M.; Swaroop, Anand; Stambolian, Dwight; Fauser, Sascha; Hoyng, Carel; Yu, Yi; Atsuhiro, Kanda; Branham, Kari; Othman, Mohammad; Chen, Wei; Kortvely, Elod; Chalmers, Kevin; Hayward, Caroline; Moore, Anthony T.; Dhillon, Baljean; Ueffing, Marius

2011-01-01

Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay. Results. Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females. Conclusions. CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis. PMID:22003108

The association of aspirin use with age-related macular degeneration.

PubMed

Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Rochtchina, Elena; Wang, Jie Jin

2013-02-25

To determine whether regular aspirin use is associated with a higher risk for developing age-related macular degeneration (AMD) by using analyzed data from a 15-year prospective cohort. A prospective analysis was conducted of data from an Australian population-based cohort with 4 examinations during a 15-year period (1992-1994 to 2007-2009). Participants completed a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status, and AMD risk factors. Age-related macular degeneration was graded side-by-side from retinal photographs taken at each study visit to assess the incidence of neovascular (wet) AMD and geographic atrophy (dry AMD) according to the international AMD classification. Of 2389 baseline participants with follow-up data available, 257 individuals (10.8%) were regular aspirin users and 63 of the 2389 developed neovascular AMD. Persons who were regular aspirin users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7% in nonusers. After adjustment for age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index, persons who were regular aspirin users had a higher risk of developing neovascular AMD (odds ratio [OR], 2.46; 95% CI, 1.25-4.83). The association showed a dose-response effect (multivariate-adjusted P = .01 for trend). Aspirin use was not associated with the incidence of geographic atrophy (multivariate-adjusted OR, 0.99; 95% CI, 0.59-1.65). Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.

Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch's Membrane.

PubMed

Corominas, Jordi; Colijn, Johanna M; Geerlings, Maartje J; Pauper, Marc; Bakker, Bjorn; Amin, Najaf; Lores Motta, Laura; Kersten, Eveline; Garanto, Alejandro; Verlouw, Joost A M; van Rooij, Jeroen G J; Kraaij, Robert; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Schick, Tina; Fauser, Sascha; de Jong, Eiko K; van Duijn, Cornelia M; Hoyng, Carel B; Klaver, Caroline C W; den Hollander, Anneke I

2018-04-26

Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited. To scrutinize the role of rare protein-altering variants in AMD cause, we performed the largest WES study in AMD to date in a large European cohort consisting of 1125 AMD patients and 1361 control participants. Genome-wide case-control association study of WES data. One thousand one hundred twenty-five AMD patients and 1361 control participants. A single variant association test of WES data was performed to detect variants that are associated individually with AMD. The cumulative effect of multiple rare variants with 1 gene was analyzed using a gene-based CMC burden test. Immunohistochemistry was performed to determine the localization of the Col8a1 protein in mouse eyes. Genetic variants associated with AMD. We detected significantly more rare protein-altering variants in the COL8A1 gene in patients (22/2250 alleles [1.0%]) than in control participants (11/2722 alleles [0.4%]; P = 7.07×10 -5 ). The association of rare variants in the COL8A1 gene is independent of the common intergenic variant (rs140647181) near the COL8A1 gene previously associated with AMD. We demonstrated that the Col8a1 protein localizes at Bruch's membrane. This study supported a role for protein-altering variants in the COL8A1 gene in AMD pathogenesis. We demonstrated the presence of Col8a1 in Bruch's membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch's membrane, contributing to the accumulation of drusen and the development of AMD. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Immunology of age-related macular degeneration

PubMed Central

Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

2014-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

Immunology of age-related macular degeneration.

PubMed

Ambati, Jayakrishna; Atkinson, John P; Gelfand, Bradley D

2013-06-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population.

Development of a Candida glabrata dominant nutritional transformation marker utilizing the Aspergillus nidulans acetamidase gene (amdS).

PubMed

Fu, Jianmin; Blaylock, Morganne; Wickes, Cameron F; Welte, William; Mehrtash, Adrian; Wiederhold, Nathan; Wickes, Brian L

2016-05-01

The gene encoding Aspergillus nidulans acetamidase (amdS) was placed under control of Candida albicans ACT1 promoter and terminator sequences and then cloned into a plasmid containing C. glabrata ARS10,CEN8 or ARS10+CEN8 sequences. All plasmids transformed C. glabrata wild-type cells to acetamide+, with the ARS-only containing plasmid transforming cells at the highest frequencies (>1.0 × 10(4) transformants μg(-1)). Plasmids were rapidly lost under non-selective conditions with the frequency dependent on chromosomal element, thus recycling the acetamide- phenotype. The amdS plasmid was used to transform a set of clinical isolates resistant to a variety of antifungal drugs. All strains were successfully transformed to the acetamide+ phenotype at high frequency, confirming that this plasmid construct could be used as a simple dominant marker on virtually any strain. Gap repair experiments demonstrated that just as in Saccharomyces cerevisiae, gap repair functions efficiently inC. glabrata, suggesting that C. glabrata has numerous similarities toS. cerevisiae with regard to ease of molecular manipulation. The amdS system is inexpensive and efficient, and combined with existing C. glabrata plasmid elements, confers a high transformation frequency for C. glabrata with a phenotype that can be easily recycled. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A systematic review on zinc for the prevention and treatment of age-related macular degeneration.

PubMed

Vishwanathan, Rohini; Chung, Mei; Johnson, Elizabeth J

2013-06-12

The objective of this systematic review was to examine the evidence on zinc intake from foods and supplements in the primary prevention and treatment of AMD. Randomized controlled trials (RCTs), prospective cohort, retrospective cohort, and case-control studies that investigated zinc intake from foods and/or supplements, and AMD in men and women with a mean age of 50 years or older were included. Medline and Cochrane Central were searched from inception to February 2012 and November 2012, respectively. Data extraction and quality appraisal were done on all eligible studies. TEN STUDIES WERE INCLUDED: four RCTs, four prospective cohort, and two retrospective cohort studies. Age-related Eye Disease Study (AREDS) showed zinc treatment to significantly reduce the risk of progression to advanced AMD. The risk of visual acuity loss was of similar magnitude, but not statistically significant. Two RCTs reported statistically significant increases in visual acuity in early AMD patients and one RCT showed no effect of zinc treatment on visual acuity in advanced AMD patients. Results from six cohort studies on associations between zinc intake and incidence of AMD were inconsistent. Current evidence on zinc intake for the prevention of AMD is inconclusive. Based on the strength of AREDS, we can conclude that zinc treatment may be effective in preventing progression to advanced AMD. Zinc supplementation alone may not be sufficient to produce clinically meaningful changes in visual acuity.

A review of the evidence for dietary interventions in preventing or slowing the progression of age-related macular degeneration.

PubMed

Evans, Jennifer R; Lawrenson, John G

2014-07-01

To summarise the results of recent Cochrane systematic reviews that have investigated whether nutritional supplements prevent or slow the progression of age-related macular degeneration (AMD). There is no good evidence from randomised controlled trials that the general population should be taking antioxidant vitamin supplements to reduce their risk of developing AMD later on in life. By contrast, there is moderate quality evidence that people with AMD may experience a delay in progression by taking specific antioxidant vitamin and mineral supplements. This finding is drawn from one large randomised controlled trial conducted in the USA in a relatively well-nourished population. Although observational studies have shown that the consumption of dietary omega 3 long chain polyunsaturated fatty acids may reduce the risk of progression to advanced AMD, two recently published randomised controlled trials failed to show any benefit of omega 3 supplements on AMD progression. There is no high quality experimental evidence that nutritional supplementation is beneficial for the primary prevention of AMD. However, people with AMD may benefit from supplementation with antioxidant vitamins. There is currently no evidence to support increasing levels of omega 3 long chain polyunsaturated fatty acids in the diet for the explicit purpose of preventing or slowing the progression of AMD. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.

Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images

PubMed Central

Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

2016-01-01

Non-lethal macular diseases greatly impact patients’ life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples. PMID:28018716

Altered gene expression in dry age-related macular degeneration suggests early loss of choroidal endothelial cells.

PubMed

Whitmore, S Scott; Braun, Terry A; Skeie, Jessica M; Haas, Christine M; Sohn, Elliott H; Stone, Edwin M; Scheetz, Todd E; Mullins, Robert F

2013-01-01

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE) and choroid from early AMD and control maculas with exon-based arrays. Gene expression levels in nine human donor eyes with early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. The complement factor H (CFH) genotype was also assessed, and differential expression was analyzed regarding high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Seventy-five genes were identified as differentially expressed (raw p value <0.01; ≥50% fold change, mean log2 expression level in AMD or control ≥ median of all average gene expression values); however, no genes were significant (adj. p value <0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change <0.5; raw p value <0.01), 18 genes were identified by DAVID analysis as associated with vision or neurologic processes. The GSEA of the RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis of the CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p value=0.0008). GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout or dedifferentiation occurs early in the pathogenesis of AMD.

Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls.

PubMed

Gopinath, Bamini; Liew, Gerald; Russell, Joanna; Cosatto, Victoria; Burlutsky, George; Mitchell, Paul

2017-08-01

Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk factors for age-related macular degeneration: findings from the Andhra Pradesh eye disease study in South India.

PubMed

Krishnaiah, Sannapaneni; Das, Taraprasad; Nirmalan, Praveen K; Nutheti, Rishita; Shamanna, Bindiganavale R; Rao, Gullapalli N; Thomas, Ravi

2005-12-01

To assess prevalence, potential risk factors, and population attributable risk percentage (PAR%) for age-related macular degeneration (AMD) in the Indian state of Andhra Pradesh. A population-based study, using a stratified, random, cluster, systematic sampling strategy, was conducted in the state of Andhra Pradesh in India from 1996 to 2000. Participants from 94 clusters in one urban and three rural areas representative of the population of Andhra Pradesh underwent a detailed interview and a detailed dilated ocular evaluation by trained professionals. In this report, the authors present the prevalence estimates of AMD and examine the association of AMD with potential risk factors in persons aged 40 to 102 years (n = 3723). AMD was defined according to the international classification and grading system. Standard bivariate and multivariate analyses were performed to identify the potential risk factors for AMD. PAR% was calculated by Levin's formula. AMD was present in 71 subjects--an age-gender-area-adjusted prevalence of 1.82% (95% confidence interval [CI], 1.39%-2.25%). Risk factors that were significant in bivariate analyses were considered for multivariate logistic regression analysis. Multivariate analysis showed that the adjusted prevalence of AMD was significantly higher in those 60 years of age or older (odds ratio [OR], 3.55; 95% CI, 1.61-7.82) and history of prior cigar smoking (OR, 3.29; 95%CI, 1.42-7.57). Presence of cortical cataract and prior cataract surgery were significantly associated with increased prevalence of AMD (adjusted OR, 2.87; 95% CI, 1.57-5.26 and 3.79; 95% CI, 2.1-6.78), respectively. The prevalence of AMD was significantly lower in light alcohol drinkers (adjusted OR, 0.38; 95% CI, 0.19-0.76) compared with nondrinkers. The PAR% for hypertension and heavy cigar smoking was 10% and 14%, respectively, in this population. The prevalence of AMD in this south Indian population is similar to those reported in other developed countries. Abstinence from smoking may reduce the risk of AMD in this population.

Prevalence and the risk factors for visual impairment in age-related macular degeneration.

PubMed

Srinivasan, S; Swaminathan, G; Kulothungan, V; Raman, R; Sharma, T

2017-06-01

PurposeTo characterize the type, and the causes of visual impairment (VI) in various stages of early and late age-related macular degeneration (AMD) and the factors associated with visual impairment in subjects with AMDMethods6617 subjects ≥60 years were enumerated; 5495 (83.04%) participated in eye examination. Of which, 4791 subjects had gradable fundus images. AMD was graded per International ARM Epidemiological Study Group. Subjects underwent detailed ophthalmic exam. VI was defined per the WHO classification. Mild VI was defined as VA less than 6/12 to 6/18, moderate VI-VA less than 6/18 but up to 6/60, severe VI-VA less than 6/60 but up to 3/60 and legal blindness-VA worse than 3/60. Factors associated with VI in AMD was analyzed with univariate and logistic regression analysis.ResultsNine hundred and eighty-eight subjects were identified as having AMD (893 with early AMD and 95 with late AMD); 85% of the subjects (95% CI: 82.7-87.1) had no VI, 13.1% had mild VI (95% CI: 11.1-15.3), 0.8% had severe VI (95% CI: 0.4-1.6), 1.1% had legal blindness (95% CI: 0.6-1.9). Prevalence of any VI was 13.7% in early AMD and 27.4% in late AMD, P=0.0004; age group 65-70 years (OR=1.89, 95% CI: 1.16-3.08, P=0.011), and those ≥75 years (OR=3.67, 95% CI: 1.95-6.91, P=0.0001) had greater odds of VI compared with age group 60-64 years. Male gender was a protective factor for VI (OR=0.57, CI: 0.36-0.90, P=0.016). Cataract (31.8%) and refractive error (28.4%) accounted for a majority of the VI.ConclusionsCataract and refractive error account for a significant proportion of VI in the south Indian population with AMD. Early AMD is the third leading cause of VI. Greater age and female gender are associated with VI in subjects with AMD.

Antimicrobial Resistance in Escherichia coli Recovered from Feedlot Cattle and Associations with Antimicrobial Use

PubMed Central

Benedict, Katharine M.; Gow, Sheryl P.; McAllister, Tim A.; Booker, Calvin W.; Hannon, Sherry J.; Checkley, Sylvia L.; Noyes, Noelle R.; Morley, Paul S.

2015-01-01

The objectives of this study were to estimate the prevalence of antimicrobial resistance (AMR) and to investigate the associations between exposures to antimicrobial drugs (AMDs) and AMR in fecal non-type specific Escherichia coli (NTSEC) recovered from a large population of feedlot cattle. Two-stage random sampling was used to select individually identified cattle for enrollment, which were sampled at arrival and then a second time later in the feeding period. Advanced regression techniques were used to estimate resistance prevalences, and to investigate associations between AMD exposures in enrolled cattle and penmates and AMR identified in NTSEC recovered from the second sample set. Resistance was most commonly detected to tetracycline, streptomycin, and sulfisoxazole, and was rarely identified for critically important AMDs. All cattle were exposed to AMDs in feed, and 45% were treated parenterally. While resistance prevalence generally increased during the feeding period, most AMD exposures were not significantly associated with AMR outcomes. Exposures of enrolled cattle to tetracycline were associated with increased resistance to tetracycline and trimethoprim sulfa, while beta-lactam exposures were associated with decreased likelihood of detecting streptomycin resistance. Pen-level AMD exposure measures were not associated with resistance outcomes. These findings suggest that tetracycline treatment of feedlot cattle can be associated with modest increases in risk for recovery of resistant NTSEC, but the numerous treatments with an advanced macrolide (tulathromycin) were not associated with detectable increases in resistance in NTSEC. All cattle were exposed to in-feed treatments of tetracycline and this could limit the ability to identify the full impact of these exposures, but these exposures varied for enrolled cattle varied, providing an opportunity to evaluate a dose response. While AMD exposures were not associated with detectably increased risks for resistance to critically important AMDs, rare resistance outcomes and infrequent exposure to other important AMDs (e.g., cephalosporins) limited our ability to rigorously investigate questions regarding factors that can influence resistance to these important AMDs. PMID:26633649

Cardiovascular Disease, its Risk Factors and Treatment, and Age-related Macular Degeneration: Women’s Health Initiative Sight Exam Ancillary Study

PubMed Central

Klein, Ronald; Deng, Yingzi; Klein, Barbara E. K.; Hyman, Leslie; Seddon, Johanna; Frank, Robert N.; Wallace, Robert B.; Hendrix, Susan L.; Kuppermann, Baruch D.; Langer, Robert D.; Kuller, Lewis; Brunner, Robert; Johnson, Karen C.; Thomas, Asha M.; Haan, Mary

2010-01-01

Purpose To examine the association of cardiovascular disease (CVD), CVD risk factors, and CVD treatment with age-related macular degeneration (AMD). Design Observational analysis of a randomized clinical trial. Methods Setting The Women’s Health Initiative Sight Examination (WHISE), an ancillary study to the Women’s Health Initiative’s (WHI) clinical trial of hormone replacement therapy. Study Population 4,288 women aged 63 years and older. Observation Procedures Information on CVD and its risk factors were obtained from a standardized questionnaire and examination. Main Outcome Measure AMD as determined by standardized grading of fundus photographs. Results Prevalence of any AMD was 21.4% (n=919). Of those with AMD, 5.8% (n=53) had signs of exudative AMD (n=39) or pure geographic atrophy (n=14), limiting the power to examine associations. Significant associations between late AMD and CVD risk factors were (odds ratio [OR], 95% confidence interval [CI]) older age (1.19, 1.13, 1.27, p < 0.0001), more pack years smoked (1.02 per pack-year smoked, 1.003, 1.03, p = 0.01), systolic blood pressure (0.84 per 10 mmHg, 0.71, 0.995, p = 0.04), report of taking calcium channel blockers (CCB) (2.49, 1.21, 5.12, p = 0.04), self-reported history of diabetes (2.00, 1.01, 3.96, p = 0.05), and greater body mass index (1.05 per 1 kg/m2, 1.001, 1.10, p = 0.05). History of myocardial infarction, stroke, use of statins, or white blood cell were not associated with AMD. Conclusions Results suggest that smoking, use of CCBs, diabetes, and obesity are risk factors for late AMD in women. However, the association of late AMD with systolic blood pressure and the effects of other CVD risk factors on early AMD need to be further explored. PMID:17317391

How does age-related macular degeneration affect real-world visual ability and quality of life? A systematic review.

PubMed

Taylor, Deanna J; Hobby, Angharad E; Binns, Alison M; Crabb, David P

2016-12-02

To review systematically the evidence of age-related macular degeneration (AMD) affecting real-world visual ability and quality of life (QoL). To explore trends in specific topics within this body of the literature. Systematic review. A systematic literature search was carried out using MEDLINE, EMBASE, CINAHL, PsycINFO, PsychARTICLES and Health and Psychosocial Instruments for articles published up to January 2015 for studies including people diagnosed with AMD, assessing real-world visual ability or QoL as an outcome. Two researchers screened studies for eligibility. Details of eligible studies including study design, characteristics of study population and outcomes measured were recorded in a data extraction table. All included studies underwent quality appraisal using the Mixed Methods Appraisal Tool 2011 Version (MMAT). From 5284 studies, 123 were eligible for inclusion. A range of approaches were identified, including performance-based methods, quantitative and qualitative patient-reported outcome measures (PROMs). AMD negatively affects tasks including mobility, face recognition, perception of scenes, computer use, meal preparation, shopping, cleaning, watching TV, reading, driving and, in some cases, self-care. There is evidence for higher rates of depression among people with AMD than among community dwelling elderly. A number of adaptation strategies have been associated with AMD of varying duration. Much of the research fails to report the type of AMD studied (59% of included studies) or the duration of disease in participants (74%). Of those that do report type studied, the breakdown is as follows: wet AMD 20%, dry AMD 4% and both types 17%. There are many publications highlighting the negative effects of AMD in various domains of life. Future research should focus on delivering some of this research knowledge into patient management and clinical trials and differentiating between the types of AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

How does age-related macular degeneration affect real-world visual ability and quality of life? A systematic review

PubMed Central

Taylor, Deanna J; Hobby, Angharad E; Binns, Alison M; Crabb, David P

2016-01-01

Objectives To review systematically the evidence of age-related macular degeneration (AMD) affecting real-world visual ability and quality of life (QoL). To explore trends in specific topics within this body of the literature. Design Systematic review. Methods A systematic literature search was carried out using MEDLINE, EMBASE, CINAHL, PsycINFO, PsychARTICLES and Health and Psychosocial Instruments for articles published up to January 2015 for studies including people diagnosed with AMD, assessing real-world visual ability or QoL as an outcome. Two researchers screened studies for eligibility. Details of eligible studies including study design, characteristics of study population and outcomes measured were recorded in a data extraction table. All included studies underwent quality appraisal using the Mixed Methods Appraisal Tool 2011 Version (MMAT). Results From 5284 studies, 123 were eligible for inclusion. A range of approaches were identified, including performance-based methods, quantitative and qualitative patient-reported outcome measures (PROMs). AMD negatively affects tasks including mobility, face recognition, perception of scenes, computer use, meal preparation, shopping, cleaning, watching TV, reading, driving and, in some cases, self-care. There is evidence for higher rates of depression among people with AMD than among community dwelling elderly. A number of adaptation strategies have been associated with AMD of varying duration. Much of the research fails to report the type of AMD studied (59% of included studies) or the duration of disease in participants (74%). Of those that do report type studied, the breakdown is as follows: wet AMD 20%, dry AMD 4% and both types 17%. Conclusions There are many publications highlighting the negative effects of AMD in various domains of life. Future research should focus on delivering some of this research knowledge into patient management and clinical trials and differentiating between the types of AMD. PMID:27913556

Fish Consumption and Age-Related Macular Degeneration Incidence: A Meta-Analysis and Systematic Review of Prospective Cohort Studies.

PubMed

Zhu, Wei; Wu, Yan; Meng, Yi-Fang; Xing, Qian; Tao, Jian-Jun; Lu, Jiong

2016-11-22

The association between fish consumption and risk of age-related macular degeneration (AMD) is still unclear. The aim of the current meta-analysis and systematic review was to quantitatively evaluate findings from observational studies on fish consumption and the risk of AMD. Relevant studies were identified by searching electronic databases (Medline and EMBASE) and reviewing the reference lists of relevant articles up to August, 2016. Prospective cohort studies that reported relative risks (RRs) and 95% confidence intervals (CIs) for the link between fish consumption and risk of AMD were included. A total of 4202 cases with 128,988 individuals from eight cohort studies were identified in the current meta-analysis. The meta-analyzed RR was 0.76 (95% CI, 0.65-0.90) when any AMD was considered. Subgroup analyses by AMD stages showed that fish consumption would reduce the risk of both early (RR, 0.83; 95% CI, 0.72-0.96) and late (RR; 0.76; 95% CI, 0.60-0.97) AMD. When stratified by the follow-up duration, fish consumption was a protective factor of AMD in both over 10 years ( n = 5; RR, 0.81; 95% CI, 0.67-0.97) and less than 10 years ( n = 3; RR, 0.70; 95% CI, 0.51 to 0.97) follow-up duration. Stratified analyses by fish type demonstrated that dark meat fish (RR, 0.68, 95% CI, 0.46-0.99), especially tuna fish (RR, 0.58; 95% CI, 95% CI, 0.47-0.71) intake was associated with reduced AMD risk. Evidence of a linear association between dose of fish consumption and risk of AMD was demonstrated. The results of this meta-analysis demonstrated that fish consumption can reduce AMD risk. Advanced, well-designed, randomized clinical trials are required in order to validate the conclusions in this study.

Stem cell therapies for age-related macular degeneration: the past, present, and future.

PubMed

Dang, Yalong; Zhang, Chun; Zhu, Yu

2015-01-01

In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.

Recent Developments for Remediating Acidic Mine Waters Using Sulfidogenic Bacteria

PubMed Central

Bitencourt, José A. P.; Sahoo, Prafulla K.; Alves, Joner Oliveira; Siqueira, José O.

2017-01-01

Acidic mine drainage (AMD) is regarded as a pollutant and considered as potential source of valuable metals. With diminishing metal resources and ever-increasing demand on industry, recovering AMD metals is a sustainable initiative, despite facing major challenges. AMD refers to effluents draining from abandoned mines and mine wastes usually highly acidic that contain a variety of dissolved metals (Fe, Mn, Cu, Ni, and Zn) in much greater concentration than what is found in natural water bodies. There are numerous remediation treatments including chemical (lime treatment) or biological methods (aerobic wetlands and compost bioreactors) used for metal precipitation and removal from AMD. However, controlled biomineralization and selective recovering of metals using sulfidogenic bacteria are advantageous, reducing costs and environmental risks of sludge disposal. The increased understanding of the microbiology of acid-tolerant sulfidogenic bacteria will lead to the development of novel approaches to AMD treatment. We present and discuss several important recent approaches using low sulfidogenic bioreactors to both remediate and selectively recover metal sulfides from AMD. This work also highlights the efficiency and drawbacks of these types of treatments for metal recovery and points to future research for enhancing the use of novel acidophilic and acid-tolerant sulfidogenic microorganisms in AMD treatment. PMID:29119111

Towards a Formal Model of the X86 ISA

DTIC Science & Technology

2012-03-30

implies (and (natp i) (natp j) (< i *2^27*)) 101 (equal (nth i (nth *mem-tablei* (initialize-mem-table j x86-64))) (if (<= j i) 1 (nth i (nth *mem...for a MOV instruction ; targeting a GPR ; see Intel 2.2.1.5, p. 2-14, and see AMD Vol. 3 Sec. 1.6 ; (p. 24), which restricts 64-bit immediates to "MOV...instructions that load ; GPRs ". And see AMD Vol. 1 Sec. 3.2.3.3 ("Immediate Operand Size"), which ; specifies those opcodes as "B8h through BFh

The Age-Related Macular Degeneration Complex: Linking Epidemiology and Histopathology Using the Minnesota Grading System (The Inaugural Frederick C. Blodi Lecture).

PubMed

Olsen, Timothy W; Bottini, Alexander R; Mendoza, Pia; Grossniklausk, Hans E

2015-09-01

To describe the histopathologic findings of the four stages of age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS) using the Minnesota grading system (MGS). There are no animal models for AMD. Eye banks enable access to human tissue with AMD. The level of AMD (grades 1 through 4) as defined by AREDS is determined ex vivo using the MGS. The AREDS has the largest collection to date of prospectively gathered data on the natural history of AMD. Since the MGS uses the same clinical criteria as AREDS, the addition of histopathologic findings of graded tissue confirms important pathophysiology at each stage of AMD. Four eye bank eyes were graded according to the MGS. Only the right eyes were dissected for phenotype grading. The fellow (left) eyes were fixed for histopathologic study. The eyes were serially sectioned (7 μm) through the macula. Individual slides were examined, and a two-dimensional reconstruction of the topography of the macula was created for each donor. Selected, unstained slides were used for immunohistochemical staining. In one donor, portions of tissue were obtained for transmission electron microscopic (TEM) processing. Donor 1 had a rare hard, nodular druse (MGS1). Donor 2 had intermediate confluent drusen (MGS2). Donor 3 had numerous intermediate drusen (MGS3) in the right eye. Histopathology of the fellow left showed basal laminar deposits (BLamD), soft drusen, and an area of occult choroidal neovascularization underlying the retinal pigment epithelium (RPE) with endothelial cells (CD31-positive). Donor 4 also had MGS 3 along with reticular pseudodrusen (RPD). Histologic and TEM examination demonstrated diffuse BLamD, thickening of Bruch's membrane, hard drusen, and focal nodules underlying the RPE that corresponded to the RPD. EM examination demonstrated both BLamD and electron-dense material located just external to the elastic layer of Bruch's membrane. Eye bank eyes graded using the MGS serve as an important link to the phenotypic and epidemiologic data from the AREDS. Thus, the MGS serves as a system to study the histopathology at each stage of AMD to better understand the relevant pathophysiologic changes in disease progression.

The Age-Related Macular Degeneration Complex: Linking Epidemiology and Histopathology Using the Minnesota Grading System (The Inaugural Frederick C. Blodi Lecture)

PubMed Central

Olsen, Timothy W.; Bottini, Alexander R.; Mendoza, Pia; Grossniklausk, Hans E.

2015-01-01

Purpose To describe the histopathologic findings of the four stages of age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS) using the Minnesota grading system (MGS). Clinical Relevance There are no animal models for AMD. Eye banks enable access to human tissue with AMD. The level of AMD (grades 1 through 4) as defined by AREDS is determined ex vivo using the MGS. The AREDS has the largest collection to date of prospectively gathered data on the natural history of AMD. Since the MGS uses the same clinical criteria as AREDS, the addition of histopathologic findings of graded tissue confirms important pathophysiology at each stage of AMD. Methods Four eye bank eyes were graded according to the MGS. Only the right eyes were dissected for phenotype grading. The fellow (left) eyes were fixed for histopathologic study. The eyes were serially sectioned (7 μm) through the macula. Individual slides were examined, and a two-dimensional reconstruction of the topography of the macula was created for each donor. Selected, unstained slides were used for immunohistochemical staining. In one donor, portions of tissue were obtained for transmission electron microscopic (TEM) processing. Results Donor 1 had a rare hard, nodular druse (MGS1). Donor 2 had intermediate confluent drusen (MGS2). Donor 3 had numerous intermediate drusen (MGS3) in the right eye. Histopathology of the fellow left showed basal laminar deposits (BLamD), soft drusen, and an area of occult choroidal neovascularization underlying the retinal pigment epithelium (RPE) with endothelial cells (CD31-positive). Donor 4 also had MGS 3 along with reticular pseudodrusen (RPD). Histologic and TEM examination demonstrated diffuse BLamD, thickening of Bruch’s membrane, hard drusen, and focal nodules underlying the RPE that corresponded to the RPD. EM examination demonstrated both BLamD and electron-dense material located just external to the elastic layer of Bruch’s membrane. Conclusion Eye bank eyes graded using the MGS serve as an important link to the phenotypic and epidemiologic data from the AREDS. Thus, the MGS serves as a system to study the histopathology at each stage of AMD to better understand the relevant pathophysiologic changes in disease progression. PMID:27895380

Age-related macular degeneration

PubMed Central

Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

2011-01-01

Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

NASA Astrophysics Data System (ADS)

Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

2016-12-01

This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

Predictive models of long-term anatomic outcome in age-related macular degeneration treated with as-needed Ranibizumab.

PubMed

Gonzalez-Buendia, Lucia; Delgado-Tirado, Santiago; Sanabria, M Rosa; Fernandez, Itziar; Coco, Rosa M

2017-08-18

To analyze predictors and develop predictive models of anatomic outcome in neovascular age-related macular degeneration (AMD) treated with as-needed ranibizumab after 4 years of follow-up. A multicenter consecutive case series non-interventional study was performed. Clinical, funduscopic and OCT characteristics of 194 treatment-naïve patients with AMD treated with as-needed ranibizumab for at least 2 years and up to 4 years were analyzed at baseline, 3 months and each year until the end of the follow-up. Baseline demographic and angiographic characteristics were also evaluated. R Statistical Software was used for statistical analysis. Main outcome measure was final anatomic status. Factors associated with less probability of preserved macula were diagnosis in 2009, older age, worse vision, presence of atrophy/fibrosis, pigment epithelium detachment, and geographic atrophy/fibrotic scar/neovascular AMD in the fellow eye. Factors associated with higher probability of GA were presence of atrophy and greater number of injections, whereas male sex, worse vision, lesser change in central macular thickness and presence of fibrosis were associated with less probability of GA as final macular status. Predictive model of preserved macula vs. GA/fibrotic scar showed sensibility of 77.78% and specificity of 69.09%. Predictive model of GA vs. fibrotic scar showed sensibility of 68.89% and specificity of 72.22%. We identified predictors of final macular status, and developed two predictive models. Predictive models that we propose are based on easily harvested variables, and, if validated, could be a useful tool for individual patient management and clinical research studies.

Visualization of Dietary Patterns and Their Associations With Age-Related Macular Degeneration.

PubMed

Chiu, Chung-Jung; Chang, Min-Lee; Li, Tricia; Gensler, Gary; Taylor, Allen

2017-03-01

We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765). Using principle component analysis, two major dietary patterns and eight minor dietary patterns were characterized. Applying logistic regression in our analysis, we related dietary patterns to the prevalence of AMD. Qualitative comparative analysis by operating Boolean algebra and drawing Venn diagrams was used to visualize our findings. In general, the eight minor patterns were subsets or extensions of either one of the two major dietary patterns (Oriental and Western patterns) and consisted of fewer characteristic foods than the two major dietary patterns. Unlike the two major patterns, which were more strongly associated with both early and advanced AMD, none of the eight minors were associated with early AMD and only four minor patterns, including the Steak pattern (odds ratio comparing the highest to lowest quintile of the pattern score = 1.73 [95% confidence interval: 1.24 to 2.41; Ptrend = 0.02]), the Breakfast pattern (0.60 [0.44 to 0.82]; Ptrend = 0.004]), the Caribbean pattern (0.64 [0.47 to 0.89; Ptrend = 0.009]), and the Peanut pattern (0.64 [0.46 to 0.89; Ptrend = 0.03]), were significantly associated with advanced AMD. Our data also suggested several potential beneficial (peanuts, pizza, coffee, and tea) and harmful (salad dressing) foods for AMD. Our data indicate that a diet of various healthy foods may be optimal for reducing AMD risk. The effects of some specific foods in the context of overall diet warrant further study.

Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

PubMed Central

2010-01-01

Background Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours. Methods A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated. Results Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. Conclusions Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD. PMID:21144031

Investigating the modulation of genetic effects on late AMD by age and sex: Lessons learned and two additional loci

PubMed Central

Grassmann, Felix; Gorski, Mathias; Loss, Julika; Heid, Iris M.

2018-01-01

Late-stage age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly with a complex etiology. The most important non-modifiable risk factors for onset and progression of late AMD are age and genetic risk factors, however, little is known about the interplay between genetics and age or sex. Here, we conducted a large-scale age- and sex-stratified genome-wide association study (GWAS) using 1000 Genomes imputed genome-wide and ExomeChip data (>12 million variants). The data were established by the International Age-related Macular Degeneration Genomics Consortium (IAMDGC) from 16,144 late AMD cases and 17,832 controls. Our systematic search for interaction effects yielded significantly stronger effects among younger individuals at two known AMD loci (near CFH and ARMS2/HTRA1). Accounting for age and gene-age interaction using a joint test identified two additional AMD loci compared to the previous main effect scan. One of these two is a novel AMD GWAS locus, near the retinal clusterin-like protein (CLUL1) gene, and the other, near the retinaldehyde binding protein 1 (RLBP1), was recently identified in a joint analysis of nuclear and mitochondrial variants. Despite considerable power in our data, neither sex-dependent effects nor effects with opposite directions between younger and older individuals were observed. This is the first genome-wide interaction study to incorporate age, sex and their interaction with genetic effects for late AMD. Results diminish the potential for a role of sex in the etiology of late AMD yet highlight the importance and existence of age-dependent genetic effects. PMID:29529059

AMISH EYE STUDY: Baseline Spectral Domain Optical Coherence Tomography Characteristics of Age-Related Macular Degeneration.

PubMed

Nittala, Muneeswar G; Song, Yeunjoo E; Sardell, Rebecca; Adams, Larry D; Pan, Samuel; Velaga, Swetha B; Horst, Violet; Dana, Debra; Caywood, Laura; Laux, Renee; Fuzzell, Denise; Fuzzell, Sarada; Scott, William K; Cooke Bailey, Jessica N; Igo, Robert P; Haines, Jonathan; Pericak-Vance, Margaret A; Sadda, SriniVas R; Stambolian, Dwight

2018-05-09

To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography. Spectral domain optical coherence tomography characteristics were analyzed in subjects with AMD (with and without subretinal drusenoid deposits [SDDs]) and normal healthy cohorts. Participants' mean age was 65.2 years (SD ± 11). Color fundus photographic findings in 596 (53%) subjects (1,009 eyes) were consistent with AMD; the remaining 478 (43%) subjects showed no signs of AMD. The choroid was significantly thinner on OCT (242 ± 76 µm, P < 0.001) in those with AMD compared with those without (263 ± 63 µm). Subretinal drusenoid deposits were found in 143 eyes (7%); 11 of the 143 eyes (8%) had no other manifestations of AMD. Drusen volume (P < 0.001) and area of geographic atrophy (P < 0.001) were significantly greater, and choroid was significantly (P < 0.001) thinner in subjects with SDDs versus those without SDDs. The authors describe spectral domain optical coherence tomography characteristics in an elderly Amish population with and without AMD, including the frequency of SDD. Although relatively uncommon in this population, the authors confirmed that SDDs can be found in the absence of other features of AMD and that eyes with SDDs have thinner choroids.

Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

PubMed

Lee, Wan-Ju Annabelle; Cheng, Ching-Lan; Lee, Cheng-Han; Kao Yang, Yea-Huei; Lin, Swu-Jane; Hsieh, Cheng-Yang

2017-10-01

Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype. Copyright © 2017 John Wiley & Sons, Ltd.

Refractive Error and the Risk of Age-Related Macular Degeneration in the South Korean Population.

PubMed

Lin, Shuai-Chun; Singh, Kuldev; Chao, Daniel L; Lin, Shan C

2016-01-01

We investigated the association between refractive error and the prevalence of age-related macular degeneration (AMD) in a population-based study. This was a cross-sectional study. Right eyes were included from 14,067 participants aged 40 years and older with gradable fundus photographs and refraction data from the fourth and the fifth Korea National Health and Nutrition Examination Survey 2008 to 2011. Early and late AMD was graded based on the International Age-Related Maculopathy Epidemiological Study Group grading system. Autorefraction data were collected to calculate spherical equivalent refraction in diopters (D) and classified into 4 groups: hyperopia (≥1.0 D), emmetropia (-0.99 to 0.99 D), mild myopia (-1.0 to -2.99 D), and moderate to high myopia (≤-3.0 D). After adjustment for potential confounders, each diopter increase in spherical equivalent was associated with a 16% [odds ratio (OR), 1.16; 95% confidence interval (CI), 1.08-1.25] and 18% (OR, 1.18; 95% CI, 1.10-1.27) increased risk of any (early + late) and early AMD, respectively. Mild and moderate to high myopia were associated with lower odds of any and early AMD compared with hyperopia (any AMD: OR, 0.62; 95% CI, 0.4-0.95 for mild myopia; OR, 0.41; 95% CI, 0.21-0.81 for moderate to high myopia; early AMD: OR, 0.63; 95% CI, 0.4-0.99 for mild myopia; OR, 0.36; 95% CI, 0.16-0.77 for moderate to high myopia group). There was no association between refractive status and the likelihood of late AMD (P = 0.91). Myopia is associated with lower odds of any and early AMD, but not with late AMD in the South Korean population.

Assessment of characteristics and remedial alternatives for abandoned mine drainage : case study at Staple Bend Tunnel unit of Allegheny Portage Railroad National Historic Site, Cambria County, Pennsylvania, 2004

USGS Publications Warehouse

Cravotta, Charles A.

2005-01-01

This report describes field, laboratory, and computational methods that could be used to assess remedial strategies for abandoned mine drainage (AMD). During April-June, 2004, the assessment process was applied to AMD from bituminous coal deposits at a test site in the Staple Bend Tunnel Unit of Allegheny Portage Railroad National Historic Site (ALPO-SBTU) in Cambria County, Pennsylvania. The purpose of this study was (1) to characterize the AMD quantity and quality within the ALPO-SBTU test site; (2) to evaluate the efficacy of limestone or steel slag for neutralization of the AMD on the basis of reaction-rate measurements; and (3) to identify possible alternatives for passive or active treatment of the AMD. The data from this case study ultimately will be used by the National Park Service (NPS) to develop a site remediation plan. The approach used in this study could be applicable at other sites subject to drainage from abandoned coal or metal mines.During April 2004, AMD from 9 sources (sites1, 1Fe, Fe, 2, 3, 3B, 5, 6, and 7) at the ALPO-SBTU test site had a combined flow rate of 1,420 gallons per minute (gal/min) and flow-weighted averages for pH of 3.3, net acidity of 55 milligrams per liter (mg/L) as CaCO3, and concentrations of dissolved sulfate, aluminum, iron, and manganese of 694 mg/L, 4.4 mg/L, 0.74 mg/L, and 1.2 mg/L, respectively. These pH, net acidity, sulfate, and aluminum values exceed effluent criteria for active mines in Pennsylvania.During April-June 2004, limestone and steel slag that were locally available were tested in the laboratory for their composition, approximate surface area, and potential to neutralize samples of the AMD. Although the substrates had a similar particle-size distribution and identical calcium content (43 percent as calcium oxide), the limestone was composed of crystalline carbonates and the slag was composed of silicate glass and minerals. After a minimum of 8 hours contact between the AMD and limestone or steel slag in closed containers (cubitainers), near-neutral effluent was produced. With prolonged contact between the AMD and limestone or steel slag, the concentrations of iron, aluminum, and most dissolved trace elements in effluent from the cubitainers declined while pH was maintained greater than 6.0 and less than 9.0. The cubitainer testing demonstrated (1) lower alkalinity production but higher pH of AMD treated with steel slag compared to limestone, and (2) predictable relations between the effluent quality, detention time, and corresponding flow rate and bulk volume for a bed of crushed limestone or steel slag in an AMD passive-treatment system.The process for evaluating AMD remedial strategies at the ALPO-SBTU test site involved the computation and ranking of the metal loadings during April 2004 for each of the AMD sources and a comparison of the data on AMD flow and chemistry (alkalinity, acidity, dissolved oxygen, ferric iron, aluminum) with published criteria for selection of passive-treatment technology. Although neutralization of the AMD by reaction with limestone was demonstrated with cubitainer tests, an anoxic limestone drain (ALD) was indicated as inappropriate for any AMD source at the test site because all had excessive concentrations of dissolved oxygen and (or) aluminum. One passive-treatment scenario that was identified for the individual or combined AMD sources involved an open limestone channel (OLC) to collect the AMD source(s), a vertical flow compost wetland (VFCW) to add alkalinity, and an aerobic wetland to facilitate iron and manganese oxidation and retention of precipitated solids. Innovative passive-system designs that direct flow upward through submerged layers of limestone and/or steel slag and that incorporate siphons for automatic flushing of solids to a pond also may warrant consideration. Alternatively, an active-treatment system with a hydraulic-powered lime doser could be employed instead of the VFCW or upflow system. Now, given these data on AMD flow and chemistry and identified remedial technologies, a resource manager can use a publicly available computer program such as "AMDTreat" to evaluate the potential sizes and costs of various remedial alternatives.

Downflow limestone beds for treatment of net-acidic, oxic, iron-laden drainage from a flooded anthracite mine, Pennsylvania, USA: 2. Laboratory evaluation

USGS Publications Warehouse

Cravotta, C.A.; Ward, S.J.; Hammarstrom, J.M.

2008-01-01

Acidic mine drainage (AMD) containing elevated concentrations of dissolved iron and other metals can be neutralized to varying degrees by reactions with limestone in passive treatment systems. We evaluated the chemical and mineralogical characteristics and the effectiveness of calcitic and dolomitic limestone for the neutralization of net-acidic, oxic, iron-laden AMD from a flooded anthracite mine. The calcitic limestone, with CaCO3 and MgCO3 contents of 99.8 and <0.1 wt%, respectively, and the dolomitic limestone, with CaCO3 and MgCO3 contents of 60.3 and 40.2 wt%, were used to construct a downflow treatment system in 2003 at the Bell Mine, a large source of AMD and baseflow to the Schuylkill River in the Southern Anthracite Coalfield, in east-central Pennsylvania. In the winter of 2002-2003, laboratory neutralization-rate experiments evaluated the evolution of effluent quality during 2 weeks of continuous contact between AMD from the Bell Mine and the crushed calcitic or dolomitic limestone in closed, collapsible containers (cubitainers). The cubitainer tests showed that: (1) net-alkaline effluent could be achieved with detention times greater than 3 h, (2) effluent alkalinities and associated dissolution rates were equivalent for uncoated and Fe(OH)3-coated calcitic limestone, and (3) effluent alkalinities and associated dissolution rates for dolomitic limestone were about half those for calcitic limestone. The dissolution rate data for the cubitainer tests were used with data on the volume of effuent and surface area of limestone in the treatment system at the Bell Mine to evaluate the water-quality data for the first 1.5 years of operation of the treatment system. These rate models supported the interpretation of field results and indicated that treatment benefits were derived mainly from the dissolution of calcitic limestone, despite a greater quantity of dolomitic limestone within the treatment system. The dissolution-rate models were extrapolated on a decadal scale to indicate the expected decreases in the mass of limestone and associated alkalinities resulting from the long-term reaction of AMD with the treatment substrate. The models indicated the calcitic limestone would need to be replenished approaching the 5-year anniversary of treatment operations to maintain net-alkaline effluent quality. ?? 2008 Springer-Verlag.

Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1.

PubMed

Luo, Ling; Uehara, Hironori; Zhang, Xiaohui; Das, Subrata K; Olsen, Thomas; Holt, Derick; Simonis, Jacquelyn M; Jackman, Kyle; Singh, Nirbhai; Miya, Tadashi R; Huang, Wei; Ahmed, Faisal; Bastos-Carvalho, Ana; Le, Yun Zheng; Mamalis, Christina; Chiodo, Vince A; Hauswirth, William W; Baffi, Judit; Lacal, Pedro M; Orecchia, Angela; Ferrara, Napoleone; Gao, Guangping; Young-Hee, Kim; Fu, Yingbin; Owen, Leah; Albuquerque, Romulo; Baehr, Wolfgang; Thomas, Kirk; Li, Dean Y; Chalam, Kakarla V; Shibuya, Masabumi; Grisanti, Salvatore; Wilson, David J; Ambati, Jayakrishna; Ambati, Balamurali K

2013-06-18

Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life. DOI:http://dx.doi.org/10.7554/eLife.00324.001.

Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1

PubMed Central

Luo, Ling; Uehara, Hironori; Zhang, Xiaohui; Das, Subrata K; Olsen, Thomas; Holt, Derick; Simonis, Jacquelyn M; Jackman, Kyle; Singh, Nirbhai; Miya, Tadashi R; Huang, Wei; Ahmed, Faisal; Bastos-Carvalho, Ana; Le, Yun Zheng; Mamalis, Christina; Chiodo, Vince A; Hauswirth, William W; Baffi, Judit; Lacal, Pedro M; Orecchia, Angela; Ferrara, Napoleone; Gao, Guangping; Young-hee, Kim; Fu, Yingbin; Owen, Leah; Albuquerque, Romulo; Baehr, Wolfgang; Thomas, Kirk; Li, Dean Y; Chalam, Kakarla V; Shibuya, Masabumi; Grisanti, Salvatore; Wilson, David J; Ambati, Jayakrishna; Ambati, Balamurali K

2013-01-01

Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life. DOI: http://dx.doi.org/10.7554/eLife.00324.001 PMID:23795287

The Definition, Rationale, and Effects of Thresholding in OCT Angiography.

PubMed

Cole, Emily D; Moult, Eric M; Dang, Sabin; Choi, WooJhon; Ploner, Stefan B; Lee, ByungKun; Louzada, Ricardo; Novais, Eduardo; Schottenhamml, Julia; Husvogt, Lennart; Maier, Andreas; Fujimoto, James G; Waheed, Nadia K; Duker, Jay S

2017-01-01

To examine the definition, rationale, and effects of thresholding in OCT angiography (OCTA). A theoretical description of OCTA thresholding in combination with qualitative and quantitative analysis of the effects of OCTA thresholding in eyes from a retrospective case series. Four eyes were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was quantitatively analyzed. A theoretical thresholding model and a qualitative and quantitative description of the dependency of OCTA on thresholding level. Due to the presence of system noise, OCTA thresholding is a necessary step in forming OCTA images; however, thresholding can complicate the relationship between blood flow and OCTA signal. Thresholding in OCTA can cause significant artifacts, which should be considered when interpreting and quantifying OCTA images.

Hydrogeochemical variables regionalization--applying cluster analysis for a seasonal evolution model from an estuarine system affected by AMD.

PubMed

Grande, J A; Carro, B; Borrego, J; de la Torre, M L; Valente, T; Santisteban, M

2013-04-15

This study describes the spatial evolution of the hydrogeochemical parameters which characterise a strongly affected estuary by Acid Mine Drainage (AMD). The studied estuarine system receives AMD from the Iberian Pyrite Belt (SW Spain) and, simultaneously, is affected by the presence of an industrial chemical complex. Water sampling was performed in the year of 2008, comprising four sampling campaigns, in order to represent seasonality. The results show how the estuary can be divided into three areas of different behaviour in response to hydrogeochemical variables concentrations that define each sampling stations: on one hand, an area dominated by tidal influence; in the opposite end there is a second area including the points located in the two rivers headwaters that are not influenced by seawater; finally there is the area that can be defined as mixing zone. These areas are moved along the hydrological year due to seasonal chemical variations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protect Your Eyes: Age-Related Macular Degeneration (AMD) Facts and Prevention Tips

MedlinePlus

PROTECT YOUR EYES Age-Related Macular Degeneration ( AMD ) FACTS & PREVENTION TIPS A LEADING CAUSE OF VISION LOSS IN THE U.S . AMD is a ... Black 2% Other 89% White As the population ages, the number of cases is expected to increase ...

Distribution pattern of anthropogenic marine debris along the gastrointestinal tract of green turtles (Chelonia mydas) as implications for rehabilitation.

PubMed

Colferai, André S; Silva-Filho, Rodolfo Pinho; Martins, Aryse Moreira; Bugoni, Leandro

2017-06-15

Pollution from anthropogenic marine debris (AMD) is currently the most widely distributed and lasting anthropic impact in the marine environment, affecting hundreds of species, including all sea turtles. In this study, the patterns of AMD distribution along the gastrointestinal tract (GT) and their relationship with obstructions and faecalomas in 62 green turtles (Chelonia mydas) that died during rehabilitation in southern Brazil were determined. The GT was split in seven sections, corresponding to the natural organs and intestinal areas morphologically and physiologically distinct. Mean mass (4.24g) and area (146.74cm 2 ) of AMD in the stomach were higher than in other sections. The anterior portion of the rectum had the highest number of obstructions, followed by the stomach. AMD was associated with the obstructions, with positive correlation between faecalomas and AMD masses. Organs and subdivisions showed marked differences in susceptibility to obstructions caused by AMD, which deserves attention in clinical interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nutrition, Genes, and Age-Related Macular Degeneration: What Have We Learned from the Trials?

PubMed

Chew, Emily Y

2017-01-01

The Age-Related Eye Disease Study (AREDS) and AREDS2 provided evidence for treating persons with age-related macular degeneration (AMD) with antioxidant vitamins and minerals to reduce the risk of development of late AMD. The AREDS2 data suggest that the beta-carotene in the original AREDS supplements be replaced by lutein and zeaxanthin, providing a safer drug for those who are smokers or former smokers. Even though consuming fish reduced the risk of AMD in observational studies, the AREDS2 results showed that omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid/eicosapentaenoic acid) had no beneficial effect on AMD. Despite the major progress in the discovery of gene variants associated with AMD, the use of genetic testing to predict disease has not been clinically useful. The use of genetic testing prior to AMD therapies such as administering AREDS supplements is not recommended by the American Academy of Ophthalmology and other organizations. © 2017 S. Karger AG, Basel.

Systemic human CR2-targeted complement alternative pathway inhibitor ameliorates mouse laser-induced choroidal neovascularization.

PubMed

Rohrer, Bärbel; Coughlin, Beth; Bandyopadhyay, Mausumi; Holers, V Michael

2012-08-01

Genetic associations and the presence of complement components within pathological structures of age-related macular degeneration (AMD) have generated the hypothesis that AMD is caused by chronic local complement activation. Since the majority of activity in the common terminal pathway results from engagement of the amplification loop, the alternative pathway has been proposed as a logical therapeutic target. We recently generated a factor H (fH)-based complement inhibitor (CR2-fH) with the capacity to be "targeted" to sites of complement C3 activation. We asked whether the human therapeutic (TT30) is effective in a mouse model of AMD. Choroidal neovascularization (CNV) was induced by argon laser photocoagulation of Bruch's membrane. Every other day, mice received intravenous injections of TT30 or vehicles, and after 6 days, the presence or absence of CNV and CNV-related changes were evaluated. Area of CNV, photoreceptor cell function, gene expression for complement components and cytokines, vascular endothelial growth factor (VEGF) protein levels, and TT30 bioavailability were determined. CNV development, which has previously been shown to require local complement activation, could be reduced by intravenous TT30 delivery. Specific inhibition of the alternative pathway not only reduced angiogenesis in CNV, but also ameliorated changes in several associated disease-related biomarkers, including diminished retinal function and molecular events known to be involved in AMD such as VEGF production. After intravenous injection, TT30 localized to CNV lesion sites in the retinal pigmented epithelium-choroid. Systemic administration of TT30 was found to reduce CNV pathology. These data may open new avenues for novel systemic AMD treatment strategies.

AMD3100 treatment attenuates pulmonary angiogenesis by reducing the c-kit (+) cells and its pro-angiogenic activity in CBDL rat lungs.

PubMed

Shen, Cheng-Cheng; Chen, Bing; Gu, Jian-Teng; Ning, Jiao-Lin; Zeng, Jing; Yi, Bin; Lu, Kai-Zhi

2018-03-01

Recent studies have shown that pulmonary angiogenesis is an important pathological process in the development of hepatopulmonary syndrome (HPS), and growing evidence has indicated that Stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis is involved in pulmonary vascular disease by mediating the accumulation of c-kit+ cells. This study aimed to test the effect of AMD3100, an antagonist of CXCR4, in HPS pulmonary angiogenesis. Common bile duct ligation (CBDL) rats were used as experimental HPS model and were treated with AMD3100 (1.25mg/kg/day, i.p.) or 0.9% saline for 3weeks. The sham rats underwent common bile duct exposure without ligation. The c-kit+ cells accounts and its angiogenic-related functions, prosurvival signals, pulmonary angiogenesis and arterial oxygenation were analysed in these groups. Our results showed that pulmonary SDF-1/CXCR4, Akt, Erk and VEGF/VEGFR2 were significantly activated in CBDL rats, and the numbers of circulating and pulmonary c-kit+ cells were increased in CBDL rats compared with control rats. Additionally, the angiogenic-related functions of c-kit+ cells and pulmonary microvessel counts were also elevated in CBDL rats. CXCR4 inhibition reduced pulmonary c-kit+ cells and microvessel counts and improved arterial oxygenation within 3weeks in CBDL rats. The pulmonary prosurvival signals and pro-angiogenic activity of c-kit+ cells were also down-regulated in AMD3100-treated rats. In conclusion, AMD3100 treatment attenuated pulmonary angiogenesis in CBDL rats and prevented the development of HPS via reductions in pulmonary c-kit+ cells and inhibition of the prosurvival signals. Our study provides new insights in HPS treatment. Copyright © 2017. Published by Elsevier B.V.

Development of a diatom-based multimetric index for acid mine drainage impacted depressional wetlands.

PubMed

Riato, Luisa; Leira, Manel; Della Bella, Valentina; Oberholster, Paul J

2018-01-15

Acid mine drainage (AMD) from coal mining in the Mpumalanga Highveld region of South Africa has caused severe chemical and biological degradation of aquatic habitats, specifically depressional wetlands, as mines use these wetlands for storage of AMD. Diatom-based multimetric indices (MMIs) to assess wetland condition have mostly been developed to assess agricultural and urban land use impacts. No diatom MMI of wetland condition has been developed to assess AMD impacts related to mining activities. Previous approaches to diatom-based MMI development in wetlands have not accounted for natural variability. Natural variability among depressional wetlands may influence the accuracy of MMIs. Epiphytic diatom MMIs sensitive to AMD were developed for a range of depressional wetland types to account for natural variation in biological metrics. For this, we classified wetland types based on diatom typologies. A range of 4-15 final metrics were selected from a pool of ~140 candidate metrics to develop the MMIs based on their: (1) broad range, (2) high separation power and (3) low correlation among metrics. Final metrics were selected from three categories: similarity to reference sites, functional groups, and taxonomic composition, which represent different aspects of diatom assemblage structure and function. MMI performances were evaluated according to their precision in distinguishing reference sites, responsiveness to discriminate reference and disturbed sites, sensitivity to human disturbances and relevancy to AMD-related stressors. Each MMI showed excellent discriminatory power, whether or not it accounted for natural variation. However, accounting for variation by grouping sites based on diatom typologies improved overall performance of MMIs. Our study highlights the usefulness of diatom-based metrics and provides a model for the biological assessment of depressional wetland condition in South Africa and elsewhere. Copyright © 2017 Elsevier B.V. All rights reserved.

Peripheral Changes Associated With Delayed Dark Adaptation in Age-related Macular Degeneration.

PubMed

Laíns, Inês; Park, Dong Ho; Mukai, Ryo; Silverman, Rebecca; Oellers, Patrick; Mach, Steven; Kim, Ivana K; Vavvas, Demetrios G; Miller, Joan W; Miller, John B; Husain, Deeba

2018-06-01

To study the association between peripheral changes in age-related macular degeneration (AMD) and dark adaptation (DA). Prospective, cross-sectional study. We recruited patients with AMD and a control group (>50 years) without any vitreoretinal disease. Ultra-widefield (UWF) pseudocolor and fundus autofluorescence (FAF) were obtained, and were assessed by 2 graders for the presence of several peripheral changes in perimacular, midperipheral, and far-peripheral zones. All participants were also imaged with 7-field color fundus photographs used for AMD staging (Age-Related Eye Disease Study classification system). Both eyes of study participants were tested with a dark adaptation (DA) extended protocol (20 minutes). Multilevel mixed-effect models (accounting for correlated outcomes between 2 eyes) were used for analyses. We included 128 eyes (n = 72 patients), 75% with AMD and the remainder controls. The presence of reticular pigmentary changes in the midperipheral (ß = 4.3, P = .012) and far-peripheral zones (ß = 8.4, P < .001) was associated with delayed rod-intercept times (RITs), even after adjusting for confounding factors. The presence, number, and extent of peripheral classic drusen did not show a similar association (P ≥ .148). The presence of a mottled decreased FAF pattern in the midperipheral zone was also associated with prolonged RITs (β = 4.4, P = .031). Our results suggest an association between DA and the presence of peripheral reticular pigmentary changes, as well as the presence of a peripheral mottled decreased FAF pattern. This provides new insights on the clinical significance of peripheral changes in AMD, and their contribution to impairments on DA. Copyright © 2018 Elsevier Inc. All rights reserved.

Removal of phosphorus from wastewater using ferroxysorb sorption media produced from amd sludge

USGS Publications Warehouse

Sibrell, P.L.; Tucker, T.W.; Kehler, T.; Fletcher, J.W.

2008-01-01

Treatment of acid mine drainage (AMD), whether with lime, limestone, caustic or simple aeration, nearly always results in generation of a metal hydroxide sludge. Disposal of the sludge often constitutes a significant fraction of the operating cost for the AMD treatment plant. Research at the USGS - Leetown Science Center has shown that AMD sludge, with its high content of aluminum and iron oxides, has a high affinity of phosphorus (P). Anthropogenic sources of P are associated with eutrophication and degradation of aquatic environments, resulting in anoxic dead zones in certain sensitive waterways. In this paper, we describe a method of converting the AMD sludge from a liability into an asset - Ferroxysorb P removal media - which can be used to remove excess P from wastewater. Three different Ferroxysorb media samples were produced from differing AMD sources and tested for P removal. Adsorption isotherms confirmed that the media had a high sorption capacity for P, as high as 19,000 mg/kg. The technology was demonstrated at an active fish hatchery, where the media remained in service for over three months without stripping or regeneration. Over that period of time, the calculated P removal was 50%, even at a very low influent P concentration of 60 parts per billion. In summary, use of the AMD-derived Ferroxysorb sorption media will reduce AMD treatment costs while at the same time helping to resolve the pressing environmental issue of eutrophication and degradation of sensitive waterways.

Association of neovascular age-related macular degeneration with month and season of birth in Italy

PubMed Central

Longo, Antonio; Casuccio, Alessandra; Pani, Luca; Avitabile, Teresio; Cillino, Salvatore; Uva, Maurizio G.; Bonfiglio, Vincenza; Russo, Andrea; Parisi, Guglielmo; Cennamo, Gilda; Furino, Claudio; Parravano, Mariacristina; Xoxi, Entela; Reibaldi, Michele

2017-01-01

In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925–1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined. PMID:27997361

Association between dietary fats and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women’s Health Initiative123

PubMed Central

Parekh, Niyati; Voland, Rickie P.; Moeller, Suzen M.; Blodi, Barbara A.; Ritenbaugh, Cheryl; Chappell, Richard J.; Wallace, Robert B.; Mares, Julie A.

2011-01-01

Objective Evaluating relationships of amount and type of dietary fat to intermediate AMD. Design Women, ages 50–79, from the Women’s Health Initiative-Observational Study, with high and low lutein intakes, were recruited into the Carotenoids in Age-Related Eye Disease Study (CAREDS). Fat intake in 1994–1998 was estimated using food frequency questionnaires. AMD was assessed in 2001–2004 from stereoscopic fundus photographs. Results Intakes of omega-6 and omega-3 polyunsaturated fats (ω-6 and ω-3 PUFA), which were highly correlated (r=0.8), were associated with higher prevalence of intermediate AMD. Significant age-interactions were noted for associations with total fat, monounsaturated and saturated fat (p= 0.01–0.02). In women <75 years (n=1,325), diets high in total fat (% energy) were associated with increased prevalence of AMD (OR (95% CI) for quintile five vs. one = 1.73 (1.02–2.7; p-trend=0.10); the association was reversed in older women. Monounsaturated fat (MUFA) intakes in quintiles three through five vs. one were associated with lower prevalence of AMD in the whole population. Conclusions Overall associations of dietary fat to AMD differed by type of fat and, often, by age in this cohort. These findings contribute insights about sources of inconsistencies of fat to AMD in epidemiological studies. PMID:19901214

Microalgae-bacteria biofilms: a sustainable synergistic approach in remediation of acid mine drainage.

PubMed

Abinandan, Sudharsanam; Subashchandrabose, Suresh R; Venkateswarlu, Kadiyala; Megharaj, Mallavarapu

2018-02-01

Microalgae and bacteria offer a huge potential in delving interest to study and explore various mechanisms under extreme environments. Acid mine drainage (AMD) is one such environment which is extremely acidic containing copious amounts of heavy metals and poses a major threat to the ecosystem. Despite its extreme conditions, AMD is the habitat for several microbes and their activities. The use of various chemicals in prevention of AMD formation and conventional treatment in a larger scale is not feasible under different geological conditions. It implies that microbe-mediated approach is a viable and sustainable alternative technology for AMD remediation. Microalgae in biofilms play a pivotal role in such bioremediation as they maintain mutualism with heterotrophic bacteria. Synergistic approach of using microalgae-bacteria biofilms provides supportive metabolites from algal biomass for growth of bacteria and mediates remediation of AMD. However, by virtue of their physiology and capabilities of metal removal, non-acidophilic microalgae can be acclimated for use in AMD remediation. A combination of selective acidophilic and non-acidophilic microalgae together with bacteria, all in the form of biofilms, may be very effective for bioremediation of metal-contaminated waters. The present review critically examines the nature of mutualistic interactions established between microalgae and bacteria in biofilms and their role in removal of metals from AMDs, and consequent biomass production for the yield of biofuel. Integration of microalgal-bacterial consortia in fuel cells would be an attractive emerging approach of microbial biotechnology for AMD remediation.

The role of apolipoprotein E (rs7412 and rs429358) in age-related macular degeneration.

PubMed

Liutkeviciene, Rasa; Vilkeviciute, Alvita; Smalinskiene, Alina; Tamosiunas, Abdonas; Petkeviciene, Janina; Zaliuniene, Dalia; Lesauskaite, Vaiva

2018-05-31

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in the developed countries. The main pathological change in AMD is the formation of drusen containing 40% of lipids, dominated by esterified cholesterol (EC) and phosphatidylcholine (PC), and protein. Haplotype ε4 of apolipoprotein E (ApoE) acts as a ligand for the low-density lipoprotein receptor and is involved in the maintenance and repair of neuronal cell membranes. This study aimed to evaluate the association of AMD with ApoE gene polymorphism variants (rs7412 and rs429358). A total of 2133 subjects were enrolled in our research. The study group comprised patients with early AMD (n = 413) and exudative AMD (n = 307), and the control group enrolled randomly selected persons (n = 1413). The genotyping of ApoE (rs7412 and rs429358) was performed using the real-time polymerase chain reaction (PCR) method. Statistical analysis revealed that ApoE 4/2 genotype was less frequently observed in in older patients with exudative AMD compared to older healthy controls (0.4% vs. 4.0%, p = 0.003). Our data demonstrated that ApoE 4/2 genotype was less frequently observed in old patients (65 years and more) with exudative AMD compared to old healthy controls. It leads to hypothesis on the protective effect of ApoE 4/2 to develop AMD in the elderly.

[Promotion effect of stromal cell-derived factor 1 on the migration of epidermal stem cells in the healing process of frostbite-wound model ex vivo].

PubMed

Gan, Lu; Cao, Chuan; Li, Shi-rong; Chai, Lin-lin; Guo, Rui; Xiang, Guang-jin; Zhao, Shu-wen

2010-06-01

To study the promotion effect of stromal cell-derived factor 1 (SDF-1) on the migration of epidermal stem cells (ESC) in the healing process of frostbite-wound model ex vivo. A three-dimensional model of full-thickness frostbite of skin was constructed (with slot-like wound) out of skin equivalent. The expression of SDF-1 in wound stroma was observed with immunohistochemistry staining on post injury days (PID) 3 and 7. The model frostbite wounds were divided into control group (treated with PBS 50 microL per wound), SDF-1 group (treated with 100 ng/mL SDF-1, 50 microL per wound), and AMD3100 group [treated with 100 ng/mL AMD3100 (50 microL per wound) for 30 minutes, and then SDF-1 50 microL was added per wound]. The redistribution of ESC around wound was observed. The expression of SDF-1 in wound stroma increased gradually on PID 3 and 7. Compared with those in control and AMD3100 groups, there were more ESC and epithelial cell layers, and more integrin beta(1)-positive cells appeared at the basal layer of wound in SDF-1 group, and some of the positive cells migrated upward to epidermis. SDF-1 contributes to wound repair through promoting ESC to migrate toward and gather around wound edge. This may be one of the mechanisms of ESC participating in wound repair.

The 'Displacing Foods of Modern Commerce' Are the Primary and Proximate Cause of Age-Related Macular Degeneration: A Unifying Singular Hypothesis.

PubMed

Knobbe, Chris A; Stojanoska, Marija

2017-11-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss and blindness in developed nations. AMD is anticipated to affect 196 million people worldwide, by 2020. However, the etiology of this disease remains unknown. Aging, genetic, and environmental influences have generally been implicated as major etiologic factors. We sought to examine the hypothesis that consumption of the 'displacing foods of modern commerce,' which equate to processed, nutrient-deficient and potentially toxic foods, may be the primary and proximate cause of AMD. To evaluate this hypothesis, we ran correlative AMD prevalence data against well-known proxy markers of processed food consumption, namely, sugar and vegetable oils, in 25 nations. In twenty-one nations, published studies provided AMD prevalence data and in four Pacific Island nations, practicing ophthalmologists in the regions completed retrospective chart analyses to estimate AMD prevalence in their respective regions. To estimate AMD prevalence historically, an extensive review of published papers and ophthalmic literature was completed. This review indicates that, between the years 1851 and 1930, AMD was a medical rarity worldwide, which then rose modestly in prevalence in the 1930s in the U.S. and U.K, finally elevating to epidemic proportions by 1975 in the U.S. Numerous developed nations have followed suit in recent decades. Simultaneously, between approximately 1880 and 2009, processed, nutrient-deficient foods gradually supplanted and displaced whole, unprocessed, nutrient-dense foods in developed nations, such that by 2009, 63 percent of the American diet was made up of nutrient-deficient foods in the form of refined white flour, added sugars, vegetable oils, and artificially created trans fats. The correlative data in 25 nations shows that increasing sugar and polyunsaturated vegetable oil consumption is invariably associated with new onset or rising prevalence of AMD, generally within about 30-40years of the beginning of increasing consumption of these proxy marker processed food components. The correlative data also demonstrates that, when consumption of sugar is moderate, but "harmful vegetable oil" consumption remains extremely low or absent, the prevalence of AMD remains rare. This study supports the hypothesis that the 'displacing foods of modern commerce,' which equate to processed, nutrient-deficient, and potentially toxic foods, are the primary and proximate cause of AMD. This study also supports the conclusion that macular degeneration is entirely preventable, through ancestral dietary strategy and avoidance of processed foods. Finally, this research has implications for patients with existing early and intermediate stages of AMD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis.

PubMed

Rudnicka, Alicja R; Jarrar, Zakariya; Wormald, Richard; Cook, Derek G; Fletcher, Astrid; Owen, Christopher G

2012-03-01

To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends. Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases. Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD). Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI). Log odds and prevalence of AMD. There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8-4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3-7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age 90. Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Groundwater hydrogeochemical characteristics in rehabilitated coalmine spoils

NASA Astrophysics Data System (ADS)

Gomo, M.; Masemola, E.

2016-04-01

The investigation aims to identify and describe hydrogeochemical processes controlling the evolution of groundwater chemistry in rehabilitated coalmine spoils and their overall influence on groundwater quality at a study area located in the Karoo basin of South Africa. A good understanding of the processes that controls the evolution of the mine water quality is vital for the planning, application and management of post-mining remedial actions. The study utilises scatter plots, statistical analysis, PHREEQC hydrogeochemical modelling, stoichiometric reaction ratios analysis, and the expanded Durov diagram as complimentary tools to interpret the groundwater chemistry data collected from monitoring boreholes from 1995 to 2014. Measured pH ranging between 6-8 and arithmetic mean of 7.32 shows that the groundwater system is characterised by circumneutral hydrogeochemical conditions period. Comparison of measured groundwater ion concentrations to theoretical reaction stoichiometry identifies Dolomite-Acid Mine Drainage (AMD) neutralisation as the main hydrogeochemical process controlling the evolution of the groundwater chemistry. Hydrogeochemical modelling shows that, the groundwater has temporal variations of calcite and dolomite saturation indices characterised by alternating cycles of over-saturation and under-saturation that is driven by the release of sulphate, calcium and magnesium ions from the carbonate-AMD neutralization process. Arithmetic mean concentrations of sulphate, calcium and magnesium are in the order of 762 mg/L, 141 mg/L and 108 mg/L. Calcium and magnesium ions contribute to very hard groundwater quality conditions. Classification based on total dissolved solids (TDS), shows the circumneutral water is of poor to unacceptable quality for drinking purposes. Despite its ability to prevent AMD formation and leaching of metals, the dolomite-AMD neutralisation process can still lead to problems of elevated TDS and hardness which mines should be aware of when developing water quality management plans.

Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular Degeneration (An American Ophthalmological Society Thesis).

PubMed

van Kuijk, Frederik J G M; McPherson, Scott W; Roehrich, Heidi

2017-08-01

Understanding the apparent paradoxical role of zinc in the pathogenesis and prevention of age-related macular degeneration (AMD) has been limited by the lack of animal models for its detection in sub-retinal epithelial deposits (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1 showed drusen contained high levels of zinc, but the probe was not suitable for in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in drusen. Flat mounts of human sub-RPE tissue using the probes were analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2 (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology. Drusen are detected in greater numbers and intensity with ZPP1 compared to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human donor without ocular history, suggesting that ZPP1 might be sensitive enough to detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE deposits at 10 months of age, whereas Zinpyr-1 required 14 months. Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1. This enhanced sensitivity will allow for more insightful analysis of zinc in AMD using human specimens and mouse models. This could result in the development of a sensitive in-vivo probe to enhance research on the role zinc in drusen formation and the early clinical diagnosis of AMD.

Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice: A Novel Model for Investigating the Early Pathogenesis of Age-Related Macular Degeneration.

PubMed

Vessey, Kirstan A; Gu, Ben J; Jobling, Andrew I; Phipps, Joanna A; Greferath, Ursula; Tran, Mai X; Dixon, Michael A; Baird, Paul N; Guymer, Robyn H; Wiley, James S; Fletcher, Erica L

2017-08-01

Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Measurement of Perceived Stress in Age-Related Macular Degeneration.

PubMed

Dougherty, Bradley E; Cooley, San-San L; Davidorf, Frederick H

2017-03-01

To validate the Perceived Stress Scale (PSS) in patients with age-related macular degeneration (AMD) using Rasch analysis. Study participants with AMD were recruited from the retina service of the Department of Ophthalmology at the Ohio State University during clinical visits for treatment or observation. Visual acuity with habitual distance correction was assessed. A 10-item version of the PSS was administered in large print or by reading the items to the patient. Rasch analysis was used to investigate the measurement properties of the PSS, including fit to the model, ability to separate between people with different levels of perceived stress, category response structure performance, and unidimensionality. A total of 137 patients with a diagnosis of AMD were enrolled. The mean (±SD) age of participants was 82 ± 9 years. Fifty-four percent were female. Median Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity of the better eye was 65 letters (Snellen 20/50), with a range of approximately 20/800 to 20/15. Forty-seven percent of participants were receiving an anti-VEGF injection on the day of the study visit. The response category structure was appropriate. One item, "How often have you felt confident in your ability to handle your personal problems?" was removed due to poor fit statistics. The remaining nine items showed good fit to the model, acceptable measurement precision as assessed by the Rasch person separation statistic, and unidimensionality. There was some evidence of differential item functioning by age and visual acuity. The Perceived Stress Scale demonstrated acceptable measurement properties and may be useful for the measurement of perceived stress in patients with AMD.

EVALUATION TECHNIQUES AND TOOL DEVELOPMENT FOR FY 08 CMAQ RELEASE

EPA Science Inventory

In this task, research efforts are outlined that relate to the AMD Model Evaluation Program element and support CMAQ releases within the FY05-FY08 time period. Model evaluation serves dual purposes; evaluation is necessary to characterize the accuracy of model predictions, and e...

Involvement of a gut-retina axis in protection against dietary glycemia induced age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial cell (RPE) dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns on risk for AMD, but th...

Introduction to the issue regarding research regarding age related macular degeneration

USDA-ARS?s Scientific Manuscript database

Blindness is the second greatest fear among the elderly. Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in most industrialized nations. AMD first compromises central high acuity vision. Subsequently, all vision may be lost. AMD is a progressive retinal d...

Age-Related Macular Degeneration: Advances in Management and Diagnosis

PubMed Central

Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration.

PubMed

Gibbs, Daniel; Yang, Zhenglin; Constantine, Ryan; Ma, Xiang; Camp, Nicola J; Yang, Xian; Chen, Hayou; Jorgenson, Adam; Hau, Vincent; Dewan, Andrew; Zeng, Jiexi; Harmon, Jennifer; Buehler, Jeanette; Brand, John M; Hoh, Josephine; Cameron, D Joshua; Dixit, Manjusha; Tong, Zongzhong; Zhang, Kang

2008-02-01

Age-related macular degeneration (AMD) is a complex disorder with genetic and environmental influences. The genetic influences affecting AMD are not well understood and few genes have been consistently implicated and replicated for this disease. A polymorphism (rs11200638) in a transcription factor binding site of the HTRA1 gene has been described, in previous reports, as being most significantly associated with AMD. In this paper, we investigate haplotype association and individual polymorphic association by genotyping additional variants in the AMD risk-associated region of chromosome 10q26. We demonstrate that rs11200638 in the promoter region and rs2293870 in exon 1 of HTRA1, are among the most significantly associated variants for advanced forms of AMD.

Estrogen signalling in the pathogenesis of age-related macular degeneration.

PubMed

Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

2015-02-01

Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

Haneş and Valea Vinului (Romania) closed mines Acid Mine Drainages (AMDs)--actual condition and passive treatment remediation proposal.

PubMed

Măicăneanu, Andrada; Bedelean, Horea; Ardelean, Marius; Burcă, Silvia; Stanca, Maria

2013-10-01

Acid Mine Drainages (AMDs) from Haneş and Valea Vinului (Romania) closed mines were considered for characterization and treatment using a local zeolitic volcanic tuff, ZVT, (Măcicaş, Cluj County, Romania). Water samples were collected from two locations, before and after discharging point in case of Haneş mine, and on three horizons in case of Valea Vinului mine. Physico-chemical (pH, total solid, heavy metal ions concentration) analyses showed that the environment is strongly affected by these AMD discharges even if the mines were closed years ago. Iron, manganese and zinc were the main pollutants identified in Haneş mine AMD, while zinc is the one mainly present in case of Valea Vinului AMD. A batch technique (no stirring) in which the ZVT was put in contact with the AMD sample was proposed as a passive remediation technique. ZVT successfully remove heavy metal ion from AMD. According to heavy metal ion concentrations, removal efficiencies are reaching 100%, varying as follows, Fe(2+)>Zn(2+)>Mn(2+). When the ZVT was compared with two cationic resins (strong, SAR and weak acid, WAR) the following series was depicted, SAR>ZVT>WAR. Copyright © 2013 Elsevier Ltd. All rights reserved.

Minor improvement for intertidal seaweeds and invertebrates after acid mine drainage diversion at Britannia Beach, Pacific Canada.

PubMed

Zis, Thalia; Ronningen, Vera; Scrosati, Ricardo

2004-06-01

In December 2001, acid mine drainage (AMD) from an abandoned copper mine at Britannia Beach (British Columbia, Canada) was diverted to flow from Britannia Creek into an outfall at 30 m depth in Howe Sound. Britannia Beach was studied in early 2003 to determine whether AMD diversion resulted in improved conditions for intertidal organisms. Species number and abundance have increased at the intertidal zone since AMD diversion, although they were still lower than at an unpolluted control site nearby (Furry Creek). Survivorship and growth rates of transplanted Mytilus trossulus (mussel) have increased since AMD diversion, although they were still significantly lower than at the control site. Transplanted Fucus gardneri (seaweed) performed better than before the AMD diversion; at Britannia Beach the chlorophyll a concentration in tissues was not significantly different from that at the control site, although the concentration of chlorophyll c in tissues and the chlorophyll c to a ratio was lower than at the control site six weeks after transplantation. Britannia Beach is still subject to leaching of metals from surrounding soils, low levels of AMD coming down the creek, and AMD discharge from the deep outfall. Although there has been an improvement, the intertidal environment at Britannia Beach still seems unable to support normal growth and survival of organisms.

Diversity of the Sediment Microbial Community in the Aha Watershed (Southwest China) in Response to Acid Mine Drainage Pollution Gradients

PubMed Central

Sun, Weimin; Sun, Min; Dong, Yiran; Ning, Zengping; Xiao, Enzong; Tang, Song; Li, Jiwei

2015-01-01

Located in southwest China, the Aha watershed is continually contaminated by acid mine drainage (AMD) produced from upstream abandoned coal mines. The watershed is fed by creeks with elevated concentrations of aqueous Fe (total Fe > 1 g/liter) and SO42− (>6 g/liter). AMD contamination gradually decreases throughout downstream rivers and reservoirs, creating an AMD pollution gradient which has led to a suite of biogeochemical processes along the watershed. In this study, sediment samples were collected along the AMD pollution sites for geochemical and microbial community analyses. High-throughput sequencing found various bacteria associated with microbial Fe and S cycling within the watershed and AMD-impacted creek. A large proportion of Fe- and S-metabolizing bacteria were detected in this watershed. The dominant Fe- and S-metabolizing bacteria were identified as microorganisms belonging to the genera Metallibacterium, Aciditerrimonas, Halomonas, Shewanella, Ferrovum, Alicyclobacillus, and Syntrophobacter. Among them, Halomonas, Aciditerrimonas, Metallibacterium, and Shewanella have previously only rarely been detected in AMD-contaminated environments. In addition, the microbial community structures changed along the watershed with different magnitudes of AMD pollution. Moreover, the canonical correspondence analysis suggested that temperature, pH, total Fe, sulfate, and redox potentials (Eh) were significant factors that structured the microbial community compositions along the Aha watershed. PMID:25979900

Effect of residual monomer from polyacrylamide on head lettuce grown in peat substrate.

PubMed

Mroczek, Ewelina; Kleiber, Tomasz; Konieczny, Piotr; Waśkiewicz, Agnieszka

2015-01-01

The paper investigates the migration of the acrylamide monomer (AMD) to lettuce chosen as a test plant growing in an organic medium (peat substrate). Polyacrylamide (PAM)-based flocculant added to the growing medium contained no more than 1000 mg kg(-1) of AMD. Plants were grown with varied doses of PAM preparation (0.5-3.0 mg dm(-3) of peat substrate) to compare the results with the control sample. The determination of AMD content, chlorophyll content, weight of the lettuce head, and also analysis of macro- and micro-elements in lyophilised test material was made under the same analytical conditions. The results showed that lettuce plants absorb AMD to the leaves from the peat substrate. The AMD uptake has a negative impact on the growth of lettuce. It reduces the average fresh weight of heads and destabilises the mineral composition of the plant. Therefore, concern related to the transfer risk of the residual AMD from sludge used for organic fertilisation of edible plants still remains a crucial question from a food and consumer safety point of view. To ensure consumer safety, the fate of the AMD following the application of PAM to cropland should be carefully monitored in the whole food chain.

Recent developments in age-related macular degeneration: a review.

PubMed

Al-Zamil, Waseem M; Yassin, Sanaa A

2017-01-01

Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease "wet AMD" into a more favorable outcome.

The Association of Serum Iron-Binding Proteins and the Antioxidant Parameter Levels in Age-Related Macular Degeneration.

PubMed

Čolak, Emina; Žorić, Lepša; Radosavljević, Aleksandra; Ignjatović, Svetlana

2018-05-01

Age-related macular degeneration (AMD) is the leading cause of the irreversible central visual loss among the elderly in the developed countries. Iron is considered a potent generator of the oxidative damage whose levels increase with age, potentially exacerbating the age-related diseases. The aim of this study was to assess the serum values of iron, and iron-binding proteins (transferrin, ferritin, and haptoglobin) in patients with AMD along with the parameters of the antioxidant defense: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase, and total antioxidant status (TAS), in order to analyze the possible impact of iron and iron-binding proteins to the development of oxidative stress in AMD patients, and the association of the selected parameters with the AMD. In addition, the aim was to examine the gender differences and calculate the cutoff points of tested parameters that could be associated with AMD. A cross-sectional study included 55 AMD patients aged 71.7 ± 7.36 years and 65 aged-matched control subjects aged 70.25 ± 6.46 years. Significantly lower ferritin (P = 0.025), SOD (P = 0.026), GPx (P = 0.019), and TAS (P < 0.004) values were found in patients with AMD compared to the controls (P < 0.05). Significant association of GPx < 27 U/gHb (odds ratio [OR]: 1.13; 95% confidence interval [CI] 0.78-2.10; P = 0.049), TAS < 1.25 mmol/L (OR: 5.77; 95% CI 0.98-367.0; P < 0.000), ferritin < 84.8 pg/mL (OR: 2.52; 95% CI 1.37-4.62; P = 0.002), and haptoglobin<1.51 g/L (OR: 1.94; 95% CI 1.05-3.56; P = 0.031) was found with the AMD. According to receiver operating characteristic curve analysis, ferritin concentration <84.8 pg/L, GPx < 27 U/gHb, and TAS < 1.25 mmol/L have sufficient predictive ability for AMD. Significantly reduced capacity of the antioxidant defense system and iron-binding storage proteins (ferritin) found in AMD could have an important role in the development of increase oxidative stress in AMD patients.

Stem Cell Mobilizers: Novel Therapeutics for Acute Kidney Injury.

PubMed

Xu, Yue; Zeng, Song; Zhang, Qiang; Zhang, Zijian; Hu, Xiaopeng

2017-01-01

In the past decade, rapid developments in stem cell studies have occurred. Researchers have confirmed the plasticity of bone marrow stem cells and the repair and regeneration effects of bone marrow hematopoietic stem cells on solid organs. These findings have suggested the possibility of using bone marrow stem cell mobilizers to repair and regenerate injured organs. Recent studies on the effects of granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100) on mouse acute kidney injury models have confirmed that the use of bone marrow stem cell mobilizers may be an effective therapeutic measure. This paper summarizes studies describing the effects of G-CSF and AMD3100 on various acute kidney injury models over the past 10 years. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Viscoelastic properties of the posterior eye of normal subjects, patients with age-related macular degeneration, and pigs.

PubMed

Zhang, Zhen Huan; Pan, Meng Xin; Cai, Jia Tong; Weiland, James D; Chen, Kinon

2018-03-26

The purpose of this study is to measure, characterize, and compare the viscoelastic properties of the posterior eye of advanced dry age-related macular degeneration (AMD) patients, age-matched normal subjects, and pigs (3 groups). Ten horizontal and ten vertical strips of the macula retina and the underneath choroid and sclera were obtained for each group, respectively. They were examined by incremental stress-relaxation cycles in body-temperature saline. Mechanical response was characterized by the quasi-linear viscoelastic model. All the tissues were shown to be nonlinear viscoelastic. Stiffening and isotropization, increased relaxation, and softening and isotropization were found in AMD retina, choroid, and sclera, respectively, which are the mechanical features of the atherosclerotic process. The patients' medical records were in accordance with epidemiological studies indicating a relationship between the advanced AMD and atherosclerotic vascular disease (ASVD). Moreover, many differences were found between the viscoelastic properties of porcine and normal human retina, choroid, and sclera. The results suggest that AMD is associated with ASVD through a mechanism involving abnormal retinal, choroidal, and scleral mechanics similar to those seen in the atherosclerotic process. Moreover, researchers should be aware of mechanical differences when using porcine posterior eyes as a substitute for human posterior eyes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

Immune responses in age-related macular degeneration and a possible long-term therapeutic strategy for prevention.

PubMed

Nussenblatt, Robert B; Lee, Richard W J; Chew, Emily; Wei, Lai; Liu, Baoying; Sen, H Nida; Dick, Andrew D; Ferris, Frederick L

2014-07-01

To describe the immune alterations associated with age-related macular degeneration (AMD); and, based on these findings, to offer an approach to possibly prevent the expression of late disease. Perspective. Review of the existing literature dealing with epidemiology, models, and immunologic findings in patients. Significant genetic associations have been identified and reported, but environmentally induced (including epigenetic) changes are also an important consideration. Immune alterations include a strong interleukin 17 family signature as well as marked expression of these molecules in the eye. Oxidative stress as well as other homeostatic altering mechanisms occur throughout life. With this immune dysregulation there is a rationale for considering immunotherapy. Indeed, immunotherapy has been shown to affect the late stages of AMD. Immune dysregulation appears to be an underlying alteration in AMD, as in other diseases thought to be degenerative and attributable to aging. Para-inflammation and immunosenescence may importantly contribute to the development of disease. The role of complement factor H still needs to be better defined, but in light of its association with ocular inflammatory conditions such as sarcoidosis, it does not appear to be unique to AMD but rather may be a marker for retinal pigment epithelium function. With the strong interleukin 17 family signature and the need to treat early on in the disease process, oral tolerance may be considered to prevent disease progression. Published by Elsevier Inc.

Removal of metal from acid mine drainage using a hybrid system including a pipes inserted microalgae reactor.

PubMed

Park, Young-Tae; Lee, Hongkyun; Yun, Hyun-Shik; Song, Kyung-Guen; Yeom, Sung-Ho; Choi, Jaeyoung

2013-12-01

In this study, the microalgae culture system to combined active treatment system and pipe inserted microalgae reactor (PIMR) was investigated. After pretreated AMD in active treatment system, the effluent load to PIMR in order to Nephroselmis sp. KGE 8 culture. In experiment, effect of iron on growth and lipid accumulation in microalgae were inspected. The 2nd pretreatment effluent was economic feasibility of microalgae culture and lipid accumulation. The growth kinetics of the microalgae are modeled using logistic growth model and the model is primarily parameterized from data obtained through an experimental study where PIMR were dosed with BBM, BBM added 10 mg L(-1) iron and 2nd pretreatment effluent. Moreover, the continuous of microalgae culture in PIMR can be available. Overall, this study indicated that the use of pretreated AMD is a viable method for culture microalgae and lipid accumulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Novel Tool for the Assessment Oxidative Stress in Age-Related Macular Degeneration: Thiol/Disulfide Homeostasis Revisited.

PubMed

Arıkan Yorgun, Mücella; Toklu, Yasin; Altınkaynak, Hasan; Tanrıverdi, Burak; Ergin, Merve; Biçer, Cemile

2016-12-01

To investigate thiol/disulfide status using a novel automated assay in patients with age-related macular degeneration (AMD) compared to age-matched healthy controls. A total of 64 AMD patients [51 (79%) non-exudative, 13 (21%) exudative AMD] and 21 age-matched healthy control subjects were enrolled in this study. Plasma total thiol, native thiol, disulfide levels were measured and native thiol/disulfide ratio (TDR) was calculated using a novel spectrophotometric assay. Patients with AMD had significantly lower levels of total thiol (434.8 ± 7.0 μmol/L vs. 472.2 ± 7.9 μmol/L, p < 0.001), native thiol (393.6 ± 6.5 μmol/L vs. 437.5 ± 7.1 μmol/L, p = 0.004) compared to healthy controls. However, plasma disulfide levels were higher in AMD patients (20.6 ± 0.9 μmol/L vs. 17.3 ± 1.3 μmol/L, p = 0.113) compared to healthy controls. The TDR was not statistically different between the early AMD group and healthy controls (24.2 ± 2.3 vs. 29.5 ± 3.1, p = 0.345). However, intermediate and advanced stage AMD groups had significantly lower levels of TDR compared to healthy controls (21.6 ± 2.6 vs. 29.5 ± 3.1, p = 0.023 and 20.3 ± 1.2 vs. 29.5 ± 3.1, p = 0.005, respectively). Native TDR was significantly lower in patients with exudative and non-exudative AMD (19.9 ± 2.3 vs. 29.5 ± 3.1, p = 0.024 and 21.8 ± 1.14 vs. 29.47 ± 3.1 respectively, p = 0.011). A greater extent of thiol consumption occurred in AMD patients compared to age-matched healthy controls. However, despite the similar levels of total thiol levels between several grades of AMD, the plasma native TDR value was decreased in accordance with the severity of the disease, which reflected the disease grade better.

Vitamin D Deficiency in Community-Dwelling Elderly Is Not Associated with Age-Related Macular Degeneration.

PubMed

Cougnard-Grégoire, Audrey; Merle, Bénédicte M J; Korobelnik, Jean-Francois; Rougier, Marie-Bénédicte; Delyfer, Marie-Noëlle; Féart, Catherine; Le Goff, Mélanie; Dartigues, Jean-François; Barberger-Gateau, Pascale; Delcourt, Cécile

2015-08-01

Elderly persons are at elevated risk of vitamin D deficiency, which is involved in various health problems. However, its relation with age-related macular degeneration (AMD) is debated. We investigated factors associated with plasma 25-hydroxyvitamin D [25(OH)D] deficiency and the associations between plasma 25(OH)D concentrations and AMD in elderly subjects. Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes (ALIENOR) is a population-based study on eye diseases performed in elderly residents of Bordeaux, France. Plasma 25(OH)D concentrations were assessed from blood samples and categorized as <25 nmol/L (deficiency), 25-49 nmol/L (insufficiency), or ≥50 nmol/L (sufficiency). AMD was classified as: no AMD, early AMD, and late AMD. Associations between baseline characteristics and plasma 25(OH)D status were examined with multinomial logistic regression analysis. Associations between AMD and plasma 25(OH)D status were estimated using generalized estimating equation logistic regressions. Six hundred ninety-seven subjects with complete data were included. The prevalence of plasma 25(OH)D deficiency and insufficiency were 27.3% and 55.9%, respectively. In multivariate analysis, 25(OH)D deficiency was significantly associated with older age (P = 0.0007), females (P = 0.0007), absence of physical activity (P = 0.01), absence of vitamin D supplementation (P < 0.0001), higher plasma total cholesterol (P = 0.007), use of fibrates (P < 0.0001), lower alcohol consumption (P = 0.02), and season of blood sampling (P < 0.0001). After adjustment for these covariates and dietary omega-3 polyunsaturated fatty acid intake, smoking, and body mass index, no significant associations were found between early AMD and 25(OH)D insufficiency or deficiency (OR: 0.71, P = 0.12; OR: 0.73, P = 0.23, respectively) or with late AMD (OR: 1.04, P = 0.93; OR: 0.74, P = 0.59, respectively). These findings underline the very high prevalence of plasma 25(OH)D deficiency in this elderly population but do not support a specific role for vitamin D in AMD. © 2015 American Society for Nutrition.

Updates on the Epidemiology of Age-Related Macular Degeneration.

PubMed

Jonas, Jost B; Cheung, Chui Ming Gemmy; Panda-Jonas, Songhomitra

2017-01-01

This meta-analysis reports on current estimates of the prevalence of age-related macular degeneration (AMD) based on a review of recent meta-analyses and literature research. Within an age of 45-85 years, global prevalences of any AMD, early AMD, and late AMD were 8.7% [95% credible interval (CrI), 4.3‒17.4], 8.0% (95% CrI, 4.0‒15.5), and 0.4% (95% CrI, 0.2-0.8). Early AMD was more common in individuals of European ancestry (11.2%) than in Asians (6.8%), whereas prevalence of late AMD did not differ significantly. AMD of any type was less common in individuals of African ancestry. The number of individuals with AMD was estimated to be 196 million (95% CrI, 140‒261) in 2020 and 288 million (95% CrI, 205‒399) in 2040. The worldwide number of persons blind (presenting visual acuity < 3/60) or with moderate to severe vision impairment (MSVI; presenting visual acuity < 6/18 to 3/60 inclusive) due to macular disease in 2010 was 2.1 million [95% uncertainty interval (UI), 1.9‒2.7] individuals out of 32.4 million individuals blind and 6.0 million (95% UI, 5.2‒8.1) persons out of 191 million people with MSVI. Age-standardized prevalence of macular diseases as cause of blindness in adults aged 50+ years worldwide decreased from 0.2% (95% UI, 0.2‒0.2) in 1990 to 0.1% (95% UI, 0.1‒0.2) in 2010; as cause for MSVI, it remained mostly unchanged (1990: 0.4%; 95% UI, 0.3‒0.5; 2010: 0.4%; 95% UI, 0.4‒0.6), with no significant sex difference. In 2015, AMD was the fourth most common cause of blindness globally (in approximately 5.8% of blind individuals) and third most common cause for MSVI (3.9%). These data show the globally increasing importance of AMD. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

In situ reaction mechanism studies on the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2}-D{sub 2}O and Ti(O{sup i}Pr){sub 3}[MeC(N{sup i}Pr){sub 2}]-D{sub 2}O atomic layer deposition processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomczak, Yoann, E-mail: yoann.tomczak@helsinki.fi; Knapas, Kjell; Leskelä, Markku

2014-01-15

Reaction mechanisms in the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2}-D{sub 2}O and Ti(O{sup i}Pr){sub 3}[MeC(N{sup i}Pr){sub 2}] [also written Ti(O{sup i}Pr){sub 3}(N{sup i}Pr-Me-amd)]-D{sub 2}O atomic layer deposition processes were studied in situ with quartz crystal microbalance (QCM) and quadrupole mass spectrometry (QMS) at 275 °C. For the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2}-D{sub 2}O process, both QCM and QMS results indicated adsorption of the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2} molecule through an exchange of at least one of its –NMe{sub 2} ligands with surface hydroxyl groups. Regarding the Ti(O{sup i}Pr){sub 3}(N{sup i}Pr-Me-amd)-D{sub 2}O process, a mismatch between the QCM and QMS results revealedmore » more complex reactions: the decomposition of the [MeC(N{sup i}Pr){sub 2}] [also written (N{sup i}Pr-Me-amd)] ligand is suggested by the shape of the QCM data and the intensity of the QMS signals belonging to fragments of the [MeC(N{sup i}Pr){sub 2}] [also written (N{sup i}Pr-Me-amd)] ligand. A simple calculation model associating the growth rate per cycle of a crystalline film and the surface area taken by the ligands remaining after saturation was also used to support the decomposition of the [MeC(N{sup i}Pr){sub 2}] [also written (N{sup i}Pr-Me-amd)] ligand. The observed high growth rate is incompatible with the whole [MeC(N{sup i}Pr){sub 2}] (also written [N{sup i}Pr-Me-amd)] ligand remaining on the surface.« less

The Effects of Low-Vision Rehabilitation on Reading Speed and Depression in Age Related Macular Degeneration: A Meta-Analysis.

PubMed

Hamade, Noura; Hodge, William G; Rakibuz-Zaman, Muhammad; Malvankar-Mehta, Monali S

2016-01-01

Age related macular degeneration (AMD) is a progressive eye disease that, as of 2015, has affected 11 million people in the U.S. and 1.5 million in Canada causing central vision blindness. By 2050, this number is expected to double to 22 million. Eccentric vision is the target of low-vision rehabilitation aids and programs for patients with AMD, which are thought to improve functional performance by improving reading speed and depression. This study evaluates the effect of various low-vision rehabilitation strategies on reading speed and depression in patients 55 and older with AMD. Computer databases including MEDLINE (OVID), EMBASE (OVID), BIOSIS Previews (Thomson-Reuters), CINAHL (EBSCO), Health Economic Evaluations Database (HEED), ISI Web of Science (Thomson-Reuters) and the Cochrane Library (Wiley) were searched from the year 2000 to January 2015. Included papers were research studies with a sample size of 20 eyes or greater focused on AMD in adults aged 55 or older with low vision (20/60 or lower). Two independent reviewers screened and extracted relevant data from the included articles. Standardized mean difference (SMD) was chosen as an effect size to perform meta-analysis using STATA. Fixed- and random-effect models were developed based on heterogeneity. Reading Speed and Depression Scores. A total of 9 studies (885 subjects) were included. Overall, a significant improvement in reading speed was found with a SMD of 1.01 [95% CI: 0.05 to 1.97]. Low-vision rehabilitation strategies including micro-perimetric biofeedback, microscopes teaching program significantly improved reading speed. Eccentric viewing training showed the maximum improvement in reading speed. In addition, a non-significant improvement in depression scores was found with a SMD of -0.44 [95% CI: -0.96 to 0.09]. A considerable amount of research is required in the area of low-vision rehabilitation strategies for patients with AMD. Based on current research, low-vision rehabilitation aids improve reading speed. However, they do not have a significant effect on depression scores in those 55 and older with AMD.

Veterinary Medicine Needs New Green Antimicrobial Drugs

PubMed Central

Toutain, Pierre-Louis; Ferran, Aude A.; Bousquet-Melou, Alain; Pelligand, Ludovic; Lees, Peter

2016-01-01

Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in food-producing animals will increase over the coming decades; (2) the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR) of animal origin; (3) alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed “green antibiotics,” having minimal ecological impact on the animal commensal and environmental microbiomes. We first explain why animal and human commensal microbiota comprise a “turnstile” exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic, and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s). For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem. PMID:27536285

Burden of Wet Age-Related Macular Degeneration and Its Economic Implications in Singapore in the Year 2030.

PubMed

Saxena, Nakul; George, Pradeep Paul; Hoon, Heng Bee; Han, Lim Tock; Onn, Yong Shao

2016-08-01

To estimate the prevalence of wet age-related macular degeneration (AMD) in Singapore in the year 2030. This projection will help in planning appropriate care provision and build health services capacity to cater to the increasing healthcare demand in 2030. The number of AMD patients aged 40-79 years from all Singaporeans was estimated using prevalence rates from a local study and using the United Nations population projections for Singapore to 2030. Age-specific mortality was accounted for. Additionally, two main scenarios were presented: (1) Projected number of wet AMD cases if patients were not taking preventive antioxidant vitamins; (2) projected number of wet AMD cases if patients were taking preventive antioxidant vitamins. Based on these scenarios, the economic burden was calculated. The number of quality-adjusted life years (QALYs) gained as a result of improvement in visual acuity (VA) due to anti-vascular endothelial growth factor (VEGF) treatment was also calculated. An estimated growth of 42% in the number of wet AMD cases is expected by 2030. The estimated economic burden of wet AMD in 2030 for scenarios 1 and 2 is Singapore $203.1 million and $162.9 million, respectively. The QALYs gained as a result of improved VA from wet AMD treatment ranged from 10,114.4 to 14,058.8 over a 5-year period for the 2030 cohort. The burden of wet AMD is set to increase over the next 15 years. Appropriate measures to build healthcare capacity and plan for this expected surge in patients should be a priority in Singapore.

Diagnostic Sensitivity and Specificity of Dark Adaptometry for Detection of Age-Related Macular Degeneration

PubMed Central

Jackson, Gregory R.; Scott, Ingrid U.; Kim, Ivana K.; Quillen, David A.; Iannaccone, Alessandro; Edwards, John G.

2014-01-01

Purpose. Difficulty with night vision is a common complaint of patients with age-related macular degeneration (AMD). Consistent with this complaint, dark adaptation (DA) is substantially impaired in these patients. Because of the severity of the deficit, measurement of DA has been suggested as a means for the diagnosis of AMD. Previous methods for measurement of DA were time intensive (>30 minutes), which made them unsuitable for clinical use. This study evaluated a rapid DA test (≤6.5 minutes) for the detection of AMD. Methods. Dark adaptation was measured by using the AdaptDx dark adaptometer in two groups: subjects with normal retinal health and subjects with AMD. Subjects were assigned to their group by clinical examination and grading of fundus photographs. Subjects were classified as having DA consistent with normal retinal health (rod intercept ≤ 6.5 minutes) or having dark adaptation consistent with AMD (rod intercept > 6.5 minutes). Results. The eligible sample for analysis included 21 normal adults and 127 AMD patients. The rapid test was found to have a diagnostic sensitivity of 90.6% (P < 0.001) and specificity of 90.5% (P < 0.027). Thus, abnormal DA was detected in 115 of 127 AMD patients, and normal DA was found in 19 of 21 normal adults. Conclusions. The high diagnostic sensitivity and specificity compared favorably to long-duration research methods for the measurement of DA, and slit lamp biomicroscopy performed by a retina specialist. These results suggest that a rapid DA test is useful for the detection of AMD. PMID:24550363

Allyl methyl disulfide inhibits IL-8 and IP-10 secretion in intestinal epithelial cells via the NF-кB signaling pathway.

PubMed

Zhang, Yongchun; Wang, Ying; Zhang, Fang; Wang, Kaiming; Liu, Guangpu; Yang, Min; Luan, Yuxia; Zhao, Zhongxi; Zhang, Jianqiang; Cao, Xinke; Zhang, Daizhou

2015-07-01

Garlic and its active constituents have shown versatile medicinal activities in the prevention and treatment of various disorders. Allyl methyl disulfide (AMDS) was identified as one of the major bioactive components in an effective inhalation fork remedy using fresh garlic paste in our previous study. In this work, we investigated the immunological properties of AMDS to elucidate the underlying mechanisms of the fork inhalation treatment using fresh garlic. The inhibition effect of AMDS on TNF-α-induced IL-8 and IP-10 production in intestinal epithelial cell lines HT-29 and Caco-2 was first evaluated. Pretreatment of the cells with AMDS attenuated IL-8 and IP-10 secretion induced by TNF-α in a dose-dependent manner in the non-cytotoxic concentration range of 20 to 150 μM. Mechanistic studies revealed that AMDS suppressed the accumulation of IL-8 mRNA and inhibited IкBα degradation and NF-кB p65 translocation into the nucleus at both the transcriptional and translational levels, suggesting that the attenuation effort of AMDS on cytokine IL-8 secretion might at least be partially related to the NF-κB signaling pathway. These results suggest that AMDS may be a promising phytochemical agent in the treatment of immunological disorders, such as ulcerative colitis, Crohn's disease, intestinal inflammatory diseases and others. In addition, the mechanistic study data indicated that immune modulation could be one of the therapeutic mechanisms of the effective fork treatment containing AMDS as one of the major components. Copyright © 2015 Elsevier B.V. All rights reserved.

Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

PubMed Central

Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

2014-01-01

Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

Age-related macular degeneration.

PubMed

Cheung, Lily K; Eaton, Angie

2013-08-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

Subretinal Pigment Epithelial Deposition of Drusen Components Including Hydroxyapatite in a Primary Cell Culture Model

DOE PAGES

Pilgrim, Matthew G.; Lengyel, Imre; Lanzirotti, Antonio; ...

2017-02-01

Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components. Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry. Apparently functional primary RPE cells, when cultured on 10-lm-thickmore » inserts with 0.4-lm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks. In conclusion, the data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch’s membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss.« less

Subretinal Pigment Epithelial Deposition of Drusen Components Including Hydroxyapatite in a Primary Cell Culture Model.

PubMed

Pilgrim, Matthew G; Lengyel, Imre; Lanzirotti, Antonio; Newville, Matt; Fearn, Sarah; Emri, Eszter; Knowles, Jonathan C; Messinger, Jeffrey D; Read, Russell W; Guidry, Clyde; Curcio, Christine A

2017-02-01

Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch's membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components. Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry. Apparently functional primary RPE cells, when cultured on 10-μm-thick inserts with 0.4-μm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks. The data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch's membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss.

Subretinal Pigment Epithelial Deposition of Drusen Components Including Hydroxyapatite in a Primary Cell Culture Model

PubMed Central

Pilgrim, Matthew G.; Lengyel, Imre; Lanzirotti, Antonio; Newville, Matt; Fearn, Sarah; Emri, Eszter; Knowles, Jonathan C.; Messinger, Jeffrey D.; Read, Russell W.; Guidry, Clyde; Curcio, Christine A.

2017-01-01

Purpose Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch's membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components. Methods Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry. Results Apparently functional primary RPE cells, when cultured on 10-μm-thick inserts with 0.4-μm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks. Conclusions The data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch's membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss. PMID:28146236

Subretinal Pigment Epithelial Deposition of Drusen Components Including Hydroxyapatite in a Primary Cell Culture Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilgrim, Matthew G.; Lengyel, Imre; Lanzirotti, Antonio

Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components. Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry. Apparently functional primary RPE cells, when cultured on 10-lm-thickmore » inserts with 0.4-lm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks. In conclusion, the data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch’s membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss.« less

Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

2012-01-01

Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

PubMed

Adamus, Grazyna

2017-03-01

Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease, there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood is necessary. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.

PubMed

Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A; Khan, Shafiq A; Chaney, William G; Bu, Xiu R; Lin, Ming-Fong

2014-10-10

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells

PubMed Central

Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A.; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A.; Khan, Shafiq A.; Chaney, William G.; Bu, Xiu R.; Lin, Ming-Fong

2014-01-01

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. PMID:25050738

Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images

PubMed Central

Phan, Thanh Vân; Seoud, Lama; Chakor, Hadi; Cheriet, Farida

2016-01-01

Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features' relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality. PMID:27190636

Intraocular lenses in age-related macular degeneration.

PubMed

Grzybowski, Andrzej; Wasinska-Borowiec, Weronika; Alio, Jorge L; Amat-Peral, Pedro; Tabernero, Juan

2017-09-01

The aim of this work is to review the lenses, assessing their advantages and disadvantages. We describe a total of seven types of intraocular lenses (IOLs) recommended for age-related macular degeneration (AMD). We used the PubMed web platform to search for implantable devices in various stages of AMD. We searched for both prospective and retrospective studies and also case reports. Clinical results in AMD patients have been described for a total of seven types of IOLs recommended for AMD: an implantable miniature telescope (IMT), IOL-VIP System, Lipshitz macular implant (LMI), sulcus-implanted Lipshitz macular implant, LMI-SI, Fresnel Prism Intraocular Lens, iolAMD and Scharioth Macula Lens. We conclude that to objectively ascertain the effectiveness and safety of these lenses, further independent clinical studies with longer follow-up data are necessary prior to the general use of these optical devices.

Advances in Age-related Macular Degeneration Understanding and Therapy

PubMed Central

Miller, Joan W; Bagheri, Saghar; Vavvas, Demetrios G

2017-01-01

While the development of anti-vascular endothelial growth factor (anti-VEGF) as a therapy for neovascular age-related macular degeneration (AMD) was a great success, the pathologic processes underlying dry AMD that eventually leads to photoreceptor dysfunction, death, and vision loss remain elusive to date, with a lack of effective therapies and increasing prevalence of the disease. There is an overwhelming need to improve the classification system of AMD, to increase our understanding of cell death mechanisms involved in both neovascular and non-neovascular AMD, and to develop better biomarkers and clinical endpoints to eventually be able to identify better therapeutic targets—especially early in the disease process. There is no doubt that it is a matter of time before progress will be made and better therapies will be developed for non-neovascular AMD. PMID:29142592

Hypomethylation of IL17RC Promoter Associates with Age-related Macular Degeneration

PubMed Central

Wei, Lai; Liu, Baoying; Tuo, Jingsheng; Shen, Defen; Chen, Ping; Li, Zhiyu; Liu, Xunxian; Ni, Jia; Dagur, Pradeep; Sen, H. Nida; Jawad, Shayma; Ling, Diamond; Park, Stanley; Chakrabarty, Sagarika; Meyerle, Catherine; Agron, Elvira; Ferris, Frederick L.; Chew, Emily Y.; McCoy, J. Philip; Blum, Emily; Francis, Peter J.; Klein, Michael L.; Guymer, Robyn H.; Baird, Paul N.; Chan, Chi-Chao; Nussenblatt, Robert B.

2012-01-01

SUMMARY Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its etiology. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis. PMID:23177625

Comparing humans and deep learning performance for grading AMD: A study in using universal deep features and transfer learning for automated AMD analysis.

PubMed

Burlina, Philippe; Pacheco, Katia D; Joshi, Neil; Freund, David E; Bressler, Neil M

2017-03-01

When left untreated, age-related macular degeneration (AMD) is the leading cause of vision loss in people over fifty in the US. Currently it is estimated that about eight million US individuals have the intermediate stage of AMD that is often asymptomatic with regard to visual deficit. These individuals are at high risk for progressing to the advanced stage where the often treatable choroidal neovascular form of AMD can occur. Careful monitoring to detect the onset and prompt treatment of the neovascular form as well as dietary supplementation can reduce the risk of vision loss from AMD, therefore, preferred practice patterns recommend identifying individuals with the intermediate stage in a timely manner. Past automated retinal image analysis (ARIA) methods applied on fundus imagery have relied on engineered and hand-designed visual features. We instead detail the novel application of a machine learning approach using deep learning for the problem of ARIA and AMD analysis. We use transfer learning and universal features derived from deep convolutional neural networks (DCNN). We address clinically relevant 4-class, 3-class, and 2-class AMD severity classification problems. Using 5664 color fundus images from the NIH AREDS dataset and DCNN universal features, we obtain values for accuracy for the (4-, 3-, 2-) class classification problem of (79.4%, 81.5%, 93.4%) for machine vs. (75.8%, 85.0%, 95.2%) for physician grading. This study demonstrates the efficacy of machine grading based on deep universal features/transfer learning when applied to ARIA and is a promising step in providing a pre-screener to identify individuals with intermediate AMD and also as a tool that can facilitate identifying such individuals for clinical studies aimed at developing improved therapies. It also demonstrates comparable performance between computer and physician grading. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of macular pigment optical density in patients with dry and wet age-related macular degeneration.

PubMed

Ozyurt, Ayhan; Kocak, Nilufer; Akan, Pınar; Calan, Ozlem Gursoy; Ozturk, Taylan; Kaya, Mahmut; Karahan, Eyup; Kaynak, Suleyman

2017-06-01

The aim of the study was to evaluate the macular pigment optical density (MPOD) levels in patients with wet age-related macular degeneration (AMD), dry AMD, and also in healthy controls. This study was conducted at Department of Ophthalmology, and the study design was a prospective study. Forty-eight patients with wet AMD, 51 patients with dry AMD, and 50 controls were included in the study. All patients were naive to both previous lutein or zeaxanthin administration and any previous intravitreal injections. Fundus reflectance (VISUCAM 500, reflectance of a single 460 nm wavelength) was used to measure the MPOD levels. Three groups were compared regarding age, gender, serum lutein, and zeaxanthin concentrations as well as MPOD levels. Serum lutein and zeaxanthin levels were significantly higher in control group when compared with wet AMD (Group 1) and dry AMD (Group 2) (P = 0.001 and P< 0.001, respectively). Mean MPOD was found to be similar in all of the three study subgroups (P = 0.630). However, maximum MPOD was significantly higher in control group when compared with Group 1 and 2 (P = 0.003). There was no correlation between serum lutein or zeaxanthin concentrations and mean MPOD levels (P = 0.815, r = 0.014 and P = 0.461, r = 0.043, respectively), but there was a weak correlation between serum zeaxanthin concentration and maximum MPOD level (P = 0.042, r = 0.124). Maximum MPOD level was found to be correlated with the level of AMD (Group 1, 2, and 3; r = 0.184, P = 0.041). Maximum MPOD level was found to be lower in patients with AMD when compared with control cases. Mean MPOD and maximum MPOD levels were similar in wet and dry AMD Groups. These results can be applied clinically keeping in mind that MPOD measurements with one wavelength reflectometry may not be completely reliable.

Smoking, Dietary Betaine, Methionine, and Vitamin D in Monozygotic Twins with Discordant Macular Degeneration: Epigenetic Implications

PubMed Central

Seddon, Johanna M.; Reynolds, Robyn; Shah, Heeral R.; Rosner, Bernard

2012-01-01

Objective We evaluated monozygotic twin pairs with discordant age-related macular degeneration (AMD) phenotypes to assess differences in behavioral and nutritional factors. Design Case series. Participants Caucasian male twin pairs from the United States Twin Study of Macular Degeneration. Methods Twin pairs were genotyped to confirm monozygosity. Ocular characteristics were evaluated based on fundus photographs using the Wisconsin Grading System and a 5-grade Clinical Age-Related Maculopathy Staging System. We selected twin pairs discordant in each of the following phenotypic categories: Stage of AMD (n = 28), drusen area (n = 60), drusen size (n = 40), and increased pigment area (n = 56). The Wilcoxon signed-rank test and linear regression were used to assess associations between behavioral and nutritional characteristics and each phenotype within discordant twin pairs. Main Outcome Measures Differences in smoking and dietary factors within twin pairs discordant for stage of AMD, drusen area, drusen size, and pigment area. Results Representative fundus photographs depict the discordant phenotypes. Pack-years of smoking were higher for the twin with the more advanced stage of AMD (P = 0.05). Higher dietary intake of vitamin D was present in the twins with less severe AMD (P = 0.01) and smaller drusen size (P = 0.05) compared with co-twins, adjusted for smoking and age. Dietary intakes of betaine and methionine were significantly higher in the twin with lower stage of AMD (P = 0.009) and smaller drusen area (P = 0.03), respectively. Conclusions The twin with the more advanced stage of AMD, larger drusen area, drusen size, and pigment area tended to be the heavier smoker. The twin with the earlier stage of AMD, smaller drusen size and area, and less pigment tended to have higher dietary vitamin D, betaine, or methionine intake. Results suggest that behavioral and nutritional factors associated with epigenetic mechanisms are involved in the etiology of AMD, in addition to genetic susceptibility. PMID:21620475

Clinical characteristics of reticular pseudodrusen in Korean patients.

PubMed

Lee, Mee Yon; Yoon, Jaemoon; Ham, Don-Il

2012-03-01

To clarify the clinical characteristics of reticular pseudodrusen in Korean patients. Retrospective, observational, consecutive case series. A total of 255 eyes of 130 patients diagnosed with reticular pseudodrusen were evaluated. Reticular pseudodrusen were diagnosed by characteristic fundus findings using ophthalmoscopy, color fundus photography with blue-channel examination, near-infrared photography, red-free photography, autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography. Age-related macular degeneration (AMD) was determined by the International Classification and Grading System. The mean age was 72.6 ± 9.0 years (range, 43 to 92 years). Most reticular pseudodrusen patients had bilateral disease (97.7%), with a female preponderance (86.2%). All 3 patients who showed unilateral reticular pseudodrusen had neovascular AMD in the eye with no reticular pseudodrusen. AMD was found in 183 eyes (71.8 %), among which early AMD was found in 115 eyes (45.1%), geographic atrophy was found in 41 eyes (16.1%), and neovascular AMD was found in 27 eyes (10.6%). The mean age of patients with AMD and with no AMD was 73.7 ± 9.2 years (range, 58 to 92 years) and 69.9 ± 11.7 years (range, 43 to 90 years), respectively, and there was a statistical difference between these 2 groups (P < .05). Classic choroidal neovascularization was found in 13 eyes (48.1%), and occult choroidal neovascularization was found in 14 eyes (51.9%) in the neovascular AMD group. Reticular pseudodrusen occurs in Koreans, and clinical manifestations of reticular pseudodrusen in Koreans did not differ significantly from those described in white persons. However, our study demonstrated a higher rate of bilaterality compared with those previously reported, and geographic atrophy was found to be associated more commonly with reticular pseudodrusen than with neovascular AMD. Ethnical differences may be associated with these findings, and further studies are required. Copyright © 2012 Elsevier Inc. All rights reserved.

Increase in peripheral blood mononuclear cell Toll-like receptor 2/3 expression and reactivity to their ligands in a cohort of patients with wet age-related macular degeneration

PubMed Central

Zhu, Yi; Liang, Liang; Qian, Dan; Yu, Hongsong; Yang, Peizeng; Lei, Bo

2013-01-01

Purpose To investigate Toll-like receptor (TLR) expression and reactivity in patients with the wet form age-related macular degeneration (AMD). Methods Blood samples were collected from 25 patients with wet AMD and 25 age-matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated with Ficoll-Hypaque density gradient centrifugation. Expression of TLR1 to TLR10 mRNAs in PBMCs from 15 patients with wet AMD and 15 controls was assessed with real-time PCR. TLR2 and TLR3 protein levels in PBMCs from six patients with wet AMD and six controls were measured with flow cytometry. After PBMCs were stimulated with peptidoglycan (PGN) and poly(I:C), the specific ligands of TLR2 and TLR3, cytokines interleukin-6 (IL-6), IL-8, VEGF, and monocyte chemoattractant protein-1 (MCP-1) production in 11 patients with wet AMD and 11 controls were assessed. Results TLR2 and TLR3 mRNA and protein expression in the PBMCs of the patients with wet AMD was significantly higher than that in the controls. However, the difference in TLR1 and TLR4–10 mRNA expression between the two groups was not significant. The PBMCs of the patients with wet AMD produced more IL-6 and IL-8 proteins than the controls in response to PGN, a ligand for TLR2, and more IL-6 protein than the controls in response to poly(I:C), the ligand for TLR3. However, there was no significant difference in vascular endothelial growth factor and monocyte chemoattractant protein-1 production between the wet AMD group and the control group when the PBMCs were stimulated with PGN or poly(I:C). Conclusions Our data suggested that upregulation of TLR2 and TLR3 may be associated with the pathogenesis of wet AMD. PMID:23946637

Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

PubMed Central

GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

2014-01-01

Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan. PMID:17101537

Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2.

PubMed

Cachulo, Maria da Luz; Laíns, Inês; Lobo, Conceição; Figueira, João; Ribeiro, Luísa; Marques, João P; Costa, José; Vieira, António; Rodrigues, João; Alves, Dalila; Nunes, Sandrina; Costa, Miguel; Rodrigues, Victor; Cunha-Vaz, José; Delcourt, Cecile; Silva, Rufino

2016-09-01

To determine the age- and sex-specific prevalence of early and late age-related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. A population of 6023 adults aged ≥55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Prevalence of age-related macular degeneration in a large European cohort: results from the population-based Gutenberg Health Study.

PubMed

Korb, Christina A; Kottler, Ulrike B; Wolfram, Christian; Hoehn, René; Schulz, Andreas; Zwiener, Isabella; Wild, Philipp S; Pfeiffer, Norbert; Mirshahi, Alireza

2014-09-01

The aim of this study was to describe the sex- and age-specific prevalence of age-related macular degeneration (AMD) and its correlation with urban or rural residence in a large and relatively young European cohort. We evaluated fundus photographs from participants in the Gutenberg Health Study (GHS), a population-based, prospective, observational, single-centre study in the Rhineland-Palatine region in midwestern Germany. The participants were 35-74 years of age at enrolment. The fundus images were classified as described in the Rotterdam Study and were graded independently by two experienced ophthalmologists (CK and UBK) based on the presence of hard and soft drusen, retinal pigmentary abnormalities, and signs of atrophic or neovascular age-related macular generation (AMD). Photographs from 4,340 participants were available for grading. Small, hard drusen (<63 μm, stages 0b and 0c) were present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6% [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9-3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1-0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age group. In all age groups, signs of early AMD were detected in 11.9% of individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0% [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage 4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence (rural vs. urban) were not associated with different rates of AMD. In this study, the prevalence of AMD increased dramatically with age; however, although AMD is usually thought to occur after age 50, signs of early AMD were found in 3.8% of individuals in the youngest age group (younger than 45 years). This population-based sample is the first to provide substantial epidemiologic data from a large German cohort, including data on macular degeneration in younger age groups and incidence data after recall.

DNA Sequence Variants in PPARGC1A, a Gene Encoding a Coactivator of the ω-3 LCPUFA Sensing PPAR-RXR Transcription Complex, Are Associated with NV AMD and AMD-Associated Loci in Genes of Complement and VEGF Signaling Pathways

PubMed Central

SanGiovanni, John Paul; Chen, Jing; Sapieha, Przemyslaw; Aderman, Christopher M.; Stahl, Andreas; Clemons, Traci E.; Chew, Emily Y.; Smith, Lois E. H.

2013-01-01

Background Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and use of peroxisome proliferator activator receptor (PPAR)-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG) co-activator 1 alpha (PPARGC1A), a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR) transcription complex, may influence neovascularization (NV) in age-related macular degeneration (AMD). Methods We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A. Results A DNA coding variant (rs3736265) and a 3'UTR-resident regulatory variant (rs3774923) in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs). SNP-SNP interactions existed for NV AMD (P<0.005) with rs3736265 and a AMD-associated variant in complement factor B (CFB, rs512559). PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P≤0.003) of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033), a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678) showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P≤0.003). C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice – these animals also showed 70% reduction in retinal NV (P≤0.001). Conclusion Ligands and co-activators of the ω-3 LCPUFA sensing PPAR-RXR axis may influence retinal angiogenesis in NV AMD via the complement and VEGF signaling systems. We have linked the co-activator of a lipid-sensing transcription factor (PPARG co-activator 1 alpha, PPARGC1A) to age-related macular degeneration (AMD) and AMD-associated genes. PMID:23335958

Reticular pseudodrusen in age-related macular degeneration.

PubMed

Hogg, Ruth Esther

2014-08-01

Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.

Association between CFH Y402H Polymorphism and Age Related Macular Degeneration in North Indian Cohort

PubMed Central

Gupta, Amod; Prabhakar, Sudesh; Singh, Ramandeep; Sharma, Suresh Kumar; Chen, Wei

2013-01-01

The purpose of the study was to determine serum complement factor H (CFH) levels in patients of age related macular degeneration (AMD) and examine its association with CFH Y402H polymorphism. 115 AMD patients and 61 normal controls were recruited in this study. The single nucleotide polymorphism was assayed by real time PCR and serum CFH levels were measured by ELISA and standardized to total serum protein. Chi-square test was applied to polymorphism analysis while Mann Whitney U-statistic for CFH-levels. Mendelian randomization approach was used for determining causal relationship. The genotype frequency differed between the AMD patients (TT- 18.3%, TC-41.3% and CC-40.4%) and controls (TT-76.3%, TC-13.6%, and CC-10.1%) (p = 0001). The frequency of alleles was also significantly different when AMD (T-39% and C-61%) was compared to controls (T-83% and C-17%) (p = 0.0001). Level of serum CFH was significantly lower in AMD patients as compared to normal controls (p = 0.001). Our data showed that the CFH Y402H polymorphism is a risk factor for AMD in the North Indian population. Mendelian randomization approach revealed that CFH Y402H polymorphism affects AMD risk through the modification of CFH serum levels. PMID:23922956

Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments.

PubMed

Rein, David B; Wittenborn, John S; Zhang, Xinzhi; Honeycutt, Amanda A; Lesesne, Sarah B; Saaddine, Jinan

2009-04-01

To forecast age-related macular degeneration (AMD) and its consequences in the United States through the year 2050 with different treatment scenarios. We simulated cases of early AMD, choroidal neovascularization (CNV), geographic atrophy (GA), and AMD-attributable visual impairment and blindness with 5 universal treatment scenarios: (1) no treatment; (2) focal laser and photodynamic therapy (PDT) for CNV; (3) vitamin prophylaxis at early-AMD incidence with focal laser/PDT for CNV; (4) no vitamin prophylaxis followed by focal laser treatment for extra and juxtafoveal CNV and anti-vascular endothelial growth factor treatment; and (5) vitamin prophylaxis at early-AMD incidence followed by CNV treatment, as in scenario 4. Cases of early AMD increased from 9.1 million in 2010 to 17.8 million in 2050 across all scenarios. In non-vitamin-receiving scenarios, cases of CNV and GA increased from 1.7 million in 2010 to 3.8 million in 2050 (25% lower in vitamin-receiving scenarios). Cases of visual impairment and blindness increased from 620 000 in 2010 to 1.6 million in 2050 when given no treatment and were 2.4%, 22.0%, 16.9%, and 34.5% lower in scenarios 2, 3, 4, and 5, respectively. Prevalence of AMD will increase substantially by 2050, but the use of new therapies can mitigate its effects.

Smoking, antioxidant supplementation and dietary intakes among older adults with age-related macular degeneration over 10 years.

PubMed

Gopinath, Bamini; Flood, Victoria M; Kifley, Annette; Liew, Gerald; Mitchell, Paul

2015-01-01

We aimed to compare the micronutrient usage and other lifestyle behaviors over 10 years among those with and without age-related macular degeneration (AMD). 1612 participants aged 49+ years at baseline were re-examined over 10 years, west of Sydney, Australia. AMD was assessed from retinal photographs. Dietary data were collected using a semi-quantitative food frequency questionnaire. Smoking status was self-reported. 56 participants had any AMD at baseline, of these 25% quit smoking at 5 years and were still not smoking at 10-year follow-up. Among participants who had below the recommended intake of vitamins A, C or E supplements at baseline, those who did compared to those who did not develop late AMD over 10 years were more likely to report vitamins A (total), C or E supplement intake above the recommended intake at 10-year follow-up: multivariable-adjusted OR 4.21 (95% CI 1.65-10.73); OR 6.52 (95% CI 2.76-15.41); and OR 5.71 (95% CI 2.42-13.51), respectively. Participants with compared to without AMD did not appreciably increase fish, fruit and vegetable consumption and overall diet quality. Adherence to smoking and dietary recommendations was poor among older adults with AMD. However, uptake of antioxidant supplements increased significantly among those with late AMD.

Diversity of the Sediment Microbial Community in the Aha Watershed (Southwest China) in Response to Acid Mine Drainage Pollution Gradients.

PubMed

Sun, Weimin; Xiao, Tangfu; Sun, Min; Dong, Yiran; Ning, Zengping; Xiao, Enzong; Tang, Song; Li, Jiwei

2015-08-01

Located in southwest China, the Aha watershed is continually contaminated by acid mine drainage (AMD) produced from upstream abandoned coal mines. The watershed is fed by creeks with elevated concentrations of aqueous Fe (total Fe > 1 g/liter) and SO4 (2-) (>6 g/liter). AMD contamination gradually decreases throughout downstream rivers and reservoirs, creating an AMD pollution gradient which has led to a suite of biogeochemical processes along the watershed. In this study, sediment samples were collected along the AMD pollution sites for geochemical and microbial community analyses. High-throughput sequencing found various bacteria associated with microbial Fe and S cycling within the watershed and AMD-impacted creek. A large proportion of Fe- and S-metabolizing bacteria were detected in this watershed. The dominant Fe- and S-metabolizing bacteria were identified as microorganisms belonging to the genera Metallibacterium, Aciditerrimonas, Halomonas, Shewanella, Ferrovum, Alicyclobacillus, and Syntrophobacter. Among them, Halomonas, Aciditerrimonas, Metallibacterium, and Shewanella have previously only rarely been detected in AMD-contaminated environments. In addition, the microbial community structures changed along the watershed with different magnitudes of AMD pollution. Moreover, the canonical correspondence analysis suggested that temperature, pH, total Fe, sulfate, and redox potentials (Eh) were significant factors that structured the microbial community compositions along the Aha watershed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Soft Tissue Changes in Cleft Lip and Palate Patients: Anterior Maxillary Distraction versus Conventional Le-Fort I Osteotomy.

PubMed

Markose, Eldho; Paulose, Joby; Paul, Eldho T

2013-12-01

The purpose of the study was to compare the soft tissue changes after maxillary advancement in patients with maxillary deficiency associated with cleft lip and palate (CLP) by two approaches-anterior maxillary distraction (AMD) and advancement LeFort I osteotomy (ALO). Twenty patients with maxillary hypoplasia associated with cleft lip and palate who had undergone either LeFort I osteotomy or distraction osteogenesis with maxillary advancement were included in this study. Lateral cephalogram taken at various intervals of time were used to evaluate soft tissue and hard tissue changes over time. In both groups, vertical as well as horizontal changes in pronasale was well observed. A substantial increase in nasal parameters was noted in case of AMD group in comparison to ALO. Though maxillary advancement was evident in both the groups, a significant and consistent change was observed in AMD. Significant vertical and horizontal changes were seen with respect to subnasale and labrale superius in AMD group. Soft tissue as well as hard tissue relapse was greater in ALO group than AMD group. Significant soft tissue and hard tissue changes were clearly observed in both the groups, but the treatment results were more consistent in cases treated with AMD. Hence AMD could be considered as a better treatment of choice in cases of maxillary hypoplasia associated with cleft lip and palate.

Effects of Age-Related Macular Degeneration on Postural Sway

PubMed Central

Chatard, Hortense; Tepenier, Laure; Jankowski, Olivier; Aussems, Antoine; Allieta, Alain; Beydoun, Talal; Salah, Sawsen; Bucci, Maria P.

2017-01-01

Purpose: To compare the impact of unilateral vs. bilateral age-related macular degeneration (AMD) on postural sway, and the influence of different visual conditions. The hypothesis of our study was that the impact of AMD will be different between unilateral and bilateral AMD subjects compared to age-matched healthy elderly. Methods: Postural stability was measured with a platform (TechnoConcept®) in 10 elderly unilateral AMD subjects (mean age: 71.1 ± 4.6 years), 10 elderly bilateral AMD subjects (mean age: 70.8 ± 6.1 years), and 10 healthy age-matched control subjects (mean age: 69.8 ± 6.3 years). Four visual conditions were tested: both eyes viewing condition (BEV), dominant eye viewing (DEV), non-dominant eye viewing (NDEV), and eyes closed (EC). We analyzed the surface area, the length, the mean speed, the anteroposterior (AP), and mediolateral (ML) displacement of the center of pressure (CoP). Results: Bilateral AMD subjects had a surface area (p < 0.05) and AP displacement of the CoP (p < 0.01) higher than healthy elderly. Unilateral AMD subjects had more AP displacement of the CoP (p < 0.05) than healthy elderly. Conclusions: We suggest that ADM subjects could have poor postural adaptive mechanisms leading to increase their postural instability. Further studies will aim to improve knowledge on such issue and to develop reeducation techniques in these patients. PMID:28408876

T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PubMed

Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

2017-11-20

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

The Revival of a Failed Constructed Wetland Treating of a High Fe Load AMD

Treesearch

A.D. Karathanasis; C.D. Barton

1999-01-01

Acid mine drainage (AMD) from abandoned mines has significantly impaired water quality in eastern Kentucky. A small surface flow wetland constructed in 1989 to reduce AMD effects and subsequently failed after six months of operation was renovated by incorporating anoxic limestone drains (ALDs) and anaerobic subsurface drains promoting vertical flow through successive...

Spatial Variations In The Fate And Transport Of Metals In A Mining-Influenced Stream, North Fork Clear Creek, Colorado

EPA Science Inventory

North Fork Clear Creek (NFCC) receives acid-mine drainage (AMD) from multiple abandoned mines in the Clear Creek Watershed. Point sources of AMD originate In the Black Hawk/Central City region of the stream. Water chemistry also is influenced by several non-point sources of AMD,...

The national and subnational prevalence and burden of age–related macular degeneration in China

PubMed Central

Song, Peige; Du, Yuhang; Chan, Kit Yee; Theodoratou, Evropi; Rudan, Igor

2017-01-01

Background Age–related macular degeneration (AMD) is the third most common cause of blindness, and the fourth leading cause of visual impairment worldwide, but little is known about the burden of this disease in the most populous country–China. This study provides the first comprehensive estimates of the prevalence and burden of AMD in China from 1990 to 2015, with projections till 2050. Methods In this study, a systematic review and meta–analysis was conducted to estimate the prevalence of AMD in China. China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM–SinoMed), PubMed, Embase and Medline were searched before September 2016. Multilevel mixed–effect meta–regression was performed to define the prevalence rates of AMD and its subtypes. UN population data were used to estimate and project the number of people affected from 1990 to 2050. Based on different demographic and geographic features, the national burden of AMD in 2000 and 2010 was distributed to different regions in China. Results Our search returned 2016 citations, of which 25 met the inclusion criteria. The prevalence of any AMD ranged from 2.44% (95% CI = 1.85–3.22) in people aged 45–49 years to 18.98% (95% CI = 15.05–23.66) in people aged 85–89 years. Prevalence of early AMD ranged from 1.79% (95% CI = 1.05–3.02) to 10.05% (95% CI = 6.17–15.97), and, in the case of late AMD, from 0.38% (95% CI = 0.16–0.97) to 3.88% (95% CI = 1.68–9.13). In late AMD, the prevalence of geographic atrophy (GA) was 0.15% (95% CI = 0.05–0.47) in people aged 45–49 years and 1.09% (95% CI = 0.35–3.36) in those aged 85–89 years, and the prevalence of neovascular AMD (NVAMD) ranged between 0.24% (95% CI = 0.11–0.50) and 2.79% (95% CI = 1.33–5.77). The number of people with any AMD was 12.01 million (95% CI = 9.29–15.46) in 1990 and 26.65 million (95% CI = 20.62–34.27) in 2015. Within the same period, the number of people with early AMD increased from 9.44 million (95% CI = 7.74–11.15) to 20.91 million (95% CI = 17.16–24.68), and those with late AMD rose from 2.58 million (95% CI = 1.56–4.30) to 5.74 million (95% CI = 3.46–9.59). In late AMD, the number of people living with GA ranged from 0.87 million (95% CI = 0.40–1.83) in 1990 to 1.93 million (95% CI = 0.89–4.08) in 2015, and NVAMD from 1.71 million (95% CI = 1.16–2.47) to 3.81 million (95% CI = 2.57–5.51). The projected number of people with any AMD in 2020 is 31.23 million (95% CI = 24.18–40.14), increasing to 55.19 million (95% CI = 43.04–70.30) in 2050. Between different regions, the South Central owed the most AMD cases (5.50 million in 2000 and 7.52 million in 2010), whereas the North–West China the least (0.66 million in 2000 and 0.95 million in 2010). Conclusions The estimates in this study suggest a substantial burden of AMD in China, with the ageing process in Chinese society, this burden will be increasing in the foreseen future. Primary and secondary prevention and treatment and effective government response are urgently needed. Improved epidemiological studies are also required to better develop eye–care strategies and health services. PMID:29302323

Injection of coal combustion byproducts into the Omega Mine for the reduction of acid mine drainage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gray, T.A.; Moran, T.C.; Broschart, D.W.

1998-12-31

The Omega Mine Complex is located outside of Morgantown, West Virginia. The mine is in the Upper Freeport Coal, an acid-producing coal seam. The coal was mined in a manner that has resulted in acid mine drainage (AMD) discharges at multiple points. During the 1990`s, the West Virginia Division of Environmental Protection (WVDEP) assumed responsibility for operating a collection and treatment system for the AMD. Collection and treatment costs are approximately $300,000 per year. An innovative procedure of injecting grout into the mine workings to reduce AMD and the resulting treatment costs is proposed. The procedure involves injecting grout mixesmore » composed primarily of coal combustion byproducts (CCB`s) and water, with a small quantity of cement. The intention of the injection program is to fill the mine voids in the north lobe of the Omega Mine (an area where most of the acidity is believed to be generated) with the grout, thus reducing the contact of air and water with potentially acidic material. The grout mix design consists of an approximate 1:1 ratio of fly ash to byproducts from fluidized bed combustion. Approximately 100 gallons of water per cubic yard of grout is used to help achieve flowability. Observation of the mine workings via subsurface borings and downhole video camera operation confirmed that first-mined areas were generally open while second-mined areas were generally partially collapsed. Closer injection hole spacing was used in second-mined areas to account for collapsed workings. The construction documents have been prepared with the project being bid in late 1997. The engineer`s cost estimate was approximately $2,500,000, with the low bid of approximately $2,300,000 being submitted by Howard Concrete Pumping of Bridgeville, PA.« less

Inflammation, Complement Factor H, and Age-Related Macular Degeneration: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Klein, Ronald; Knudtson, Michael D.; Klein, Barbara E. K.; Wong, Tien Y.; Cotch, Mary Frances; Liu, Kiang; Cheng, Ching Y.; Burke, Gregory L.; Saad, Mohammed F.; Jacobs, David R.; Sharrett, A. Richey

2010-01-01

Objective To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T→C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese. Design Population-based, cross-sectional study. Participants We included 5887 persons aged 45 to 84 years with gradable AMD. Methods Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained. Main Outcome Measure Prevalence of AMD. Results While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33–4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21–3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95% CI, 1.14–2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95% CI, 1.06–1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95% CI, 1.14–3.97) and soft distinct drusen (OR, 1.76; 95% CI, 1.00–3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95% CI, 1.10–2.04), soft indistinct drusen (OR, 1.84; 95% CI, 1.09–3.10), and large drusen area (OR, 1.66; 95% CI, 1.02–2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks. Conclusions This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups. PMID:18538409

ASSOCIATION BETWEEN THE VITREOMACULAR INTERFACE AND OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS IN WET AGE-RELATED MACULAR DEGENERATION.

PubMed

Ashraf, Mohammed; Souka, Ahmed; Adelman, Ron A

2017-09-01

To study the effect of the vitreomacular interface on various wet age-related macular degeneration (AMD) characteristics including the size and type of choroidal neovascularization (CNV), choroidal thickness, and activity of the CNV. This was a retrospective observational cross-sectional study. The study included 43 patients (51 eyes) with treatment-naive age-related macular degeneration. Twenty-six patients with wet AMD in one eye and dry AMD in the other eye were included in a paired-eye analysis. Patients underwent optical coherence tomography examination using Heidelberg Spectralis (spectral domain optical coherence tomography) at presentation to determine the type of CNV and the vitreomacular status. In addition, various parameters were measured including the choroidal thickness and horizontal width and vertical height measurements of the CNV. There was no correlation between the height, width, activity or type of the CNV, and the presence or absence of vitreomacular adhesion. The mean choroidal thickness (using enhanced depth imaging) in cases with vitreomacular adhesion was 272.57 μm compared with 197.32 μm in cases with no vitreomacular adhesion, a statistically significant difference (P = 0.003). In the paired-eye study (21 patients), there was no significant difference between the eyes with wet AMD and dry AMD with regard to vitreomacular status or the choroidal thickness. In a subgroup analysis, patients with Type 1 CNV had a significantly higher percentage of vitreomacular adhesion compared with the other eye with dry AMD (P = 0.034). In conclusion, the vitreomacular interface does seem to be associated with an increased choroidal thickness in cases of wet AMD. Furthermore, the association between the vitreomacular interface and wet AMD is more significant for Type 1 CNV.

Complement factor H polymorphisms in Japanese population with age-related macular degeneration.

PubMed

Okamoto, Haru; Umeda, Shinsuke; Obazawa, Minoru; Minami, Masayoshi; Noda, Toru; Mizota, Atsushi; Honda, Miki; Tanaka, Minoru; Koyama, Risa; Takagi, Ikue; Sakamoto, Yoshihiro; Saito, Yoshihiro; Miyake, Yozo; Iwata, Takeshi

2006-03-06

To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD). Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 age-matched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results. Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified. The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective.

Population-based age group specific annual incidence rates of symptomatic age-related macular degeneration.

PubMed

Saari, Jukka M

2014-01-01

To study the population-based annual incidence rates of exudative, dry and all cases of symptomatic age-related macular degeneration (AMD) in different age and sex groups. This is a one year, prospective, population-based study on all consecutive new patients with AMD in the hospital district of Central Finland. The diagnosis was confirmed in all patients with slit lamp biomicroscopy, optical coherence tomography (OCT) using a Spectralis HRA + OCT device, and the Heidelberg Eye Explorer 1.6.2.0 program. Fluorescein angiograms were taken when needed. The population-based annual incidence rates of all cases of symptomatic AMD increased from 0.03% (95% CI, 0.01-0.05%) in the age group 50-59 years to 0.82% (95% CI, 0.55-1.09%) in the age group 85-89 years and were 0.2% (95% CI, 0.17-0.24%) in exudative, 0.11% (95% CI, 0.09-0.14%) in dry, and 0.32% (95% CI, 0.28-0.36%) in all cases of AMD in the age group 60 years and older. During the next 20 years in Central Finland the population-based annual incidence rates can be estimated to increase to 0.27% (95% CI, 0.24-0.30%) in exudative, to 0.13% (95% CI, 0.11-0.15%) in dry, and to 0.41% (95% CI, 0.37-0.45%) in all cases of AMD in the age group 60 years and older. The population-based annual incidence of AMD did not show statistically significant differences between males and females (p>0.1). The population-based age-group specific annual incidence rates of symptomatic AMD of this study may help to plan health care provision for patients of AMD.

A follow-up survey on the knowledge of age-related macular degeneration and its risk factors among Singapore residents after 5 years of nation-wide awareness campaigns.

PubMed

Sanjay, Srinivasan; Chin, You Chuen; Teo, Hui Ting; Ong, Shu Xuan; Toh, Serene Hui Fang; Khong, Ming Hui; Yeo, Anna C H; Au Eong, Kah-Guan

2014-08-01

To re-evaluate the awareness of age-related macular degeneration (AMD) and knowledge of its risk factors among Singapore residents after 5 years of awareness campaigns. Cross-sectional, questionnaire-based telephone survey (modified from the AMD Alliance International Global Report), conducted in Singapore in 2011. Participants were randomly selected using the Global Yellow Pages Singapore residential listings 2009/2010. Awareness of AMD and its risk factors was assessed among participants. Of 1773 Singapore residents contacted over the telephone, 559 participated (31.5% response rate). The mean age of participants was 43.1 years (range 21-85 years). A total of 157 participants (28.1%) were familiar with AMD. Among these, the number who correctly identified the risk factors were: smoking, n = 132 (84.1%); ageing, n = 123 (78.3%); lack of vitamins/nutrients, n = 121 (77.1%); genetics, n = 101 (64.3%); unprotected light exposure, n = 100 (63.7%) and; sex, n = 62 (39.5%). Participants aged >50 years (prevalence rate ratio, PRR 2.23, confidence interval, CI, 1.31-3.81) or who had undergone an eye test within the previous year (PRR 2.61, 95% CI 1.79-3.82) were more familiar with AMD, while females (PRR 0.68, 95% CI 0.47-0.98) were less familiar. Self-reported awareness of AMD among Singapore residents increased four-fold from 7.3% in 2006 to 28.1% in 2011 following 5 years of awareness campaigns. Participants who were >50 years or had undergone an eye test within the previous year were more aware of AMD while female participants were less aware of AMD.

Determinants for Sensitivity of Human Immunodeficiency Virus Coreceptor CXCR4 to the Bicyclam AMD3100

PubMed Central

Labrosse, Béatrice; Brelot, Anne; Heveker, Nikolaus; Sol, Nathalie; Schols, Dominique; De Clercq, Erik; Alizon, Marc

1998-01-01

The bicyclam AMD3100 is a potent and selective inhibitor of the replication of human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2). It was recently demonstrated that the compound inhibited HIV entry through CXCR4 but not through CCR5. Selectivity of AMD3100 for CXCR4 was further indicated by its lack of effect on HIV-1 and HIV-2 infection mediated by the CCR5, CCR3, Bonzo, BOB, and US28, coreceptors. AMD3100 completely blocked HIV-1 infection mediated by a mutant CXCR4 bearing a deletion of most of the amino-terminal extracellular domain. In contrast, relative resistance to AMD3100 was conferred by different single amino acid substitutions in the second extracellular loop (ECL2) or in the adjacent membrane-spanning domain, TM4. Only substitutions of a neutral residue for aspartic acid and of a nonaromatic residue for phenylalanine (Phe) were associated with drug resistance. This suggests a direct interaction of AMD3100 with these amino acids rather than indirect effects of their mutation on the CXCR4 structure. The interaction of aspartic acids of ECL2 and TM4 with AMD3100 is consistent with the positive charge of bicyclams, which might block HIV-1 entry by preventing electrostatic interactions between CXCR4 and the HIV-1 envelope protein gp120. Other features of AMD3100 must account for its high antiviral activity, in particular the presence of an aromatic linker between the cyclam units. This aromatic group might engage in hydrophobic interactions with the Phe-X-Phe motifs of ECL2 or TM4. These results confirm the importance of ECL2 for the HIV coreceptor activity of CXCR4. PMID:9658078

Sunlight exposure, pigmentation, and incident age-related macular degeneration.

PubMed

Klein, Barbara E K; Howard, Kerri P; Iyengar, Sudha K; Sivakumaran, Theru A; Meyers, Kristin J; Cruickshanks, Karen J; Klein, Ronald

2014-08-14

Examine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD. Subjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color. Incidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD. Modest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Risk of macular degeneration affected by polymorphisms in Matrix metalloproteinase-2: A case-control study in Chinese Han population.

PubMed

Cheng, Jie; Hao, Xiaolin; Zhang, Zhongchen

2017-11-01

The purpose of this study was to investigate the correlation of single nucleotide polymorphisms (SNPs) in Matrix metalloproteinase -2 (MMP-2) gene and the risk of age-related macular degeneration (AMD) in Chinese Han population.A total of 126 AMD patients and 141 healthy controls participated in this study. Genotypes of MMP-2 gene polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). χtest was used to detect the differences of genotypes and alleles frequencies between case and control groups. Relative risk of AMD was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs).Distribution of variant allele carriers (computed tomography + TT genotypes) of MMP-2 gene rs243865 SNP was significantly different between case and control groups, and might act as protective factors for the onset of AMD (P = .044, OR = 0.583, 95% CI = 0.344-0.987). Nevertheless, the T allele might reduce the AMD risk (P = .030, OR = 0.611, 95% CI = 0.390-0.956). However, no significant association existed between rs243865 and AMD risk in the subgroup analysis based on age. GA + AA genotypes of rs243866 SNP may associate with a decreased risk of AMD in the age≤65 years subgroup (P = .028, OR = 0.399, 95% CI = 0.174-0.915).MMP-2 gene rs243865 and rs243866 SNPs associated with the risk of AMD. Further studies should be performed to confirm the results. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

PDT: special cases in front of legal regulations

NASA Astrophysics Data System (ADS)

Fischer, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

2002-10-01

Introduction: The classic indication for photodynamic therapy (PDT) in ophthalmology is currently represented by classic subfoveal choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). PDT is a method, which almost selectively causes endothelial damage in neovascular lesions, followed by vascular occlusion and involution of the CNV. The mechanistic aspect suggests that non AMD-related choroidal neovascularisations might also benefit from PDT. PDT in AMD: Within the German health system, PDT indications follow the criteria based on the inclusion criteria of the TAP studies. For instance the CNV should be predominantly classic and located under the center of the foveal avascular zone. In the diagnosis and follow-up of exudative AMD, visual acuity measurements and fluorescein angiography are the established parameters. Retinal thickness analyzer (RTA) measurements might give further information. Before PDT, they show a significant retinal thickening due to intra- and subretinal exudation. Following PDT, early RTA follow-ups show a clear decrease in retinal thickening accompanies by increasing or stable acuity. PDT in CNV of other origins than AMD: New studies support a new spectrum of indications for PDT, hopefully leading to general cost reimbursement for patients. PDT should be viewed as a general method for vascular occlusion and does not represent a causal therapy for progressive exudative AMD. We present patients with CNV due to pathologic myopia, angioid streaks and POHS. Conclusion: The selective vascular occlusion caused by PDT, besides CNV associated with AMD and pathologic myopia, may also allow the treatment of choroidal neovascularisations based on other entities. Careful individual evaluation of those cases is recommended. Despite this wide array of possible indications, cost reimbursement has been limited to classic subfoveal CNV in AMD, although single case reimbursements in choroidal neovascular lesions due to pathologic myopia have been observed.

Rare genetic variants in Tunisian Jewish patients suffering from age-related macular degeneration.

PubMed

Pras, Eran; Kristal, Dana; Shoshany, Nadav; Volodarsky, Dina; Vulih, Inna; Celniker, Gershon; Isakov, Ofer; Shomron, Noam; Pras, Elon

2015-07-01

To explore the molecular basis of familial, early onset, age-related macular degeneration (AMD) with diverse phenotypes, using whole exome sequencing (WES). We performed WES on four patients (two sibs from two families) manifesting early-onset AMD and searched for disease-causing genetic variants in previously identified macular degeneration related genes. Validation studies of the variants included bioinformatics tools, segregation analysis of mutations within the families and mutation screening in an AMD cohort of patients. The index patients were in their 50s when diagnosed and displayed a wide variety of clinical AMD presentations: from limited drusen in the posterior pole to multiple basal-laminar drusen extending peripherally. Severe visual impairment due to extensive geographic atrophy and/or choroidal-neovascularisation was common by the age of 75 years. Approximately, 400 000 genomic variants for each DNA sample were included in the downstream bioinformatics analysis, which ended in the discovery of two novel variants; in one family a single bp deletion was identified in the Hemicentin (HMCN1) gene (c.4162delC), whereas in the other, a missense variant (p.V412M) in the Complement Factor-I (CFI) gene was found. Screening for these variants in a cohort of patients with AMD identified another family with the CFI variant. This report uses WES to uncover rare genetic variants in AMD. A null-variant in HMCN1 has been identified in one AMD family, and a missense variant in CFI was discovered in two other families. These variants confirm the genetic complexity and significance of rare genetic variants in the pathogenesis of AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pesticide Use and Age-Related Macular Degeneration in the Agricultural Health Study

PubMed Central

Montgomery, Martha P.; Postel, Eric; Umbach, David M.; Richards, Marie; Watson, Mary; Blair, Aaron; Chen, Honglei; Sandler, Dale P.; Schmidt, Silke

2017-01-01

Background: Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. Few studies have investigated its relationship to environmental neurotoxicants. In previous cross-sectional studies, we found an association between pesticide use and self-reported retinal degeneration. Objective: We evaluated the association of pesticide use with physician-confirmed incident AMD. Methods: The Agricultural Health Study (AHS) is a prospective cohort of pesticide applicators and their spouses enrolled from 1993–1997 in Iowa and North Carolina. Cohort members reported lifetime use of 50 specific pesticides at enrollment. Self-reports of incident AMD during follow-up through 2007 were confirmed by reports from participants’ physicians and by independent evaluation of retinal photographs provided by the physicians. Confirmed cases (n=161) were compared with AHS cohort members without AMD (n=39,108). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression with adjustment for age, gender, and smoking. Results: AMD was associated with ever use of organochlorine [OR=2.7 (95% CI: 1.8, 4.0)] and organophosphate [OR=2.0 (95% CI: 1.3, 3.0)] insecticides and phenoxyacetate herbicides [OR=1.9 (95% CI: 1.2, 2.8)]. Specific pesticides consistently associated with AMD included chlordane, dichlorodiphenyltrichloroethane (DDT), malathion, and captan; others with notable but slightly less consistent associations were heptachlor, diazinon, phorate, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,4-dichlorophenoxyacetic acid (2,4-D). Results were similar for men and women. Some specific pesticides were associated with both early- and late-stage AMD, but others were associated with only one stage. Conclusions: Exposures to specific pesticides may be modifiable risk factors for AMD. https://doi.org/10.1289/EHP793 PMID:28886597

The Relationship of Major American Dietary Patterns to Age-related Macular Degeneration

PubMed Central

Chiu, Chung-Jung; Chang, Min-Lee; Zhang, Fang Fang; Li, Tricia; Gensler, Gary; Schleicher, Molly; Taylor, Allen

2014-01-01

PURPOSE We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. DESIGN Cross-sectional study METHODS 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early AMD (n=4,599), and advanced AMD (n=765) by AREDS AMD Classification System. Food consumption data were collected by a 90-item food frequency questionnaire. RESULTS Two major dietary patterns were identified by factor (principle component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the two patterns by calculating the two factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O=0.74 (95% confidence interval (CI): 0.59–0.91; Ptrend=0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W=1.56 (1.18–2.06; Ptrend=0.01). For advanced AMD, the ORA5O was 0.38 (0.27–0.54; Ptrend<0.0001), and the ORA5W was 3.70 (2.31–5.92; Ptrend<0.0001). CONCLUSIONS Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. PMID:24792100

The relationship of major American dietary patterns to age-related macular degeneration.

PubMed

Chiu, Chung-Jung; Chang, Min-Lee; Zhang, Fang Fang; Li, Tricia; Gensler, Gary; Schleicher, Molly; Taylor, Allen

2014-07-01

We hypothesized that major American dietary patterns are associated with risk for age-related macular degeneration (AMD). Cross-sectional study. We classified 8103 eyes in 4088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS). They were classified into control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765) by the AREDS AMD Classification System. Food consumption data were collected by using a 90-item food frequency questionnaire. Two major dietary patterns were identified by factor (principal component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the 2 patterns by calculating the 2 factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O = 0.74 (95% confidence interval (CI): 0.59-0.91; Ptrend =0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W = 1.56 (1.18-2.06; Ptrend = 0.01). For advanced AMD, the ORA5O was 0.38 (0.27-0.54; Ptrend < 0.0001), and the ORA5W was 3.70 (2.31-5.92; Ptrend < 0.0001). Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic studies of Age-related macular degeneration: lessons, challenges and opportunities for disease management

PubMed Central

Ratna Priya, Rinki; Chew, Emily Y.; Swaroop, Anand

2012-01-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals over 55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic and non-genetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from human genome project, genomewide association studies and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Here, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher a new era of personalized medicine in the clinical management of AMD. PMID:23009893

Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

PubMed Central

DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

2014-01-01

Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

Interleukin-17 retinotoxicity is prevented by gene transfer of a soluble interleukin-17 receptor acting as a cytokine blocker: implications for age-related macular degeneration.

PubMed

Ardeljan, Daniel; Wang, Yujuan; Park, Stanley; Shen, Defen; Chu, Xi Kathy; Yu, Cheng-Rong; Abu-Asab, Mones; Tuo, Jingsheng; Eberhart, Charles G; Olsen, Timothy W; Mullins, Robert F; White, Gary; Wadsworth, Sam; Scaria, Abraham; Chan, Chi-Chao

2014-01-01

Age-related macular degeneration (AMD) is a common yet complex retinal degeneration that causes irreversible central blindness in the elderly. Pathology is widely believed to follow loss of retinal pigment epithelium (RPE) and photoreceptor degeneration. Here we report aberrant expression of interleukin-17A (IL17A) and the receptor IL17RC in the macula of AMD patients. In vitro, IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes with subsequent activation of pro-apoptotic Caspase-3 and Caspase-9. This pathology is reduced by siRNA knockdown of IL17RC. IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor. This intervention rescues RPE and photoreceptors in a MAPK-dependent process. The IL17 pathway plays a key role in RPE and photoreceptor degeneration and could hold therapeutic potential in AMD.

Lighting Needs and Lighting Comfort During Reading with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Fosse, Per; Valberg, Arne

2004-01-01

This study investigated the effects of changes in luminance on the oral reading speeds of 13 participants with age-related macular degeneration (AMD) and a control group of six age-matched persons with typical vision. For the AMD participants, self-reports of light preferences were also recorded. In the AMD group, reading rates depended on light…

A Historical Analysis of the Quest for the Origins of Aging Macula Disorder, the Tissues Involved, and Its Terminology

PubMed Central

de Jong, Paulus T.V.M.

2016-01-01

Although ocular tissues involved in aging macula disorder (AMD) were already known in 300 BC, the last type of photoreceptors was discovered only 10 years ago. The earliest descriptions of AMD appeared around 1850. It took over 150 years, till a clearer concept of AMD was formulated and even longer to grasp its pathophysiology. The uncertainty of researchers about the pathogenesis of AMD over the last century is reflected in its changing terminology. The evolution of this terminology is provided in a table to afford the reader a better insight into explanations proposed by researchers during this quest. PMID:27812291

Response of hydroponically grown head lettuce on residual monomer from polyacrylamide.

PubMed

Mroczek, E; Konieczny, P; Kleiber, T; Waśkiewicz, A

2014-01-01

The aim was to assess acrylamide monomer (AMD) uptake by hydroponically grown lettuce. Lettuce was cultivated by applying plant tissue testing in a recycled system by the use of nutrient solutions prepared with two water-soluble flocculants F3 and F4 containing 176 and 763 mg kg(-1) of AMD, respectively. The effects on growth, fresh weight and plant leaf quality were evaluated by comparing these treatments and one control standard nutrient solution typically recommended for lettuce hydroponic cultivation. To assess the nutritional status of lettuce, samples were collected and lyophilised before determination of the selected micro- and macro-element contents. An HPLC with photodiode array detector method was applied to determine AMD in both selected flocculants and dried plant samples. Results show that lettuces cultivated under the conditions described above absorb AMD from nutrient solutions into their leaves. The AMD presence in recycled nutrient solutions has a negative influence on the growth of lettuce, reducing their average fresh weight and average number of leaves. The study confirmed that the problem of AMD mobility and its accumulation risk in plants should to be an important topic with respect to safe polyacrylamide (PAM) handling in the agro food area.

[Quality of life in patients with age-related macular degeneration - medical and social problem].

PubMed

Muzyka-Woźniak, Maria; Misiuk-Hojło, Marta; Wesolowska, Alicja

2011-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness over the age of 50 in western countries. People with AMD are suffering from serious vision-related disability and their social life is compromised. The aim of our study was to assess quality of life (QoL) in patients with exudative AMD. The study group was 100 patients treated for AMD, the control group were 30 age and sex matched subjects without ophthalmic disorders. Patients were treated with anti-VEGF therapy, by means of National Eye Institute Visual Function Questionnaire (NEI VFQ-25). As well as visual function, the NEI-VFQ investigates social functioning, mental health and dependency. There was statistically significant difference in QoL overall score between study group and control group. Patients with AMD obtained 51.1 (+/- 20.5 ) overall score, control group reached 83.7 (+/- 11.7) overall score, p = 0.001. Detailed analysis of study group revealed low acceptance of the disease and strong dependency. QoL in patients with AMD assessed with NEI VFQ-25, is significantly impaired. Low quality of life and difficulties in performing daily activities point at the need of formal psychological and social care.

Accelerated molecular dynamics simulations of protein folding.

PubMed

Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

2015-07-30

Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

PubMed Central

2016-01-01

Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD. PMID:27695506

Corneal thickness of eyes with unilateral age-related macular degeneration.

PubMed

Arikan, Sedat; Ersan, Ismail; Kara, Selcuk; Gencer, Baran; Korkmaz, Safak; Vural, Azer Sara

2015-01-01

To compare the central corneal thicknesses (CCT), peripheral corneal thicknesses, and corneal volumes (CV) of the 2 eyes of patients with unilateral age-related macular degeneration (AMD). Twenty patients who were diagnosed with unilateral AMD were included in this prospective study for the purpose of making comparison between the diseased and healthy eyes. Optical coherence tomography and fundus fluorescein angiography imaging were applied to all patients in order to confirm and reveal the presence of unilateral AMD. Then, the measurements of CCT, peripheral corneal thickness measured 4 mm distant from the center of the cornea (4 mm CT), and CV of each eye of these patients were obtained through the rotating Scheimpflug corneal topographer. Wilcoxon signed-rank test did not demonstrate a statistically significant difference between the 2 eyes of patients with unilateral AMD when we compared the CCT and CV of diseased and healthy eyes (p>0.05). However, 4 mm CT of the diseased eyes of these patients were statistically significantly thicker than the healthy eyes (p<0.05). The significant difference in terms of 4 mm CT between the diseased and healthy eyes of patients with unilateral AMD may demonstrate the possible effect of peripheral corneal thickness on the development of AMD.

Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.

PubMed

Wykoff, Charles C; Clark, W Lloyd; Nielsen, Jared S; Brill, Joel V; Greene, Laurence S; Heggen, Cherilyn L

2018-02-01

The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients. Three anti-VEGF therapies currently form the mainstay of treatment for nAMD, including 2 therapies approved by the FDA for treatment of nAMD (aflibercept and ranibizumab) and 1 therapy approved by the FDA for oncology indications and used off-label for treatment of nAMD (bevacizumab). In clinical trials, each of the 3 agents maintained visual acuity (VA) in approximately 90% or more of nAMD patients over 2 years. However, in long-term and real-world settings, significant gaps and challenges in diagnosis, treatment, and management pose barriers to achieving optimal outcomes for patients with nAMD. Many considerations, including individual patient characteristics, on-label versus off-label treatment, repackaging, and financial considerations, add to the complexity of nAMD decision making and management. Many factors may contribute to additional challenges leading to suboptimal long-term outcomes among nAMD patients, such as delays in diagnosis and/or treatment approval and initiation, individual patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring. These latter factors highlight the considerable logistical, emotional, and financial burdens of long-term, frequent intravitreal injections and the vital importance of personalized approaches to anti-VEGF treatment decision making and management for patients with nAMD. To address these challenges and reduce the number of yearly injections, studies have examined alternative dosing regimens, including extended fixed intervals, as needed, and treat-and-extend strategies in specific nAMD patient populations. New clinical evidence and insights into expert clinical practice discussed in this article can support managed care professionals in the key role they play in addressing challenges in nAMD treatment and management and optimizing patient outcomes through appropriate management of anti-VEGF treatment. PRIME Education is an independent medical education company and has been an accredited provider of continuing education for 23 years. There is no fee for this activity as it is sponsored by PRIME through an educational grant from Regeneron. All authors contributed to the writing and reviewing of the article. Wykoff reports consultancies/research grants from Alcon Laboratories, Genentech/Roche, Clearside, and Iconic Therapeutics; consultancies/honoraria, research grants, and speaker fees from Allergan and Regeneron; research grants from Allegro, Apellis, Aura, NEI, NIH, Novartis, OHR Pharmaceuticals, Ophthotech, pSivida, Roche, Santen, SciFluor, Tyrogenex; and consultancies for Alimera Sciences, Alnylam Pharmaceuticals, Bayer, DORC, ONL Therapeutics, Thrombogenics, and Valeant. Clark reports advisory board work, consultancies, research grants, and speaker fees from Genentech/Roche and Regeneron and consultancy for Bayer. Brill reports consultancies for Aries Pharma, Avella, BaroNova, Braeburn Pharmaceuticals, Cardinal Health, Endogastric Solutions, GeneNews, Halt Medical, Lumendi, Medtronic, Monteris Medical, Natera, Phosphorus, Rebiotix, Seno Medical, UCB, Vermillion, Echosens, and HAP Innovations. Brill is a shareholder in EndoChoice, GeneNews, SonarMD, and SynerZ and reports advisory board work with Nestle Health Sciences, Indivior Pharmaceuticals, Eli Lilly, Blue Earth Diagnostics, Bayer, and AstraZeneca. Nielson reports advisory board work/consultancy and research grants for Genentech/Roche; advisory board work and research grants from Regeneron; and research grants from Alcon and Ophthotech.

Size and performance of anoxic limestone drains to neutralize acdic mine drainagei

USGS Publications Warehouse

Cravotta, C.A.

2003-01-01

Acidic mine drainage (AMD) can be neutralized effectively in underground, anoxic limestone drains (ALDs). Owing to reaction between the AMD and limestone (CaCO3), the pH and concentrations of alkalinity and calcium increase asymptotically with detention time in the ALD, while concentrations of sulfate, ferrous iron, and manganese typically are unaffected. This paper introduces a method to predict the alkalinity produced within an ALD and to estimate the mass of limestone required for its construction on the basis of data from short-term, closed-container (cubitainer) tests. The cubitainer tests, which used an initial mass of 4 kg crushed limestone completely inundated with 2.8 L AMD, were conducted for 11 to 16 d and provided estimates for the initial and maximum alkalinities and corresponding rates of alkalinity production and limestone dissolution. Long-term (5-11 yr) data for alkalinity and CaCO3 flux at the Howe Bridge, Morrison, and Buck Mountain ALDs in Pennsylvania, USA, indicate that rates of alkalinity production and limestone dissolution under field conditions were comparable with those in cubitainers filled with limestone and AMD from each site. The alkalinity of effluent and intermediate samples along the flow path through the ALDs and long-term trends in the residual mass of limestone and the effluent alkalinity were estimated as a function of the computed detention time within the ALD and second-order dissolution rate models for cubitainer tests. Thus, cubitainer tests can be a useful tool for designing ALDs and predicting their performance.

Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

PubMed Central

Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

2016-01-01

Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

Prevalence and risk factors for age-related macular degeneration in Indians: a comparative study in Singapore and India.

PubMed

Gemmy Cheung, Chui Ming; Li, Xiang; Cheng, Ching-Yu; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B; Nangia, Vinay; Wong, Tien Yin

2013-04-01

To compare the prevalence and risk factors for age-related macular degeneration (AMD) in 2 Indian populations, 1 living in urban Singapore and 1 in rural central India. Population-based, cross-sectional studies of Indians aged 40+ years. Our analysis included 3337 Singapore-residing participants and 3422 India-residing participants. All participants underwent comprehensive systemic and ocular examinations and retinal photography. AMD was graded from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Systemic and ocular risk factors were assessed for association with AMD. Singapore-residing participants were older (mean age 57.8 years vs 53.8 years) and, after adjusting for age and sex, were more likely to have previous cataract surgery, higher body mass index, hypertension, diabetes, previous myocardial infarction, higher cholesterol, and lower creatinine levels, but less likely to be current smokers, than India-residing participants. The age-standardized prevalence of early and late AMD was 4.45% and 0.34%, respectively, in Singapore and 5.80% and 0.16%, respectively, in India. Shorter axial length was associated with early AMD in both Singapore and India, whereas previous cataract surgery, higher body mass index, hypertension, and lower cholesterol were associated with early AMD in Singapore but not in India. The prevalence of AMD was similar among Indian adults living in urban Singapore and rural India, despite differences in cardiovascular risk factor profile and demographics. Copyright © 2013 Elsevier Inc. All rights reserved.

GeoChip-Based Analysis of the Functional Gene Diversity and Metabolic Potential of Microbial Communities in Acid Mine Drainage▿ †

PubMed Central

Xie, Jianping; He, Zhili; Liu, Xinxing; Liu, Xueduan; Van Nostrand, Joy D.; Deng, Ye; Wu, Liyou; Zhou, Jizhong; Qiu, Guanzhou

2011-01-01

Acid mine drainage (AMD) is an extreme environment, usually with low pH and high concentrations of metals. Although the phylogenetic diversity of AMD microbial communities has been examined extensively, little is known about their functional gene diversity and metabolic potential. In this study, a comprehensive functional gene array (GeoChip 2.0) was used to analyze the functional diversity, composition, structure, and metabolic potential of AMD microbial communities from three copper mines in China. GeoChip data indicated that these microbial communities were functionally diverse as measured by the number of genes detected, gene overlapping, unique genes, and various diversity indices. Almost all key functional gene categories targeted by GeoChip 2.0 were detected in the AMD microbial communities, including carbon fixation, carbon degradation, methane generation, nitrogen fixation, nitrification, denitrification, ammonification, nitrogen reduction, sulfur metabolism, metal resistance, and organic contaminant degradation, which suggested that the functional gene diversity was higher than was previously thought. Mantel test results indicated that AMD microbial communities are shaped largely by surrounding environmental factors (e.g., S, Mg, and Cu). Functional genes (e.g., narG and norB) and several key functional processes (e.g., methane generation, ammonification, denitrification, sulfite reduction, and organic contaminant degradation) were significantly (P < 0.10) correlated with environmental variables. This study presents an overview of functional gene diversity and the structure of AMD microbial communities and also provides insights into our understanding of metabolic potential in AMD ecosystems. PMID:21097602

Identification of nitrogen-fixing genes and gene clusters from metagenomic library of acid mine drainage.

PubMed

Dai, Zhimin; Guo, Xue; Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan

2014-01-01

Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community.

Plasma metabolomic study in Chinese patients with wet age-related macular degeneration.

PubMed

Luo, Dan; Deng, Tingting; Yuan, Wei; Deng, Hui; Jin, Ming

2017-09-06

Age-related macular degeneration (AMD) is a leading disease associated with blindness. It has a high incidence and complex pathogenesis. We aimed to study the metabolomic characteristics in Chinese patients with wet AMD by analyzing the morning plasma of 20 healthy controls and 20 wet AMD patients for metabolic differences. We used ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry for this analysis. The relationship of these differences with AMD pathophysiology was also assessed. Remaining data were normalized using Pareto scaling, and then valid data were handled using multivariate data analysis with MetaboAnalysis software, including unsupervised principal component analysis and supervised partial least squares-discriminate analysis. The purpose of the present work was to identify significant metabolites for the analyses. Hierarchical clustering was conducted to identify metabolites that differed between the two groups. Significant metabolites were then identified using the established database, and features were mapped on the Kyoto Encyclopedia of Genes and Genomes. A total of 5443 ion peaks were detected, all of them attributable to the same 10 metabolites. These included some amino acids, isomaltose, hydrocortisone, and biliverdin. The heights of these peaks differed significantly between the two groups. The biosynthesis of amino acids pathways also differed profoundly between patients with wet AMD and controls. These findings suggested that metabolic profiles and and pathways differed between wet AMD and controls and may provide promising new targets for AMD-directed therapeutics and diagnostics.

Identification of Nitrogen-Fixing Genes and Gene Clusters from Metagenomic Library of Acid Mine Drainage

PubMed Central

Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan

2014-01-01

Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community. PMID:24498417

Effect of ambient light and age-related macular degeneration on precision walking.

PubMed

Alexander, M Scott; Lajoie, Kim; Neima, David R; Strath, Robert A; Robinovitch, Stephen N; Marigold, Daniel S

2014-08-01

To determine how age-related macular degeneration (AMD) and changes in ambient light affect the control of foot placement while walking. Ten older adults with AMD and 11 normal-sighted controls performed a precision walking task under normal (∼600 lx), dim (∼0.7 lx), and after a sudden reduction (∼600 to 0.7 lx) of light. The precision walking task involved subjects walking and stepping to the center of a series of irregularly spaced, low-contrast targets. Habitual visual acuity and contrast sensitivity and visual field function were also assessed. There were no differences between groups when performing the walking task in normal light (p > 0.05). In reduced lighting, older adults with AMD were less accurate and more variable when stepping across the targets compared to controls (p < 0.05). A sudden reduction of light proved the most challenging for this population. In the AMD group, contrast sensitivity and visual acuity were not significantly correlated with walking performance. Visual field thresholds in the AMD group were only associated with greater foot placement error and variability in the dim light walking condition (r = -0.69 to -0.87, p < 0.05). While walking performance is similar between groups in normal light, poor ambient lighting results in decreased foot placement accuracy in older adults with AMD. Improper foot placement while walking can lead to a fall and possible injury. Thus, to improve the mobility of those with AMD, strategies to enhance the environment in reduced lighting situations are necessary.

Age-related macular degeneration changes the processing of visual scenes in the brain.

PubMed

Ramanoël, Stephen; Chokron, Sylvie; Hera, Ruxandra; Kauffmann, Louise; Chiquet, Christophe; Krainik, Alexandre; Peyrin, Carole

2018-01-01

In age-related macular degeneration (AMD), the processing of fine details in a visual scene, based on a high spatial frequency processing, is impaired, while the processing of global shapes, based on a low spatial frequency processing, is relatively well preserved. The present fMRI study aimed to investigate the residual abilities and functional brain changes of spatial frequency processing in visual scenes in AMD patients. AMD patients and normally sighted elderly participants performed a categorization task using large black and white photographs of scenes (indoors vs. outdoors) filtered in low and high spatial frequencies, and nonfiltered. The study also explored the effect of luminance contrast on the processing of high spatial frequencies. The contrast across scenes was either unmodified or equalized using a root-mean-square contrast normalization in order to increase contrast in high-pass filtered scenes. Performance was lower for high-pass filtered scenes than for low-pass and nonfiltered scenes, for both AMD patients and controls. The deficit for processing high spatial frequencies was more pronounced in AMD patients than in controls and was associated with lower activity for patients than controls not only in the occipital areas dedicated to central and peripheral visual fields but also in a distant cerebral region specialized for scene perception, the parahippocampal place area. Increasing the contrast improved the processing of high spatial frequency content and spurred activation of the occipital cortex for AMD patients. These findings may lead to new perspectives for rehabilitation procedures for AMD patients.

Iris colour, ethnic origin and progression of age-related macular degeneration.

PubMed

Nicolas, Caroline M; Robman, Luba D; Tikellis, Gabriella; Dimitrov, Peter N; Dowrick, Adam; Guymer, Robyn H; McCarty, Catherine A

2003-12-01

To investigate the relationship between iris colour, ethnic origin and the progression of age-related macular degeneration (AMD). Participants were recruited from the population-based Melbourne Visual Impairment Project or the prospective, randomized, double-masked Vitamin E, Cataract and Age-Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992-1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants' iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants' grandparents' country of birth. In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age-adjusted and multivariate-adjusted associations were not significant (both P = 0.13). Age-adjusted and multivariate comparisons of Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable but non-significant association with progression of AMD (P= 0.22 and P= 0.14, respectively). Individuals with light iris colour or of Anglo-Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger sample is required to confirm these clinically important, but statistically non-significant, associations.

Effect of Soluble Inducible Costimulator Level and Its Polymorphisms on Age-Related Macular Degeneration

PubMed Central

Yu, Honghua; Zou, Xiulan; Peng, Lianghong; Wang, Yong; Zhang, Chu

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease. PMID:24083358

Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

PubMed

Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

2018-02-01

Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

PubMed Central

Ardeljan, Daniel; Chan, Chi-Chao

2013-01-01

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

Physical Activity and Age-related Macular Degeneration: A Systematic Literature Review and Meta-analysis.

PubMed

McGuinness, Myra B; Le, Jerome; Mitchell, Paul; Gopinath, Bamini; Cerin, Ester; Saksens, Nicole T M; Schick, Tina; Hoyng, Carel B; Guymer, Robyn H; Finger, Robert P

2017-08-01

To better understand the association, in a white population, of physical activity and age-related macular degeneration (AMD)-the main cause of irreversible severe vision loss in developed countries-given the suggestion that a healthy lifestyle may assist in delaying the onset and progression of AMD. Systematic review and meta-analysis. Medline, EMBASE, and Google Scholar were systematically searched for studies up to May 2015. Reference lists of published articles were hand searched and study authors were contacted to provide additional data. Those in the lowest category of activity in each study were compared with all other participants to assess the association between physical activity and both early and late AMD using random-effects meta-analysis. Nine studies (subject age range 30-97 years) were included in the meta-analysis. Physical activity was found to have a protective association with both early AMD (8 studies, n = 38 112, odds ratio (OR) 0.92, 95% confidence interval [CI] 0.86-0.98) and late AMD (7 studies, n = 28 854, OR 0.59, 95% CI 0.49-0.72). Physical activity is associated with lower odds of early and late AMD in white populations. These findings have important implications, reinforcing the public health message of staying active throughout life. However, further longitudinal studies are required to confirm and further characterize a protective effect of physical activity on the onset and/or progression of AMD. Copyright © 2017 Elsevier Inc. All rights reserved.

Ground-State Properties of Mg Isotopes in and Beyond the Island of Inversion through Reaction Cross Sections

NASA Astrophysics Data System (ADS)

Watanabe, Shin; Minomo, Kosho; Shimada, Mitsuhiro; Tagami, Shingo; Kimura, Masaaki; Takechi, Maya; Fukuda, Mitsunori; Nishimura, Daiki; Suzuki, Takeshi; Matsumoto, Takuma; Shimizu, Yoshifumi R.; Yahiro, Masanobu

We analyze recently measured total reaction cross sections (σR) for 24-38Mg incident on 12C targets at 240 MeV/nucleon by using the microscopic framework based on the double folding model and antisymmetrized molecular dynamics (AMD). The framework reproduces not only the measured σR but also other existing measured ground-state properties of Mg Isotopes (spin parity, total binding energy, one-neutron separation energy, and 2+ and 4+ excitation energies) quite well. AMD predicts large deformation from 31Mg19 to a drip-line nucleus 40Mg28, indicating that both the N = 20 and 28 magicities disappear.

Characterizing the hydrological system in Rosia Montana mining area (Romania) for AMD mitigation

NASA Astrophysics Data System (ADS)

Cozma, Alexandra; Baciu, Calin; Olenici, Adriana; Brahaita, Dorian; Pop, Cristian; Lazar, Laura; Roba, Carmen; Popita, Gabriela

2015-04-01

Keywords: mining, AMD mitigation, isotopic analyses, Romania Rosia Montana is one of the most important European gold fields, with a long history of mining. The extraction of gold started on site during the Roman age, and the mining operations that spanned over almost two millennia have produced a visible environmental footprint. More than 140 km of mining galleries are documented by historical sources and recent surveys. Water streams are the main vectors spreading the pollution outside the mining area. The main streams, Rosia, Corna, and Saliste, tributaries of Abruzel River are significantly impacted by the acid waters issued by adits, exposed rock surfaces, or rock waste heaps, and tailings depots. Low contamination has been observed in the streams outside the mining area, artificial ponds, and shallow groundwater. Excepting the shallow groundwater system that can be sampled in domestic wells and some springs, the circulation of groundwater is largely unknown. An important amount of the infiltration water is channelled through galleries. The waters sampled at the galleries outlets have low pH, generally between 2 and 3, and very high content of heavy metals. A systematic approach based on monthly sampling and chemical analyses, and isotopic measurements, has been initiated, in order to better understand the underground itinerary of water and the chemical transformations that occur. A sampling network of 28 water points, including streams, ponds, dug wells, springs, and gallery outlets has been setup. Beyond producing a water circulation model in the mining area, the main purpose of the research is to identify ways of decreasing the acid water production and to design low cost techniques for the AMD mitigation. The deposit still hosts about 300 tonnes of gold, and 1600 tonnes of silver. A new large scale mining project is currently under permitting. Cost-effective solutions for the water treatment would be beneficial, especially for the post-mining stage of any future operation. Acknowledgments: The present contribution was financially supported by a grant of the Romanian National Authority for Scientific Research, CCCDI - UEFISCDI, project 3-005 Tools for sustainable gold mining in EU (SUSMIN). Dorian Brahaita has benefited from the financial support provided by the project POSDRU/159/1.5/S/132400.

Estimating the Prevalence of Anxiety and Mood Disorders in an Adolescent General Population: An Evaluation of the GHQ12

ERIC Educational Resources Information Center

Mann, Robert E.; Paglia-Boak, Angela; Adlaf, Edward M.; Beitchman, Joseph; Wolfe, David; Wekerle, Christine; Hamilton, Hayley A.; Rehm, Jurgen

2011-01-01

Anxiety and mood disorders (AMD) may be more common among adolescents than previously thought, and epidemiological research would benefit from an easily-administered measure of AMD. We assessed the ability of the GHQ12 to estimate the prevalence of AMD in a representative sample of Ontario adolescents. Data were based on self-administered…

Knowledge and Use of Low Vision Services Among Persons with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Casten, Robin J.; Maloney, Eileen K.; Rovner, Barry W.

2005-01-01

Visual impairment (blindness or low vision) is a leading cause of disability among older adults and is most often due to age-related macular degeneration (AMD). It is predicted that 2.95 million people will have AMD by 2020 (Eye Diseases Prevalence Research Group, 2004). Unfortunately, there is no cure for AMD, nor can lost vision be restored.…

Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study

PubMed Central

2013-01-01

Background Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170). Methods Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. Results The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background. Conclusions There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD. PMID:23302509

miRNA involvement in angiogenesis in age-related macular degeneration.

PubMed

Wang, Lei; Lee, Amy Yi Wei; Wigg, Jonathan P; Peshavariya, Hitesh; Liu, Ping; Zhang, Hong

2016-12-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Late-stage AMD is characterized by choroidal neovascularization (CNV). miR-93 appears to play a role in regulating vascular endothelial growth factor-A (VEGF-A), a known factor involved in neovascularization. Understanding its biological significance might enable development of therapeutic interventions for diseases like AMD. We aimed to determine the role of miR-93 in AMD using a laser-induced CNV mouse model. CNV was induced by laser photocoagulation in C57BL/6 mice. The CNV mice were transfected with scrambled miR or miR-93 mimic. The treatment effect was assessed by fundus photography and fluorescein angiography and confirmed by choroidal flatmount. The expression of miR-93 and VEGF-A in ocular tissues was analysed by quantitative polymerase chain reaction (qPCR) and Western blot. The overexpression effects of miR-93 were also proved on human microvascular endothelial cells (HMECs). Significantly decreased expression of miR-93 was observed by qPCR analysis in CNV mice compared to untreated mice (p < 0.05). VEGF-A messenger RNA (mRNA) and protein expression were upregulated with CNV; these changes were ameliorated by restoration of miR-93 (p < 0.05). CNV was reduced after miR-93 transfection. Transfection of miR-93 reduced the proliferation of HMECs (p < 0.01), but no significant changes were observed in 2D capillary-like tube formation (p > 0.05) and migration (p > 0.05) compared with that in the untreated cells. miR-93 has been shown to be a negative modulator of angiogenesis in the eye. All together, these results highlight the therapeutic potential of miR-93 and suggest that it may contribute as a putative therapeutic target for AMD in humans.

Geographic and Demographic Variation in Use of Ranibizumab Versus Bevacizumab for Neovascular Age-related Macular Degeneration in the United States.

PubMed

Gower, Emily W; Stein, Joshua D; Shekhawat, Nakul S; Mikkilineni, Shravani; Blachley, Taylor S; Pajewski, Nicholas M

2017-12-01

To examine demographic and geographic variation in the use of ranibizumab and bevacizumab for the treatment of neovascular age-related macular degeneration (AMD) among Medicare beneficiaries. Retrospective cohort study. Using a 100% sample of Medicare claims data, we evaluated Medicare beneficiaries (N = 195 812) with an index claim for neovascular AMD between July 1, 2006, and June 30, 2009, to determine whether beneficiaries first received ranibizumab or bevacizumab following initial diagnosis. The overall proportion of beneficiaries that first received ranibizumab for neovascular AMD was 35%, and varied significantly (0.9%-84.6%) across the 306 US hospital referral regions (median = 33%, interquartile range = 17%-49%). Based on hierarchical logistic regression models, the likelihood of receiving ranibizumab declined over time (adjusted odds ratio (aOR) comparing treatment in 2009 vs 2006 = 0.39, P < .001). After we controlled for year of treatment, black beneficiaries were 45% less likely to receive ranibizumab compared to non-blacks (P < .0001). Beneficiaries residing in urban areas (aOR vs isolated rural towns = 1.12, P < .001), in zip codes with higher median incomes, and in the New England and East South Central census regions (aOR vs Pacific census region = 5.57, P < .001; aOR = 3.58, P < .001, respectively) had increased odds of receiving ranibizumab. The odds of receiving bevacizumab vs ranibizumab as initial therapy for neovascular AMD among US Medicare beneficiaries varied substantially across geographic and demographic groups. Relatively fewer patients received ranibizumab for initial neovascular AMD treatment in 2009 vs 2006. Future research should study the drivers of variation in utilization of these interventions, the extent this variation indicates differential access to these agents, and whether treatment choice impacts patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect.

PubMed

Kumar, Sanjay; Ponnazhagan, Selvarangan

2012-04-01

Although the number of mesenchymal stem cells (MSC) in the bone marrow is sufficient to maintain skeletal homeostasis, in osteopenic pathology, aggravated osteoclast activity or insufficient osteoblast numbers ensue, affecting normal bone remodeling. Most of the currently available therapies are anti-resorptive with limited osteogenic potential. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in tissue repair, amplification of endogenous stem cells may provide an alternative approach in these conditions. The present study determined the potential of MSC mobilization in vivo, using combinations of different growth factors with the CXCR4 antagonist, AMD3100, in a mouse model of segmental bone defect. Results indicated that among several factors tested IGF1 had maximum proliferative ability of MSC in vitro. Results of the in vivo studies indicated that the combination of IGF1 and AMD3100 provided significant augmentation of bone growth as determined by DXA, micro-CT and histomorphometry in mice bearing segmental fractures. Further, characterization of MSC isolated from mice treated with IGF1 and AMD3100 indicated Akt/PI3K, MEK1/2-Erk1/2 and smad2/3 as key signaling pathways mediating this effect. These data indicate the potential of in vivo stem cell mobilization as a novel alternative for bone healing. Copyright © 2012 Elsevier Inc. All rights reserved.

The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PubMed

Sharma, S; Brown, G C; Brown, M M; Hollands, H; Shah, G K

2001-11-01

Photodynamic therapy (PDT) has recently been demonstrated to be beneficial for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Herein, we determine the cost-effectiveness of PDT for the treatment of subfoveal choroidal neovascularization (CNV) in patients with disciform degeneration in one eye and whose second and better-seeing eye develops visual loss secondary to predominantly classic subfoveal CNV. The analysis was performed from the perspective of a for-profit third-party insurer. Cost-utility Markov models were created to determine the cost-effectiveness of PDT under two different scenarios, by using efficacy data derived from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study and patient-based utilities. Decision analyses were performed by incorporating data from the TAP Study, expected longevity data, and patient-based utilities. Cost-effective models were then created by incorporating incremental medical costs. Various sensitivity analyses were carried out to determine the robustness of our models. A Monte Carlo simulation was also used to determine whether there was a significant difference in quality-of-life adjusted years (QALYs) gained between PDT therapy and the placebo. For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/40 vision at baseline in this affected eye (base case 1), PDT was associated with a 10.7% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.1342 QALYs over a 2-year period). For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/200 vision at baseline in this affected eye (base case 2), PDT was associated with a 7.8% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.0669 QALYs over a 2-year period). Sensitivity analysis showed our models were robust and that PDT was usually the dominant treatment choice. Our cost-effective model demonstrated that the cost for a QALY was $86,721 (US dollars discounted at 3%) for base case 1, assuming 5.5 treatments; and $173,984 (USD discounted at 3%) for base case 2. PDT will cost a third-party insurer $86,721 for an AMD patient with 20/40 vision in the better-seeing eye to obtain one QALY and $173,984 for an AMD patient with 20/200 vision in the better-seeing eye to obtain one QALY. PDT can be considered to be a treatment that is of only minimal cost-effectiveness for AMD patients who have subfoveal CNV in their second and better-seeing eyes and who have good presenting visual acuity at baseline. It is a cost-ineffective treatment for AMD patients who have poor visual acuities in their affected better-seeing eyes.

Role of the vitreous in age-related macular degeneration.

PubMed

Ondeş, F; Yilmaz, G; Acar, M A; Unlü, N; Kocaoğlan, H; Arsan, A K

2000-01-01

To investigate the relationship between posterior vitreous detachment (PVD) and age-related macular degeneration (AMD). The condition of the vitreous was examined by slit-lamp funduscopy and ultrasonography in 93 eyes of 50 patients with AMD (exudative or dry) and 100 eyes of 50 controls. There was complete PVD in 31 of the 93 eyes (33.3%) of 50 patients with AMD and the posterior vitreous was attached in 62 of these eyes (66.6%). In the control group, in 50 eyes (50%) of 50 subjects there was posterior vitreous detachment. The prevalence of PVD in eyes with macular degeneration was significantly lower (P < .05). There was no statistically significant difference between the exudative and the nonexudative groups in respect to PVD. PVD may have a protective role against the development of AMD. Chronic vitreomacular traction and/or continuous exposure to free radicals and cytokines may possibly be one of the causes of AMD in eyes with attached vitreous.

Genetic studies of age-related macular degeneration: lessons, challenges, and opportunities for disease management.

PubMed

Priya, Rinki Ratna; Chew, Emily Y; Swaroop, Anand

2012-12-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals >55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic, and nongenetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from the human genome project, genome-wide association studies, and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Herein, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive, and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher in a new era of personalized medicine in the clinical management of AMD. Proprietary or commercial disclosures may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Application of acid mine drainage for coagulation/flocculation of microalgal biomass.

PubMed

Salama, El-Sayed; Kim, Jung Rae; Ji, Min-Kyu; Cho, Dong-Wan; Abou-Shanab, Reda A I; Kabra, Akhil N; Jeon, Byong-Hun

2015-06-01

A novel application of acid mine drainage (AMD) for biomass recovery of two morphologically different microalgae species with respect to AMD dosage, microalgal cell density and pH of medium was investigated. Optimal flocculation of Scenedesmus obliquus and Chlorella vulgaris occurred with 10% dosage of AMD at an initial pH 9 for both 0.5 and 1.0 g/L cell density. The flocculation efficiency was 89% for S. obliquus and 93% for C. vulgaris. Zeta potential (ZP) was increased from -10.66 to 1.77 and -13.19 to 1.33 for S. obliquus and C. vulgaris, respectively. Scanning electron microscope with energy-dispersive X-ray of the microalgae floc confirmed the sweeping floc formation mechanism upon the addition of AMD. Application of AMD for the recovery of microalgae biomass is a cost-effective method, which might further allow reuse of flocculated medium for algal cultivation, thereby contributing to the economic production of biofuel from microalgal biomass. Copyright © 2015 Elsevier Ltd. All rights reserved.

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

PubMed Central

Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

2016-01-01

As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

Efficacy of vitrectomy and epiretinal membrane peeling in eyes with dry age-related macular degeneration.

PubMed

Mason, John O; Patel, Shyam A

2015-01-01

To study the efficacy of epiretinal membrane (ERM) peeling in eyes with dry age-related macular degeneration (AMD). We retrospectively analyzed patient charts on 17 eyes (16 patients) that underwent ERM peeling with a concurrent diagnosis of dry AMD. Eyes with concurrent dry AMD and with a good preoperative best-corrected visual acuity (BCVA) (better than or equal to 20/50) had a statistically significant mean BCVA improvement at 6 months after ERM peeling. There was a statistical increase in mean BCVA from 20/95 to 20/56 in dry AMD eyes, and no eyes showed worsening in BCVA at 6 months or at most recent follow-up. Five/seventeen (29.4%) eyes had cataract formation or progression. There were no other complications, reoperations, or reoccurrences. ERM peeling in eyes with dry AMD may show significant improvement, especially in eyes with good preoperative BCVA. The procedure is relatively safe with low complications and reoccurrences.

Unrealistic representations of "the self": A cognitive neuroscience assessment of anosognosia for memory deficit.

PubMed

Berlingeri, Manuela; Ravasio, Alessandra; Cranna, Silvia; Basilico, Stefania; Sberna, Maurizio; Bottini, Gabriella; Paulesu, Eraldo

2015-12-01

Three cognitive components may play a crucial role in both memory awareness and in anosognosia for memory deficit (AMD): (1) a personal data base (PDB), i.e., a memory store that contains "semantic" representations about the self, (2) monitoring processes (MPs) and (3) an explicit evaluation system (EES), or comparator, that assesses and binds the representations stored in the PDB with information obtained from the environment. We compared both the behavior and the functional connectivity (as assessed by resting-state fMRI) of AMD patients with aware patients and healthy controls. We found that AMD is associated with an impoverished PDB, while MPs are necessary to successfully update the PDB. AMD was associated with reduced functional connectivity within both the default-mode network and in a network that includes the left lateral temporal cortex, the hippocampus and the insula. The reduced connectivity between the hippocampus and the insular cortex was correlated with AMD severity. Copyright © 2015 Elsevier Inc. All rights reserved.

Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain.

PubMed

Yang, Ruimeng; Duan, Chong; Yuan, Liya; Engelbach, John A; Tsien, Christina I; Beeman, Scott C; Perez-Torres, Carlos J; Ge, Xia; Rich, Keith M; Ackerman, Joseph J H; Garbow, Joel R

2018-03-15

There is mounting evidence that, in addition to angiogenesis, hypoxia-induced inflammation via the hypoxia-inducible factor 1α (HIF-1α)-CXC chemokine receptor 4 (CXCR4) pathway may contribute to the pathogenesis of late-onset, irradiation-induced necrosis. This study investigates the mitigative efficacy of an HIF-1α inhibitor, topotecan, and a CXCR4 antagonist, AMD3100, on the development of radiation necrosis (RN) in an intracranial mouse model. Mice received a single-fraction, 50-Gy dose of hemispheric irradiation from the Leksell Gamma Knife Perfexion and were then treated with either topotecan, an HIF-1α inhibitor, from 1 to 12 weeks after irradiation, or AMD3100, a CXCR4 antagonist, from 4 to 12 weeks after irradiation. The onset and progression of RN were monitored longitudinally via noninvasive, in vivo magnetic resonance imaging (MRI) from 4 to 12 weeks after irradiation. Conventional hematoxylin-eosin staining and immunohistochemistry staining were performed to evaluate the treatment response. The progression of brain RN was significantly mitigated for mice treated with either topotecan or AMD3100 compared with control animals. MRI-derived lesion volumes were significantly smaller for both of the treated groups, and histologic findings correlated well with the MRI data. By hematoxylin-eosin staining, both treated groups demonstrated reduced irradiation-induced tissue damage compared with controls. Furthermore, immunohistochemistry results revealed that expression levels of vascular endothelial growth factor, CXC chemokine ligand 12, CD68, CD3, and tumor necrosis factor α in the lesion area were significantly lower in treated (topotecan or AMD3100) brains versus control brains, while ionized calcium-binding adapter molecule 1 (Iba1) and HIF-1α expression was similar, though somewhat reduced. CXCR4 expression was reduced only in topotecan-treated mice, while interleukin 6 expression was unaffected by either topotecan or AMD3100. By reducing inflammation, both topotecan and AMD3100 can, independently, mitigate the development of RN in the mouse brain. When combined with first-line, antiangiogenic treatment, anti-inflammation therapy may provide an adjuvant therapeutic strategy for clinical, postirradiation management of tumors, with additional benefits in the mitigation of RN development. Copyright © 2017 Elsevier Inc. All rights reserved.

Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration.

PubMed

Ethen, Cheryl M; Feng, Xiao; Olsen, Timothy W; Ferrington, Deborah A

2005-03-01

Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

Characterization of Fe(II) oxidizing bacterial activities and communities at two acidic Appalachian coalmine drainage-impacted sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senko, John M.; Wanjugi, Pauline; Lucas, Melanie

2008-06-12

We characterized the microbiologically mediated oxidative precipitation of Fe(II) from coalminederived acidic mine drainage (AMD) along flow-paths at two sites in northern Pennsylvania. At the Gum Boot site, dissolved Fe(II) was efficiently removed from AMD whereas minimal Fe(II) removal occurred at the Fridays-2 site. Neither site received human intervention to treat the AMD. Culturable Fe(II) oxidizing bacteria were most abundant at sampling locations along the AMD flow path corresponding to greatest Fe(II) removal and where overlying water contained abundant dissolved O2. Rates of Fe(II) oxidation determined in laboratory-based sediment incubations were also greatest at these sampling locations. Ribosomal RNA intergenicmore » spacer analysis and sequencing of partial 16S rRNA genes recovered from sediment bacterial communities revealed similarities among populations at points receiving regular inputs of Fe(II)-rich AMD and provided evidence for the presence of bacterial lineages capable of Fe(II) oxidation. A notable difference between bacterial communities at the two sites was the abundance of Chloroflexi-affiliated 16S rRNA gene sequences in clone libraries derived from the Gum Boot sediments. Our results suggest that inexpensive and reliable AMD treatment strategies can be implemented by mimicking the conditions present at the Gum Boot field site.« less

Nature and nurture- genes and environment- predict onset and progression of macular degeneration.

PubMed

Sobrin, Lucia; Seddon, Johanna M

2014-05-01

Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages. Both environmental and genetic factors contribute to the development of this disease. Among environmental factors, smoking, obesity and dietary factors including antioxidants and dietary fat intake influence onset and progression of AMD. There are also several lines of evidence that link cardiovascular, immune and inflammatory biomarkers to AMD. The genetic etiology of AMD has been and continues to be an intense and fruitful area of investigation. Genome-wide association studies have revealed numerous common variants associated with AMD and sequencing is increasing our knowledge of how rare genetic variants strongly impact disease. Evidence for interactions between environmental, therapeutic and genetic factors is emerging and elucidating the mechanisms of this interplay remains a major challenge in the field. Genotype-phenotype associations are evolving. The knowledge of non-genetic, modifiable risk factors along with information about heritability and genetic risk variants for this disease acquired over the past 25 years have greatly improved patient management and our ability to predict which patients will develop or progress to advanced forms of AMD. Personalized medicine and individualized prevention and treatment strategies may become a reality in the near future. Copyright © 2014. Published by Elsevier Ltd.

Mechanism of Inflammation in Age-Related Macular Degeneration

PubMed Central

Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

2012-01-01

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

Recent developments in age-related macular degeneration: a review

PubMed Central

Al-Zamil, Waseem M; Yassin, Sanaa A

2017-01-01

Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

Physical activity and the 15-year incidence of age-related macular degeneration.

PubMed

Gopinath, Bamini; Liew, Gerald; Burlutsky, George; Mitchell, Paul

2014-11-11

There is uncertainty in the published literature as to whether physical activity should be advocated for age-related macular degeneration (AMD) prevention. We aimed to assess prospectively the association between physical activity and the 15-year incidence of AMD in older adults. We assessed AMD from retinal photographs. Participants provided details of walking exercise and the performance of moderate or vigorous activities, which were used to calculate metabolic equivalents (METs). After adjusting for age, adults aged ≥ 75 years in the highest tertile (the most physically active) compared to those in the lowest tertile (least physically active) were 79% less likely to have incident late AMD over the 15 years (odds ratio [OR], 0.21; 95% confidence intervals [CI], 0.05-0.95). However, after further adjusting for sex, body mass index, smoking, fish consumption, and white cell count, this association was no longer statistically significant (OR, 0.26; 95% CI, 0.06-1.28). Significant associations were not found in those aged <75 or with the 15-year cumulative incidence of early AMD. Physical activity did not influence the risk of AMD over 15 years in older adults, independent of diet, smoking, white cell count, and body mass index. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Sequestration of phosphorus by acid mine drainage floc

USGS Publications Warehouse

Adler, P.R.; Sibrell, P.L.

2003-01-01

Solubilization and transport of phosphorus (P) to the water environment is a critical environmental issue. Flocs resulting from neutralizing acid mine drainage (AMD) were tested as a possible lowcost amendment to reduce the loss of soluble P from agricultural fields and animal wastewater. Flocs were prepared by neutralizing natural and synthetic solutions of AMD with limestone, lime, ammonium hydroxide, and sodium hydroxide. Phosphorus sequestration was tested in three distinct environments: water, soil, and manure storage basins. In water, flocs prepared from AMD adsorbed 10 to 20 g P kg-1 dry floc in equilibrium with 1 mg L-1 soluble P. Similar results were observed for both Fe-based and A1-based synthetic flocs. A local soil sample adsorbed about 0.1 g P kg-1, about two orders of magnitude less. The AMD-derived flocs were mixed with a highP soil at 5 to 80 g floc kg-1 soil, followed by water and acid (Mehlich1) extractions. All flocs performed similarly. About 70% of the waterextractable P was sequestered by the floc when applied at a rate of 20 g floc kg-1 soil, whereas plant-available P only decreased by about 30%. Under anaerobic conditions simulating manure storage basins, all AMD flocs reduced soluble P by greater than 95% at a rate of 0.2 g floc g-1 rainbow trout (Oncorhynchus mykiss) manure. These findings indicate that AMD flocs could be an effective agent for preventing soluble P losses from soil and manure to the water environment, while at the same time decreasing the costs associated with AMD treatment.

Intraocular Vascular Endothelial Growth Factor Levels in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration.

PubMed

Hata, Masayuki; Yamashiro, Kenji; Ooto, Sotaro; Oishi, Akio; Tamura, Hiroshi; Miyata, Manabu; Ueda-Arakawa, Naoko; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

2017-01-01

To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. This study included nine eyes with treatment-naïve pachychoroid neovasculopathy and 21 eyes with treatment-naïve nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

Are Lung Disease and Function Related to Age-related Macular Degeneration?

PubMed Central

Moorthy, Sonia; Cheung, Ning; Klein, Ronald; Shahar, E; Wong, Tien Y

2010-01-01

Purpose To describe the relationship of lung disease and function with early age-related macular degeneration (AMD) in a population-based study. Design A population-based, cross-sectional study of 12,596 middle-aged participants from the Atherosclerosis Risk in Communities Study. Methods Lung function was assessed by spirometry. Physician diagnosis of asthma and lung disease was ascertained from a standardized questionnaire. AMD signs were graded from fundus photographs according to the Wisconsin grading protocol. Results Of our study population, 587 (4.7%) had early AMD, 638 (5.1%) had asthma and 581 (4.6%) had lung disease. After adjusting for age, gender, smoking and hypertension, each litre increase in predicted forced expiratory volume in one second (FEV1) (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.89, 1.80), forced vital capacity (FVC) (OR 1.18; 95% CI: 0.93, 1.51) and peak expiratory flow rate (OR 1.12; 95% CI: 0.95, 1.33) were not significantly associated with early AMD. FEV1/FVC ratio (second quartile OR 1.61; 95%CI 0.88–2.93, third quartile OR 1.65; CI 0.90–3.03, fourth quartile OR 1.28; 95%CI 0.68–2.40) was not significantly associated with early AMD. Similarly, asthma (OR 1.06; 95% CI: 0.86, 1.27) and other lung diseases (OR 1.08; 95% CI: 0.90, 1.29) were not associated with early AMD. Conclusion Our data do not support a cross-sectional association between lung disease and risk of early AMD. PMID:21168814

Hydrogeochemical features of surface water and groundwater contaminated with acid mine drainage (AMD) in coal mining areas: a case study in southern Brazil.

PubMed

Galhardi, Juliana Aparecida; Bonotto, Daniel Marcos

2016-09-01

Effects of acid mine drainage (AMD) were investigated in surface waters (Laranjinha River and Ribeirão das Pedras stream) and groundwaters from a coal mining area sampled in two different seasons at Figueira city, Paraná State, Brazil. The spatial data distribution indicated that the acid effluents favor the chemical elements leaching and transport from the tailings pile into the superficial water bodies or aquifers, modifying their quality. The acid groundwaters in both sampling periods (dry: pH 2.94-6.04; rainy: pH 3.25-6.63) were probably due to the AMD generation and infiltration, after the oxidation of sulfide minerals. Such acid effluents cause an increase of the solubilization rate of metals, mainly iron and aluminum, contributing to both groundwater and surface water contamination. Sulfate in high levels is a result of waters' pollution due to AMD. In some cases, high sulfate and low iron contents, associated with less acidic pH values, could indicate that AMD, previously generated, is nowadays being neutralized. The chemistry of the waters affected by AMD is controlled by the pH, sulfide minerals' oxidation, oxygen, iron content, and microbial activity. It is also influenced by seasonal variations that allow the occurrence of dissolution processes and the concentration of some chemical elements. Under the perspective of the waters' quality evaluation, the parameters such as conductivity, dissolved sodium, and sulfate concentrations acted as AMD indicators of groundwaters and surface waters affected by acid effluents.

[Influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration (AMD)].

PubMed

Włodarek, Dariusz; Głabska, Dominika

2011-01-01

The aim of the study was analysis of the influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration The object of conducted analysis were 127 nutrition questionnaires from 64 individuals with AMD (44 female, 20 male) and 63 without AMD--control group (49 female, 14 male). The age of participants was 50-88. The nutrition questionnaire concerned: AMD and its course, consumption of lutein-rich products and lutein supplementation. Lutein supply was assessed on the base of most often consumed products and lutein content in typical servings as well as on the base of applied supplementation. Patients with AMD, in comparison with control group, were significantly more often choosing green bean, parsley, dill (Anethum graveolens) and young beetroot leaves, as well as were consuming more diversified lutein-rich products. Lutein supply from diet was significanly increased in case of spinach consumption (very high in lutein) and broccoli consumption (high in lutein and chosen relatively often). Other products did not cause increase of lutein supply from diet, even if they evoked increase of lutein content in the typical serving or of quantity of servings. Patients with AMD, in comparison with healthy individuals, more often consume lutein-rich products, but lutein supply from diet in both groups do not differ. Significant increase of lutein supply may be achieved only by consumption of products characterized by the highest content of it. Patients with AMD, in comparison with healthy individuals, more often apply lutein supplementation, that influences lutein daily supply.

A new primary mobility tool for the visually impaired: A white cane-adaptive mobility device hybrid.

PubMed

Rizzo, John-Ross; Conti, Kyle; Thomas, Teena; Hudson, Todd E; Wall Emerson, Robert; Kim, Dae Shik

2017-05-16

This article describes pilot testing of an adaptive mobility device-hybrid (AMD-H) combining properties of two primary mobility tools for people who are blind: the long cane and adaptive mobility devices (AMDs). The long cane is the primary mobility tool used by people who are blind and visually impaired for independent and safe mobility and AMDs are adaptive devices that are often lightweight frames approximately body width in lateral dimension that are simply pushed forward to clear the space in front of a person. The prototype cane built for this study had a wing apparatus that could be folded around the shaft of a cane but when unfolded, deployed two wheeled wings 25 cm (9.8 in) to each side of the canetip. This project explored drop-off and obstacle detection for 6 adults with visual impairment using the deployed AMD-H and a standard long cane. The AMD-H improved obstacle detection overall, and was most effective for the smallest obstacles (2 and 6 inch diameter). The AMD-H cut the average drop off threshold from 1.79 inches (4.55 cm) to .96 inches (2.44 cm). All participants showed a decrease in drop off detection threshold and an increase in detection rate (13.9% overall). For drop offs of 1 in (2.54 cm) and 3 in (7.62 cm), all participants showed large improvements with the AMD-H, ranging from 8.4 to 50%. The larger drop offs of 5 in (12.7 cm) and 7 in (17.8 cm) were well detected by both types of canes.

Detection of Early Loss of Color Vision in Age-Related Macular Degeneration - With Emphasis on Drusen and Reticular Pseudodrusen.

PubMed

Vemala, Roopa; Sivaprasad, Sobha; Barbur, John L

2017-05-01

To evaluate chromatic sensitivity in patients with age-related macular degeneration (AMD) characterized by drusen and reticular pseudodrusen. To investigate whether the severity of color vision loss can distinguish between various stages of AMD and hence be used as an index of progression toward advanced AMD. Chromatic sensitivity was measured by using the Color Assessment and Diagnosis (CAD) test in asymptomatic individuals with early and intermediate AMD and compared to normative data. All study participants had logMAR visual acuity of 0.3 or better. The CAD thresholds measured in eyes with and without reticular pseudodrusen were also compared and related to central macular thickness (CMT). Student's t-test P values < 0.05 were considered significant. All early- and intermediate-AMD eyes (n = 90) had chromatic sensitivity loss in either RG (red/green) or YB (yellow/blue), or both (P < 0.0001) as compared to age-matched normal subjects. The eyes exhibited a range of CAD thresholds affecting both color mechanisms, but YB color thresholds were in general higher than RG thresholds (P < 0.001). Intermediate-AMD patients exhibited large intersubject variability. In general, eyes with reticular pseudodrusen and eyes with CMT < 200 μm had significantly higher CAD thresholds. The anatomic integrity of cone photoreceptors remains relatively unaffected in early and intermediate stages of AMD. The processing of cone signals in the retina can, however, be heavily disrupted with subsequent loss of both YB and RG chromatic sensitivity. The greatest losses were observed in eyes with reticular pseudodrusen.

Toward earlier detection of choroidal neovascularization secondary to age-related macular degeneration: multicenter evaluation of a preferential hyperacuity perimeter designed as a home device.

PubMed

Loewenstein, Anat; Ferencz, Joseph R; Lang, Yaron; Yeshurun, Itamar; Pollack, Ayala; Siegal, Ruth; Lifshitz, Tova; Karp, Joseph; Roth, Daniel; Bronner, Guri; Brown, Justin; Mansour, Sam; Friedman, Scott; Michels, Mark; Johnston, Richards; Rapp, Moshe; Havilio, Moshe; Rafaeli, Omer; Manor, Yair

2010-01-01

The primary purpose of this study was to evaluate the ability of a home device preferential hyperacuity perimeter to discriminate between patients with choroidal neovascularization (CNV) and intermediate age-related macular degeneration (AMD), and the secondary purpose was to investigate the dependence of sensitivity on lesion characteristics. All participants were tested with the home device in an unsupervised mode. The first part of this work was retrospective using tests performed by patients with intermediate AMD and newly diagnosed CNV. In the second part, the classifier was prospectively challenged with tests performed by patients with intermediate AMD and newly diagnosed CNV. The dependence of sensitivity on lesion characteristics was estimated with tests performed by patients with CNV of both parts. In 66 eyes with CNV and 65 eyes with intermediate AMD, both sensitivity and specificity were 0.85. In the retrospective part (34 CNV and 43 intermediate AMD), sensitivity and specificity were 0.85 +/- 0.12 (95% confidence interval) and 0.84 +/- 0.11 (95% confidence interval), respectively. In the prospective part (32 CNV and 22 intermediate AMD), sensitivity and specificity were 0.84 +/- 0.13 (95% confidence interval) and 0.86 +/- 0.14 (95% confidence interval), respectively. Chi-square analysis showed no dependence of sensitivity on type (P = 0.44), location (P = 0.243), or size (P = 0.73) of the CNV lesions. A home device preferential hyperacuity perimeter has good sensitivity and specificity in discriminating between patients with newly diagnosed CNV and intermediate AMD. Sensitivity is not dependent on lesion characteristics.

Visual Function Metrics in Early and Intermediate Dry Age-related Macular Degeneration for Use as Clinical Trial Endpoints.

PubMed

Cocce, Kimberly J; Stinnett, Sandra S; Luhmann, Ulrich F O; Vajzovic, Lejla; Horne, Anupama; Schuman, Stefanie G; Toth, Cynthia A; Cousins, Scott W; Lad, Eleonora M

2018-05-01

To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD. Cross-sectional analysis of baseline data from a prospective study. One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments (best-corrected visual acuity, macular integrity assessment mesopic microperimety, dark adaptometry, low-luminance visual acuity [LLVA] [standard using a log 2.0 neutral density filter and computerized method], and cone contrast test [CCT]) were performed. Low-luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs low luminance. Group comparisons were performed to evaluate differences between the control and the early and intermediate AMD groups using 2-sided significance tests. Functional measures that significantly distinguished between normal and intermediate AMD were standard and computerized (0.5 cd/m 2 ) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (P < .05). The intermediate group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2, and dark adaptation (P < .05) relative to early AMD. Our study suggests that LLVA, microperimetry, CCT, and dark adaptation may serve as functional measures differentiating early-to-intermediate stages of dry AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

α-Lipoic Acid Treatment Improves Vision-Related Quality of Life in Patients with Dry Age-Related Macular Degeneration.

PubMed

Tao, Yuan; Jiang, Pengfei; Wei, Yuhua; Wang, Ping; Sun, Xiaoling; Wang, Hong

2016-11-01

Dry form of age-related macular degeneration (AMD) constitutes 90% of AMD cases, and it is characterized by the formation of drusen under the retina and the slow breakdown of the light-sensing cells in the macula, which causes a gradual loss of central vision. Since oxidative stress is involved in the pathogenesis of dry AMD, α-lipoic acid (LA) with antioxidant properties was selected, and its effect on anti-oxidative markers and visual quality in patients with dry AMD was assessed. A total of 100 dry AMD patients (60-83 years old) were randomly assigned to LA treatment group (n = 50) and placebo control group (n = 50). We measured the serum superoxide dismutase (SOD) activity, an important marker of antioxidant defense, best-corrected visual acuity (BCVA), contrast sensitivity, and Chinese-Version Low Vision Quality of Life (CLVQOL) before and after LA or placebo intervention. Pearson correlation coefficients were calculated to explore the relationship between contrast sensitivity values and CLVQOL scores. There was a statistically significant increase in serum SOD activity after LA intervention. The CLVQOL score was improved significantly after LA treatment. The contrast sensitivity measured at middle and low spatial frequency was significantly higher after LA treatment. CLVQOL scores were positively correlated with contrast sensitivity at low spatial frequency (3 cyc/degree) in LA-treated group. These results indicate that LA treatment improves vision-related quality of life in patients with dry AMD probably by increasing antioxidant activity. Thus, LA can be regarded as a promising agent for the treatment of AMD.

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PubMed

Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

2017-07-01

To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

PubMed

Matsumoto, Hidetaka; Hiroe, Takashi; Morimoto, Masahiro; Mimura, Kensuke; Ito, Arisa; Akiyama, Hideo

2018-03-01

To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.

Investigating the CFH Gene Polymorphisms as a Risk Factor for Age-related Macular Degeneration in an Iranian Population.

PubMed

Babanejad, Mojgan; Moein, Hamidreza; Akbari, Mohammad R; Badiei, Azadeh; Yaseri, Mehdi; Soheilian, Masoud; Najmabadi, Hossein

2016-06-01

Age-related macular degeneration (AMD) is a complex disorder which results in irreversible vision loss and progressive impairment of central vision. Disease susceptibility is influenced by multiple genetic and environmental factors. Single nucleotide polymorphisms (SNP) in the complement factor H gene are the most important genetic risk factors. We conducted a case-control study to investigate the association four SNPs (dbSNP ID: rs800292, rs1061170, rs2274700 and rs3753395) of CFH gene with AMD in the Iranian population. We recruited 100 AMD patients and 100 age- and sex-matched normal controls. Direct sequencing for three SNPs (rs800292, rs2274700 and rs3753395) and restriction fragment length polymorphism utilized for rs1061170. Allele and genotype frequencies of SNPs were calculated and tested for departure from Hardy-Weinberg equilibrium using the Chi-square test. An allelic and genotypic association was compared by logistic regression analysis using the SNPassoc. According to our results, the frequencies of risk allele for all SNPs (G, G, A, and C alleles of rs800292, rs2274700, rs3753395 and rs1061170, respectively) were significantly higher in AMD patients (p value < 0.001). AMD individuals who had at least one copy of the C allele of rs1061170 had an increased risk of disease compared with cases with the T allele. Other studied polymorphisms showed the same association. Our results suggest the contribution of all four predicted CFH polymorphisms in AMD susceptibility among the Iranian population. This association with CFH may lead to early detection and new strategies for prevention and treatment of AMD.

Removal of sulphates acidity and iron from acid mine drainage in a bench scale biochemical treatment system.

PubMed

Prasad, D; Henry, J G

2009-02-01

The focus of this study was to develop a simple biochemical system to treat acid mine drainage for its safe disposal. Recovery and reuse of the metals removed were not considered. A three-step process for the treatment of acid mine drainage (AMD), proposed earlier, separates sulphate reducing activity from metal precipitation units and from a pH control system. Following our earlier work on the first step (biological reactor), this paper examines the second step (i.e. chemical reactor). The objectives of this study were: (1) to determine the increase in pH and the reduction of iron in the chemical reactor for different proportions of simulated AMD, and (2) to assess the capability of the chemical reactor. A series of experiments was conducted to study the effects of addition of alkaline sulphidogenic liquor (ASL) derived from a batch sulphidogenic biological reactor (operating with activated sludge and a COD/SO4 ratio of 1.6) on the simulated AMD characteristics. At 60-minute contact time, addition of 30% ASL (pH of 7.60-7.76) to the chemical reactor with 70% AMD (pH of 1.65-2.02), increased the pH of the AMD to 6.57 and alkalinity from 0 to 485 mg l(-1) as CaCO3, respectively and precipitated about 97% of the iron present in the simulated AMD. Others have demonstrated that metals in mine drainage can be precipitated by bacterial sulphate reduction. In this study, iron, a common and major component of mine drainage was used as a surrogate for metals in general. The results indicate the feasibility of treating AMD by an engineered sulphidogenic anaerobic reactor followed by a chemical reactor and that our three-step biochemical process has important advantages over other conventional AMD treatment systems.

Visual function assessment in simulated real-life situations in patients with age-related macular degeneration compared to normal subjects.

PubMed

Barteselli, G; Gomez, M L; Doede, A L; Chhablani, J; Gutstein, W; Bartsch, D-U; Dustin, L; Azen, S P; Freeman, W R

2014-10-01

To evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA). Overall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions. Vision drop across environments was calculated, and repeatability of visual scores was determined. BCVA significantly reduced with decreasing contrast in all eyes. M1 scores for BCVA were greater than M2 and M3 (P<0.001); G1 scores were greater than G2 and G3 (P<0.01). BCVA dropped more in AMD eyes than in normal eyes between M1 and M2 (P=0.002) and between M1 and M3 (P=0.003). In AMD eyes, BCVA was better using ETDRS charts compared to G1 (P<0.001). The drop in visual function between ETDRS and G1 was greater in AMD eyes compared to normal eyes (P=0.004). Standard deviations of test-retest ranged from 0.100 to 0.139 logMAR. The CVA allowed analysis of the visual complaints that AMD patients experience with different lighting/contrast time-dependent conditions. BCVA changed significantly under different lighting/contrast conditions in all eyes, however, AMD eyes were more affected by contrast reduction than normal eyes. In AMD eyes, timed conditions using the CVA led to worse BCVA compared to non-timed ETDRS charts.

Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis

PubMed Central

Dong, Yonghui; Liu, Hui; Zhang, Xuejun; Xu, Fei; Qin, Liang; Cheng, Peng; Huang, Hui; Guo, Fengjing; Yang, Qing; Chen, Anmin

2016-01-01

Previous studies showed that SDF-1α is a catabolic factor that can infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity. Inhibiting the SDF-1α/CXCR4 signalling pathway can attenuate the pathogenesis of osteoarthritis (OA). Recent studies have also shown that SDF-1α enhances chondrocyte proliferation and maturation. These results appear to be contradictory. In the current study, we used a destabilisation OA animal model to investigate the effects of SDF-1α/CXCR4 signalling in the tibial subchondral bone and the OA pathological process. Post-traumatic osteoarthritis (PTOA) mice models were prepared by transecting the anterior cruciate ligament (ACLT), or a sham surgery was performed, in a total of 30 mice. Mice were treated with phosphate buffer saline (PBS) or AMD3100 (an inhibitor of CXCR4) and sacrificed at 30 days post ACLT or sham surgery. Tibial subchondral bone status was quantified by micro-computed tomography (μCT). Knee-joint histology was analysed to examine the articular cartilage and joint degeneration. The levels of SDF-1α and collagen type I c-telopeptidefragments (CTX-I) were quantified by ELISA. Bone marrow mononuclear cells (BMMCs) were used to clarify the effects of SDF-1α on osteoclast formation and activity in vivo. μCT analysis revealed significant loss of trabecular bone from tibial subchondral bone post-ACLT, which was effectively prevented by AMD3100. AMD3100 could partially prevent bone loss and articular cartilage degeneration. Serum biomarkers revealed an increase in SDF-1α and bone resorption, which were also reduced by AMD3100. SDF-1α can promote osteoclast formation and the expression oftartrate resistant acid phosphatase (TRAP), cathepsin K (CK), and matrix metalloproteinase (MMP)-9 in osteoclasts by activating the MAPK pathway, including ERK and p38, but not JNK. In conclusion, inhibition of SDF-1α/CXCR4signalling was able to prevent trabecular bone loss and attenuated cartilage degeneration in PTOA mice. PMID:27322244

Intra-vitreal αB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration.

PubMed

Sreekumar, Parameswaran G; Li, Zhe; Wang, Wan; Spee, Christine; Hinton, David R; Kannan, Ram; MacKay, J Andrew

2018-05-18

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible central vision loss, and the primary site of AMD pathology is the retinal pigment epithelium (RPE). Geographic atrophy (GA) is an advanced form of AMD characterized by extensive RPE cell loss, subsequent degeneration of photoreceptors, and thinning of retina. This report describes the protective potential of a peptide derived from the αB crystallin protein using a sodium iodate (NaIO 3 ) induced mouse model of GA. Systemic NaIO 3 challenge causes degeneration of the RPE and neighboring photoreceptors, which have similarities to retinas of GA patients. αB crystallin is an abundant ocular protein that maintains ocular clarity and retinal homeostasis, and a small peptide from this protein (mini cry) displays neuroprotective properties. To retain this peptide for longer in the vitreous, mini cry was fused to an elastin-like polypeptide (ELP). A single intra-vitreal treatment by this crySI fusion significantly inhibits retinal degeneration in comparison to free mini cry. While mini cry is cleared from the eye with a mean residence time of 0.4 days, crySI is retained with a mean residence time of 3.0 days; furthermore, fundus photography reveals evidence of retention at two weeks. Unlike the free mini cry, crySI protects the RPE against NaIO 3 challenge for at least two weeks after administration. CrySI also inhibits RPE apoptosis and caspase-3 activation and protects the retina from cell death up to 1-month post NaIO 3 challenge. These results show that intra-ocular ELP-linked peptides such as crySI hold promise as protective agents to prevent RPE atrophy and progressive retinal degeneration in AMD. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular Degeneration (An American Ophthalmological Society Thesis)

PubMed Central

van Kuijk, Frederik J.G.M.; McPherson, Scott W.; Roehrich, Heidi

2017-01-01

Purpose Understanding the apparent paradoxical role of zinc in the pathogenesis and prevention of age-related macular degeneration (AMD) has been limited by the lack of animal models for its detection in sub-retinal epithelial deposits (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1 showed drusen contained high levels of zinc, but the probe was not suitable for in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in drusen. Methods Flat mounts of human sub-RPE tissue using the probes were analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2 (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology. Results Drusen are detected in greater numbers and intensity with ZPP1 compared to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human donor without ocular history, suggesting that ZPP1 might be sensitive enough to detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE deposits at 10 months of age, whereas Zinpyr-1 required 14 months. Conclusion Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1. This enhanced sensitivity will allow for more insightful analysis of zinc in AMD using human specimens and mouse models. This could result in the development of a sensitive in-vivo probe to enhance research on the role zinc in drusen formation and the early clinical diagnosis of AMD. PMID:29021717

Age-related macular degeneration and modification of systemic complement factor H production through liver transplantation.

PubMed

Khandhadia, Samir; Hakobyan, Svetlana; Heng, Ling Z; Gibson, Jane; Adams, David H; Alexander, Graeme J; Gibson, Jonathan M; Martin, Keith R; Menon, Geeta; Nash, Kathryn; Sivaprasad, Sobha; Ennis, Sarah; Cree, Angela J; Morgan, B Paul; Lotery, Andrew J

2013-08-01

To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD). Multicenter, cross-sectional study. We recruited 223 Western European patients ≥ 55 years old who had undergone LT ≥ 5 years previously. We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor). We evaluated AMD status and recipient and donor CFH Y402H genotype. In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014). Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation. The authors have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Predicting taxonomic and functional structure of microbial communities in acid mine drainage

PubMed Central

Kuang, Jialiang; Huang, Linan; He, Zhili; Chen, Linxing; Hua, Zhengshuang; Jia, Pu; Li, Shengjin; Liu, Jun; Li, Jintian; Zhou, Jizhong; Shu, Wensheng

2016-01-01

Predicting the dynamics of community composition and functional attributes responding to environmental changes is an essential goal in community ecology but remains a major challenge, particularly in microbial ecology. Here, by targeting a model system with low species richness, we explore the spatial distribution of taxonomic and functional structure of 40 acid mine drainage (AMD) microbial communities across Southeast China profiled by 16S ribosomal RNA pyrosequencing and a comprehensive microarray (GeoChip). Similar environmentally dependent patterns of dominant microbial lineages and key functional genes were observed regardless of the large-scale geographical isolation. Functional and phylogenetic β-diversities were significantly correlated, whereas functional metabolic potentials were strongly influenced by environmental conditions and community taxonomic structure. Using advanced modeling approaches based on artificial neural networks, we successfully predicted the taxonomic and functional dynamics with significantly higher prediction accuracies of metabolic potentials (average Bray–Curtis similarity 87.8) as compared with relative microbial abundances (similarity 66.8), implying that natural AMD microbial assemblages may be better predicted at the functional genes level rather than at taxonomic level. Furthermore, relative metabolic potentials of genes involved in many key ecological functions (for example, nitrogen and phosphate utilization, metals resistance and stress response) were extrapolated to increase under more acidic and metal-rich conditions, indicating a critical strategy of stress adaptation in these extraordinary communities. Collectively, our findings indicate that natural selection rather than geographic distance has a more crucial role in shaping the taxonomic and functional patterns of AMD microbial community that readily predicted by modeling methods and suggest that the model-based approach is essential to better understand natural acidophilic microbial communities. PMID:26943622

Predicting taxonomic and functional structure of microbial communities in acid mine drainage.

PubMed

Kuang, Jialiang; Huang, Linan; He, Zhili; Chen, Linxing; Hua, Zhengshuang; Jia, Pu; Li, Shengjin; Liu, Jun; Li, Jintian; Zhou, Jizhong; Shu, Wensheng

2016-06-01

Predicting the dynamics of community composition and functional attributes responding to environmental changes is an essential goal in community ecology but remains a major challenge, particularly in microbial ecology. Here, by targeting a model system with low species richness, we explore the spatial distribution of taxonomic and functional structure of 40 acid mine drainage (AMD) microbial communities across Southeast China profiled by 16S ribosomal RNA pyrosequencing and a comprehensive microarray (GeoChip). Similar environmentally dependent patterns of dominant microbial lineages and key functional genes were observed regardless of the large-scale geographical isolation. Functional and phylogenetic β-diversities were significantly correlated, whereas functional metabolic potentials were strongly influenced by environmental conditions and community taxonomic structure. Using advanced modeling approaches based on artificial neural networks, we successfully predicted the taxonomic and functional dynamics with significantly higher prediction accuracies of metabolic potentials (average Bray-Curtis similarity 87.8) as compared with relative microbial abundances (similarity 66.8), implying that natural AMD microbial assemblages may be better predicted at the functional genes level rather than at taxonomic level. Furthermore, relative metabolic potentials of genes involved in many key ecological functions (for example, nitrogen and phosphate utilization, metals resistance and stress response) were extrapolated to increase under more acidic and metal-rich conditions, indicating a critical strategy of stress adaptation in these extraordinary communities. Collectively, our findings indicate that natural selection rather than geographic distance has a more crucial role in shaping the taxonomic and functional patterns of AMD microbial community that readily predicted by modeling methods and suggest that the model-based approach is essential to better understand natural acidophilic microbial communities.

Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

PubMed

Evans, Jennifer R; Lawrenson, John G

2012-06-13

There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). To examine the evidence as to whether or not taking antioxidant vitamin or mineral supplements prevents the development of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 January 2012. We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5 and the other author checked the data entry. We pooled data using a fixed-effect model. We included four RCTs in this review; 62,520 people were included in the analyses. The trials were conducted in Australia, Finland and the USA and investigated vitamin E and beta-carotene supplements. Overall the quality of the evidence was high. People who took these supplements were not at decreased (or increased) risk of developing AMD. The pooled risk ratio for any antioxidant supplement in the prevention of any AMD was 0.98 (95% confidence interval 0.89 to 1.08) and for advanced AMD was 1.05 (95% CI 0.80 to 1.39). Similar results were seen when the analyses were restricted to beta-carotene and alpha-tocopherol alone. There is accumulating evidence that taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. There is no evidence with respect to other antioxidant supplements, such as vitamin C, lutein and zeaxanthin, or any of the commonly marketed multivitamin combinations. Although generally regarded as safe, vitamin supplements may have harmful effects and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane review 'Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration' written by the same review team.

X-82 to Treat Age-related Macular Degeneration

ClinicalTrials.gov

2018-05-30

Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

[Anti-VEGF therapy resistance in neovascular age-related macular degeneration].

PubMed

Budzinskaya, M V; Plyukhova, A A; Sorokin, P A

With account to the increase in the elderly population in most of the developed countries, the WHO defines age-related macular degeneration (AMD) as one of the main causes of blindness in the world. A large percentage of disability is accounted for by exudative, or neovascular, form of AMD. Today, a total of 5 anti-VEGF drugs exist that are recommended for treatment of exudative AMD: pegaptanib, ranibizumab, bevacizumab, aflibercept, and conbercept. Despite significant progress in the treatment of neovascular AMD yielded by the introduction into clinical practice of anti-VEGF drugs, some patients report a lack (down to complete lack) of response with standard treatment patterns and even a decrease in treatment efficacy after repeated intravitreal injections.

Prevention of age-related macular degeneration.

PubMed

Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

2011-02-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

Effects of Ceftiofur and Chlortetracycline on the Resistomes of Feedlot Cattle.

PubMed

Weinroth, Margaret D; Scott, H Morgan; Norby, Bo; Loneragan, Guy H; Noyes, Noelle R; Rovira, Pablo; Doster, Enrique; Yang, Xiang; Woerner, Dale R; Morley, Paul S; Belk, Keith E

2018-07-01

Treatment of food-producing animals with antimicrobial drugs (AMD) is controversial because of concerns regarding promotion of antimicrobial resistance (AMR). To investigate this concern, resistance genes in metagenomic bovine fecal samples during a clinical trial were analyzed to assess the impacts of treatment on beef feedlot cattle resistomes. Four groups of cattle were exposed, using a 2-by-2 factorial design, to different regimens of antimicrobial treatment. Injections of ceftiofur crystalline-free acid (a third-generation cephalosporin) were used to treat all cattle in treatment pens or only a single animal, and either chlortetracycline was included in the feed of all cattle in a pen or the feed was untreated. On days 0 and 26, respectively, pre- and posttrial fecal samples were collected, and resistance genes were characterized using shotgun metagenomics. Treatment with ceftiofur was not associated with changes to β-lactam resistance genes. However, cattle fed chlortetracycline had a significant increase in relative abundance of tetracycline resistance genes. There was also an increase of an AMR class not administered during the study, which is a possible indicator of coselection of resistance genes. Samples analyzed in this study had previously been evaluated by culture characterization ( Escherichia coli and Salmonella ) and quantitative PCR (qPCR) of metagenomic fecal DNA, which allowed comparison of results with this study. In the majority of samples, genes that were selectively enriched through culture and qPCR were not identified through shotgun metagenomic sequencing in this study, suggesting that changes previously documented did not reflect changes affecting the majority of bacterial genetic elements found in the predominant fecal resistome. IMPORTANCE Despite significant concerns about public health implications of AMR in relation to use of AMD in food animals, there are many unknowns about the long- and short-term impact of common uses of AMD for treatment, control, and prevention of disease. Additionally, questions commonly arise regarding how to best measure and quantify AMR genes in relation to public health risks and how to determine which genes are most important. These data provide an introductory view of the utility of using shotgun metagenomic sequencing data as an outcome for clinical trials evaluating the impact of using AMD in food animals. Copyright © 2018 Weinroth et al.

(AMD) ANALYSIS OF AIR QUALITY DATA NEAR ROADWAYS USING A DISPERSION MODEL

EPA Science Inventory

We used a dispersion model to analyze measurements made during a field study conducted by the U.S. EPA in July-August 2006, to estimate the impact of traffic emissions on air quality at distances of tens of meters from an 8 lane highway located in Raleigh, North Carolina. The air...

Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases.

PubMed

Ng, Eugene W M; Adamis, Anthony P

2006-10-01

Vascular endothelial growth factor (VEGF) is a central regulator of both physiological and pathological angiogenesis. Pegaptanib, a 28-nucleotide RNA aptamer specific for the VEGF(165) isoform, binds to it in the extracellular space, leaving other isoforms unaffected, and inhibits such key VEGF actions as promotion of endothelial cell proliferation and survival, and vascular permeability. Pegaptanib already has been examined as a treatment for two diseases associated with ocular neovascularization, age-related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical studies have shown that VEGF(165) alone mediates pathological ocular neovascularization and that its inactivation by pegaptanib inhibits the choroidal neovascularization observed in patients with neovascular AMD. In contrast, physiological vascularization, which is supported by the VEGF(121) isoform, is unaffected by this inactivation of VEGF(165). In addition, animal model studies have shown that intravitreous injection of pegaptanib can inhibit the breakdown of the blood-retinal barrier characteristic of diabetes and even can reverse this damage to some degree. These preclinical findings formed the basis for randomized controlled trials examining the efficacy of pegaptanib as a therapy for AMD and DME. The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial comprising two replicate, pivotal phase 3 studies, demonstrated that intravitreous injection of pegaptanib resulted in significant clinical benefit, compared with sham injection, for all prespecified clinical end points, irrespective of patient demographics or angiographic subtype, and led to pegaptanib's approval as a treatment for AMD. A phase 2 trial has provided support for the efficacy of intravitreous pegaptanib in the treatment of DME.

Optical Coherence Tomography Angiography to Distinguish Changes of Choroidal Neovascularization after Anti-VEGF Therapy: Monthly Loading Dose versus Pro Re Nata Regimen.

PubMed

Miere, Alexandra; Oubraham, Hassiba; Amoroso, Francesca; Butori, Pauline; Astroz, Polina; Semoun, Oudy; Bruyere, Elsa; Pedinielli, Alexandre; Addou-Regnard, Manar; Jung, Camille; Cohen, Salomon Y; Souied, Eric H

2018-01-01

To compare the qualitative and quantitative choroidal neovascularization (CNV) changes after antivascular endothelial growth factor (anti-VEGF) therapy in treatment-naïve and treated eyes with age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). Consecutive patients with neovascular AMD underwent multimodal imaging, including OCTA (AngioPlex, CIRRUS HD-OCT model 5000; Carl Zeiss Meditec, Inc., Dublin, OH) at baseline and at three monthly follow-up visits. Treatment-naive AMD patients undergoing anti-VEGF loading phase were included in group A, while treated patients were included in group B. Qualitative and quantitative OCTA analyses were performed on outer retina to choriocapillaris (ORCC) slab. CNV size was measured using a free image analysis software (ImageJ, open-source imaging processing software, 2.0.0). Twenty-five eyes of 25 patients were enrolled in our study (mean age 78.32 ± 6.8 years): 13 treatment-naïve eyes in group A and 12 treated eyes in group B. While qualitative analysis revealed no significant differences from baseline to follow-up in the two groups, quantitative analysis showed in group A a significant decrease in lesion area ( P = 0.023); in group B, no significant change in the lesion area was observed during anti-VEGF therapy ( P = 0.93). Treatment-naïve and treated eyes with CNV secondary to neovascular AMD respond differently to anti-VEGF therapy. This should be taken into account when using OCTA for CNV follow-up or planning therapeutic strategies.

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging.

PubMed

Zarubina, Anna V; Neely, David C; Clark, Mark E; Huisingh, Carrie E; Samuels, Brian C; Zhang, Yuhua; McGwin, Gerald; Owsley, Cynthia; Curcio, Christine A

2016-05-01

To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Cross-sectional study. A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. Prevalence of SDD in participants with and without AMD. Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume. Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Adherence to a Mediterranean diet, genetic susceptibility, and progression to advanced macular degeneration: a prospective cohort study.

PubMed

Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

2015-11-01

Adherence to a Mediterranean-type diet is linked to a lower risk of mortality and chronic disease, but the association with the progression of age-related macular degeneration (AMD) and genetic susceptibility is unknown. We examined the association of adherence to the Mediterranean diet and genetic susceptibility with progression to advanced AMD. Among 2525 subjects in the AREDS (Age-Related Eye Disease Study), 1028 eyes progressed to advanced AMD over 13 y. Baseline data for demographic and behavioral covariates were collected by using questionnaires. Dietary data were collected from food-frequency questionnaires. The alternate Mediterranean diet (aMeDi) score (range: 0-9) was constructed from individual intakes of vegetables, fruit, legumes, whole grains, nuts, fish, red and processed meats, alcohol, and the ratio of monounsaturated to saturated fats. Ten genetic loci in 7 genes [complement factor H (CFH), age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2/HTRA1), complement component 2 (C2), complement factor B (CFB), complement component 3 (C3), collagen type VIII α 1 (COL8A1), and RAD51 paralog B (RAD51B)] were examined. Survival analysis was used to assess individual eyes for associations between incident AMD and aMeDi score, as well as interaction effects between aMeDi score and genetic variation on risk of AMD. A high aMeDi score (score of 6-9) was significantly associated with a reduced risk of progression to advanced AMD after adjustment for demographic, behavioral, ocular, and genetic covariates (HR: 0.74; 95% CI: 0.61, 0.91; P-trend = 0.007). The aMeDi score was significantly associated with a lower risk of incident advanced AMD among subjects carrying the CFH Y402H nonrisk (T) allele (P-trend = 0.0004, P-interaction = 0.04). The aMeDi score was not associated with AMD among subjects who were homozygous for the risk (C) allele. Higher adherence to a Mediterranean diet was associated with reduced risk of progression to advanced AMD, which may be modified by genetic susceptibility. This trial was registered at clinicaltrials.gov as NCT00594672. © 2015 American Society for Nutrition.

Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging

PubMed Central

Zarubina, Anna V.; Neely, David C.; Clark, Mark E.; Huisingh, Carrie E.; Samuels, Brian C.; Zhang, Yuhua; McGwin, Gerald; Owsley, Cynthia; Curcio, Christine A.

2015-01-01

Purpose To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Design Cross-sectional study. Participants A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Methods Subjects were imaged using spectral domain optical coherence tomography (SD-OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the AREDS 9-step scale. Criteria for SDD presence were identification on ≥1 en-face modality plus SD-OCT or on ≥2 en-face modalities if absent on SD-OCT. SDD were considered present at the person-level if present in 1 or both eyes. Main outcomes measures Prevalence of SDD in participants with and without AMD. Results Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, p =0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (p<0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4x more likely to have AMD than those without SDD (95% CI 2.3–4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD-OCT and confirmed by at least one en-face modality 47% (89/190) were detected exclusively on the ONH SD-OCT volume. Conclusion SDD are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance. PMID:26875000

General Trends of Dihedral Conformational Transitions in a Globular Protein

PubMed Central

Miao, Yinglong; Baudry, Jerome; Smith, Jeremy C.; McCammon, J. Andrew

2017-01-01

Dihedral conformational transitions are analyzed systematically in a model globular protein, cytochrome P450cam, to examine their structural and chemical dependences through combined conventional molecular dynamics (cMD), accelerated molecular dynamics (aMD) and Adaptive Biasing Force (ABF) simulations. The aMD simulations are performed at two acceleration levels, using dihedral and dual boost, respectively. In comparison with cMD, aMD samples protein dihedral transitions ~2 times faster on average using dihedral boost, and ~3.5 times faster using dual boost. In the protein backbone, significantly higher dihedral transition rates are observed in the Bend, Coil and Turn flexible regions, followed by the β bridge and β sheet, and then the helices. Moreover, protein sidechains of greater length exhibit higher transition rates on average in the aMD-enhanced sampling. Sidechains of the same length (particularly Nχ = 2) exhibit decreasing transition rates with residues when going from hydrophobic to polar, then charged and aromatic chemical types. The reduction of dihedral transition rates is found to be correlated with increasing energy barriers as identified through ABF free energy calculations. These general trends of dihedral conformational transitions provide important insights into the hierarchical dynamics and complex free energy landscapes of functional proteins. PMID:26799251

Prevalence of Early and Late Age-Related Macular Degeneration in India: The INDEYE Study

PubMed Central

Krishnan, Tiruvengada; Ravindran, Ravilla D.; Murthy, Gudlavalleti V. S.; Vashist, Praveen; Fitzpatrick, Kathryn E.; Thulasiraj, R. Duraisami; John, Neena; Maraini, Giovanni; Camparini, Monica; Chakravarthy, Usha

2010-01-01

Purpose. To estimate the prevalence of early and late age-related macular degeneration (AMD) in India. Methods. Of 7518 people aged 60 years and older identified from randomly sampled villages in North and South India, 5853 (78%) attended an eye examination including fundus photography. Fundus images were graded according to the Wisconsin Age-Related Maculopathy Grading System. Results. Fundus images were ungradable in 1587 people, mainly because of cataract. People 80 years of age and older were less likely to attend the eye examination and more likely to have ungradable images. For ages 60 to 79 years, the percent prevalence (95% confidence interval [CI]) were late AMD 1.2 (0.8–1.5); and early AMD: grade 1 (soft distinct drusen or pigmentary irregularities), 39.3 (37.2–41.5); grade 2 (soft distinct drusen with pigmentary irregularities or soft indistinct or reticular drusen), 6.7 (5.8–7.6); and grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), 0.2 (0.1–0.4). For ages 80 and older, the respective percent prevalence was: late AMD, 2.5 (0.4–4.7); and early AMD: grade 1, 43.1(35.7–50.6); grade 2, 8.1 (4.3–12.0); and grade 3, 0.5 (0–1.5). Conclusions. The prevalence of early AMD (grades 1 and 2) is similar to that observed in Western populations, but grade 3 appears to be lower. The prevalence of late AMD is comparable to that in Western populations in the age group 60 to 79 years. It is likely that the prevalence in the 80 and older age group is underestimated. PMID:19696177

Clinical features and long-term progression of reticular pseudodrusen in age-related macular degeneration: findings from a multicenter cohort.

PubMed

Gil, J Q; Marques, J P; Hogg, R; Rosina, C; Cachulo, M L; Santos, A; Staurenghi, G; Chakravarthy, U; Silva, R

2017-03-01

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane and the human macula.

PubMed

Del Priore, Lucian V; Tezel, Tongalp H; Kaplan, Henry J

2006-11-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Over the last decade, there have been significant advances in the management of exudative AMD with the introduction of anti-VEGF drugs; however, many patients with exudative AMD continue to lose vision and there are no effective treatments for advanced exudative AMD or geographic atrophy. Initial attempts at macular reconstruction using cellular transplantation have not been effective in reversing vision loss. Herein we discuss the current status of surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We reinforce the concept of maculoplasty for advanced AMD, which is defined as reconstruction of macular anatomy in patients with advanced vision loss. Successful maculoplasty is a three-step process that includes replacing or repairing damaged cells (using transplantation, translocation or stimulation of autologous cell proliferation); immune suppression (if allografts are used to replace damaged cells); and reconstruction or replacement of Bruch's membrane (to restore the integrity of the substrate for proper cell attachment). In the current article we will review the rationale for maculoplasty in advanced AMD, and discuss the results of initial clinical attempts at macular reconstruction. We will then discuss the role of Bruch's membrane damage in limiting transplant survival and visual recovery, and discuss the effects of age-related changes within human Bruch's membrane on the initial attachment and subsequent proliferation of transplanted cells. We will discuss attempts to repair Bruch's membrane by coating with extracellular matrix ligands, anatomic reconstitution of the inner collagen layer, and the effects of Bruch's membrane reconstruction of ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize the importance of continued efforts required for successful maculoplasty.

Efficacy assessment of acid mine drainage treatment with coal mining waste using Allium cepa L. as a bioindicator.

PubMed

Geremias, Reginaldo; Bortolotto, Tiago; Wilhelm-Filho, Danilo; Pedrosa, Rozangela Curi; de Fávere, Valfredo Tadeu

2012-05-01

The aim of this study was to evaluate the efficacy of the treatment of acid mine drainage (AMD) with calcinated coal mining waste using Allium cepa L. as a bioindicator. The pH values and the concentrations of aluminum, iron, manganese, zinc, copper, lead and sulfate were determined before and after the treatment of the AMD with calcinated coal mining waste. Allium cepa L. was exposed to untreated and treated AMD, as well as to mineral water as a negative control (NC). At the end of the exposure period, the inhibition of root growth was measured and the mean effective concentration (EC(50)) was determined. Oxidative stress biomarkers such as lipid peroxidation (TBARS), protein carbonyls (PC), catalase activity (CAT) and reduced glutathione levels (GSH) in the fleshy leaves of the bulb, as well as the DNA damage index (ID) in meristematic cells, were evaluated. The results indicated that the AMD treatment with calcinated coal mining waste resulted in an increase in the pH and an expressive removal of aluminum, iron, manganese and zinc. A high sub-chronic toxicity was observed when Allium cepa L. was exposed to the untreated AMD. However, after the treatment no toxicity was detected. Levels of TBARS and PC, CAT activity and the DNA damage index were significantly increased (P<0.05) in Allium cepa L. exposed to untreated AMD when compared to treated AMD and also to negative controls. No significant alteration in the GSH content was observed. In conclusion, the use of calcinated coal mining waste associated with toxicological tests on Allium cepa L. represents an alternative system for the treatment and biomonitoring of these types of environmental contaminants. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of Age-Related Macular Degeneration on Driving Performance

PubMed Central

Wood, Joanne M.; Black, Alex A.; Mallon, Kerry; Kwan, Anthony S.; Owsley, Cynthia

2018-01-01

Purpose To explore differences in driving performance of older adults with age-related macular degeneration (AMD) and age-matched controls, and to identify the visual determinants of driving performance in this population. Methods Participants included 33 older drivers with AMD (mean age [M] = 76.6 ± 6.1 years; better eye Age-Related Eye Disease Study grades: early [61%] and intermediate [39%]) and 50 age-matched controls (M = 74.6 ± 5.0 years). Visual tests included visual acuity, contrast sensitivity, visual fields, and motion sensitivity. On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist (masked to drivers' visual status). Outcome measures included driving safety ratings (scale of 1–10, where higher values represented safer driving), types of driving behavior errors, locations at which errors were made, and number of critical errors (CE) requiring an instructor intervention. Results Drivers with AMD were rated as less safe than controls (4.8 vs. 6.2; P = 0.012); safety ratings were associated with AMD severity (early: 5.5 versus intermediate: 3.7), even after adjusting for age. Drivers with AMD had higher CE rates than controls (1.42 vs. 0.36, respectively; rate ratio 3.05, 95% confidence interval 1.47–6.36, P = 0.003) and exhibited more observation, lane keeping, and gap selection errors and made more errors at traffic light–controlled intersections (P < 0.05). Only motion sensitivity was significantly associated with driving safety in the AMD drivers (P = 0.005). Conclusions Drivers with early and intermediate AMD can exhibit impairments in their driving performance, particularly during complex driving situations; motion sensitivity was most strongly associated with driving performance. These findings have important implications for assessing the driving ability of older drivers with visual impairment. PMID:29340641

Incidence of Intermediate-stage Age-related Macular Degeneration in Patients With Acquired Immunodeficiency Syndrome.

PubMed

Jabs, Douglas A; Van Natta, Mark L; Pak, Jeong Won; Danis, Ronald P; Hunt, Peter W

2017-07-01

To evaluate the incidence of intermediate-stage age-related macular degeneration (AMD) in patients with acquired immunodeficiency syndrome (AIDS). Cohort study. Patients enrolled in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) underwent 5- and 10-year follow-up retinal photographs. Intermediate-stage AMD (AREDS stage 3) was determined from these photographs by graders at a centralized Reading Center, using the Age-Related Eye Disease Study-2 grading system. The incidence of AMD in LSOCA was compared with that in the Multi-Ethnic Study of Atherosclerosis (MESA), a Human Immunodeficiency Virus (HIV)-uninfected cohort, which used a similar photographic methodology. The incidence of AMD in LSOCA was 0.65/100 person-years (PY). In a multivariate analysis the only significant risk factor for AMD in LSOCA was smoking; the relative risk vs never-smokers was 3.4 for former smokers (95% confidence interval [CI] 1.3, 9.5; P = .02) and 3.3 for current smokers (95% CI 1.1, 9.7; P = .03). Compared with the MESA cohort, the race/ethnicity- and sex-adjusted risk of AMD in LSOCA was 1.75 (95% CI 1.16, 2.64; P = .008), despite the fact that the mean age of the MESA cohort was 17 years greater than the LSOCA cohort (61 ± 9 years vs 44 ± 8 years). Patients with AIDS have a 1.75-fold increased race- and sex-adjusted incidence of intermediate-stage AMD compared with that found in an HIV-uninfected cohort. This increased incidence is consistent with the increased incidence of other age-related diseases in antiretroviral-treated, immune-restored, HIV-infected persons when compared with HIV-uninfected persons. Copyright © 2017 Elsevier Inc. All rights reserved.

Divergence in the lived experience of people with macular degeneration.

PubMed

McCloud, Christine; Khadka, Jyoti; Gilhotra, Jagjit Singh; Pesudovs, Konrad

2014-08-01

The aim of this study was to understand people's experience with age-related macular degeneration (AMD) in light of new treatment successes. An interpretive qualitative methodology was used to facilitate understanding of the experience of people with AMD. Rich in-depth data were collected using focus groups and individual interviews. Thematic analysis of the data occurred through the processes of line-by-line coding, aggregation, and theme development using the NVivo 10 software. A total of 4 focus groups and 16 individual interviews were conducted with 34 people (median age = 81 years; range = 56 to 102 years; 19 females) with AMD. Four major themes arose from the narratives of the participants: cautious optimism, enduring, adaptation, and profound loss. Cautious optimism resonated for participants who had received successful treatment and stabilization of AMD. Enduring emerged as participants with exudative AMD described an ongoing need for invasive and frequent treatments (anti-vascular endothelial growth factor injections) that maintained their vision. Adaptation was evident in the narratives of all participants and was directly related to the physical and psychological limitations that were a consequence of visual disability. Profound loss encompassed both physical and emotional aspects of deteriorating vision and was most evident in patients for whom treatment had failed or had not been considered appropriate for their disease. The findings of this study shed new light on the influence of underlying pathology, disease trajectory, and success of new treatments on quality of life of people living with AMD. Optimism toward maintaining vision in the presence of exudative AMD was described by participants, moderated by ongoing caution and a need for endurance of frequent and often problematic intravitreal treatments. These findings add a deeper understanding of this complex and life-changing experience.

Marginal adaptation of lithium disilicate ceramic crowns cemented with three different resin cements.

PubMed

Peroz, Ingrid; Mitsas, Triantafyllos; Erdelt, Kurt; Kopsahilis, Niko

2018-04-17

The cementation process and cementation materials have an influence on the marginal adaptation of restorations. The gap could be affected by thermal and mechanical loading (TCML). The computerized x-ray microtomography (μCT) method offers the possibility of measuring the marginal gap without destruction of the restoration. The aim of this study was to evaluate the marginal gap (MG) and the absolute marginal discrepancy (AMD) before and after TCML. Thirty-nine human premolars were prepared for full ceramic crowns made of lithium disilicate. The crowns were cemented by three different resins-Panavia F 2.0, Variolink II, and Relyx Unicem. The MG and AMD were evaluated by μCT before and after TCML. Panavia F 2.0 had the lowest MG (before 118 μm-after TMCL 124 μm) and AMD (before 145 μm-after TMCL 154 μm), followed by Relyx Unicem (MG: before 164 μm-after TCML 155 μm; AMD: before 213 μm-after TMCL 209 μm) and Variolink II (MG: before 317 μm-after TMCL 320 μm; AMD: before 412 μm-after TMCL 406 μm). The differences were statistically significant before and after TCML. Rather than TCML, it appeared the resin cement was responsible for differences between the MG and AMD before and after TCML. μCT is an accurate technique for assessing cemented restorations. Panavia F 2.0 has the lowest MG and AMD before and after TCML. The resin material that features a three-step protocol (Variolink II) produced higher MG and AMG values than the Panavia or Relyx Unicem varieties with less or no intermediate steps at all.

Risk Factors for Four-Year Incidence and Progression of Age-Related Macular Degeneration: The Los Angeles Latino Eye Study

PubMed Central

CHOUDHURY, FARZANA; VARMA, ROHIT; MCKEAN-COWDIN, ROBERTA; KLEIN, RONALD; AZEN, STANLEY P.

2011-01-01

PURPOSE To identify risk factors for 4-year incidence and progression of age-related macular degeneration (AMD) in adult Latinos. DESIGN Population-based prospective cohort study. METHODS Participants, aged 40 or older, from The Los Angeles Latino Eye Study (LALES) underwent standardized comprehensive ophthalmologic examinations at baseline and at 4 years of follow-up. Age-related macular degeneration was detected by grading 30-degree stereoscopic fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Multivariate stepwise logistic regression was used to examine the independent association of incidence and progression of AMD and baseline sociodemographic, behavioral, clinical, and ocular characteristics. RESULTS Multivariate analyses revealed that older age (OR per decade of age: 1.52; 95% CI: 1.29, 1.85) and higher pulse pressure (OR per 10 mm Hg: 2.54; 95% CI: 1.36, 4.76) were independently associated with the incidence of any AMD. The same factors were associated with early AMD, soft indistinct drusen, and retinal pigmentary abnormalities. Additionally, presence of clinically diagnosed diabetes mellitus was independently associated with increased retinal pigment (OR: 1.66; 95% CI: 1.01, 2.85), and male gender was associated with retinal pigment epithelial depigmentation (OR 2.50; 95% CI: 1.48, 4.23). Older age (OR per decade of age: 2.20; 95% CI: 1.82, 2.67) and current smoking (OR: 2.85; 95% CI: 1.66, 4.90) were independently associated with progression of AMD. CONCLUSIONS Several modifiable risk factors were associated with 4-year incidence and progression of AMD in Latinos. The results suggest that interventions aimed at reducing pulse pressure and promoting smoking cessation may reduce incidence and progression of AMD, respectively. PMID:21679916

A monoclonal antibody targeting amyloid β (Aβ) restores complement factor I bioactivity: Potential implications in age-related macular degeneration and Alzheimer's disease.

PubMed

Lashkari, Kameran; Teague, Gianna; Chen, Hong; Lin, Yong-Qing; Kumar, Sanjay; McLaughlin, Megan M; López, Francisco J

2018-01-01

Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies. Using this assay, we measured CFI bioactivity in plasma of 194 subjects with AMD, and in samples from subjects with AD that had been treated with GSK933776 as part of the GSK933776 development program in AD. Aβ reduced the CFI bioactivity by 5-fold and pre-incubation with GSK933776 restored CFI bioactivity. In subjects with AMD, plasma CFI levels and bioactivity were not significantly different from non-AMD controls. However, we detected a positive linear trend, suggesting increasing activity with disease severity. In subjects with AD, we observed a 10% and 27% increase in overall CFI bioactivity after treatment with GSK933776 during the second and third dose. Our studies indicate that CFI enzymatic activity can be inhibited by Aβ and be altered in proinflammatory diseases such as AMD and AD, in which deposition of Aβ and activation of the alternative complement cascade are believed to play a key role in the disease process.

Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies

PubMed Central

McKay, Gareth J.; Patterson, Chris C.; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C.; Vingerling, Johannes R.; Ho, Lintje; de Jong, Paulus T.V.M.; Fletcher, Astrid E.; Young, Ian S.; Seland, Johan H.; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vioque, Jesus; Hingorani, Aroon D.; Sofat, Reecha; Dean, Michael; Sawitzke, Julie; Seddon, Johanna M.; Peter, Inga; Webster, Andrew R.; Moore, Anthony T.; Yates, John R.W.; Cipriani, Valentina; Fritsche, Lars G.; Weber, Bernhard H.F.; Keilhauer, Claudia N.; Lotery, Andrew J.; Ennis, Sarah; Klein, Michael L.; Francis, Peter J.; Stambolian, Dwight; Orlin, Anton; Gorin, Michael B.; Weeks, Daniel E.; Kuo, Chia-Ling; Swaroop, Anand; Othman, Mohammad; Kanda, Atsuhiro; Chen, Wei; Abecasis, Goncalo R.; Wright, Alan F.; Hayward, Caroline; Baird, Paul N.; Guymer, Robyn H.; Attia, John; Thakkinstian, Ammarin; Silvestri, Giuliana

2011-01-01

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology. PMID:21882290

Research in Wireless Networks and Communications

DTIC Science & Technology

2008-05-01

TESTBED SETUP AND INITIAL MULTI-HOP EXPERIENCE As a proof of concept, we assembled a testbed platform of nodes based on 400MHz AMD Geode single-board...experi- ments on a testbed network consisting of 400MHz AMD Geode single-board computers made by Thecus Inc. We equipped each of these nodes with two...ground nodes were placed on a line, with about 3 feet of separation between adjacent nodes. The nodes were powered by 400MHz AMD Geode single-board

Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration: a case–control study

PubMed Central

2014-01-01

Background Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients with neovascular AMD. Methods Patients with neovascular AMD and healthy controls were included. Blood samples were obtained and prepared for flow cytometry to investigate the expression of CCR3. Levels of CCL11 were measured in plasma using Cytometric Bead Array. Differences between the groups were tested using Kruskal-Wallis test and Mann–Whitney U test. Results Patients (n = 83) with neovascular AMD and healthy control persons (n = 114) were included in the study. No significant difference in the expression of CCR3 was found on CD9+ granulocytes when comparing patients suffering from neovascular AMD with any of the control groups. We did not find any alteration in CCL11 levels in patients among the age matched groups. There was no correlation between expression of CCR3/CCL11 and clinical response to treatment with anti-vascular endothelial growth factor (VEGF). Conclusion Our results do not suggest a systemic alteration of the CCR3/CCL11 receptor/ligand complex in patients with neovascular AMD. PMID:24575855

Survey on the knowledge of age-related macular degeneration and its risk factors among Singapore residents.

PubMed

Sanjay, Srinivasan; Neo, Hui Yee; Sangtam, Tiakumzuk; Ku, Jae Yee; Chau, Shirley Y M; Rostihar, Abdul Karim; Au Eong, Kah-Guan

2009-11-01

To assess the awareness of age-related macular degeneration (AMD) and its risk factors among Singapore residents. A cross-sectional questionnaire-based telephone survey was conducted to ascertain the awareness of AMD with regards to knowledge of the disease entity and possible risk factors among Singapore residents. A Singapore residential telephone directory was used to identify potential households by choosing the first and last entries on randomly selected pages. Respondents included individuals from households with landline telephone connection who were willing to participate in the study after a brief introduction about the study. Verbal consent was sought before proceeding with the interview. Interpreters were used for respondents whose ability to converse in English was limited. Prior to commencement of the study, the protocol was reviewed and approved by Ethics committee of the Domain Specific Review Board. The interviewers contacted 796 subjects from different households, of which 520 participated (response rate, 65.3%). The age of the respondents ranged from 18 to 85 (median 41) years. Only 38 (7.3%) of them were aware of AMD, the majority of whom had completed secondary or higher education. Two hundred (38.5%) and 191 (36.7%) of the respondents considered age and smoking, respectively, to be risk factors for AMD. The awareness of AMD among Singapore residents is low. AMD awareness needs to be improved by educational programmes designed for this specific purpose.

Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration: a case-control study.

PubMed

Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten; Nissen, Mogens Holst; Hviid, Thomas; Sørensen, Torben Lykke

2014-02-27

Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients with neovascular AMD. Patients with neovascular AMD and healthy controls were included. Blood samples were obtained and prepared for flow cytometry to investigate the expression of CCR3. Levels of CCL11 were measured in plasma using Cytometric Bead Array. Differences between the groups were tested using Kruskal-Wallis test and Mann-Whitney U test. Patients (n = 83) with neovascular AMD and healthy control persons (n = 114) were included in the study. No significant difference in the expression of CCR3 was found on CD9+ granulocytes when comparing patients suffering from neovascular AMD with any of the control groups. We did not find any alteration in CCL11 levels in patients among the age matched groups. There was no correlation between expression of CCR3/CCL11 and clinical response to treatment with anti-vascular endothelial growth factor (VEGF). Our results do not suggest a systemic alteration of the CCR3/CCL11 receptor/ligand complex in patients with neovascular AMD.

Bacterial, archaeal, and fungal community responses to acid mine drainage-laden pollution in a rice paddy soil ecosystem.

PubMed

Wang, Han; Zeng, Yufei; Guo, Chuling; Bao, Yanping; Lu, Guining; Reinfelder, John R; Dang, Zhi

2018-03-01

Lacking sufficient clean water, the paddy soils along the Hengshi River have suffered from long-term acid mine drainage (AMD) contamination. The impacted cropland is too heavily contaminated to grow food safely. The microbial communities inhabiting the environment play pivotal roles in the crop growth, health, and ecological services. In this study, the bacterial, archaeal, and fungal communities in the impacted paddy soil were examined using high-throughput Illumina MiSeq sequencing. The results showed that AMD irrigation considerably enriched the bacterial phylum Acidobacteria and the archaeal phylum Crenarchaeota, while the fungal community was more stable. The abundances of Acidobacteria and Crenarchaeota were significantly positively correlated with the AMD-related environmental factors of pH and heavy metals (Cu, Pb, and Zn). In the most contaminated samples, communities were dominated by the bacteria Candidatus Solibacter and Candidatus Koribacter from the Acidobacteria family. Functional gene profile analysis demonstrated that the energy metabolic processes of the microbial communities, especially C/N related pathways, have adjusted and are well-adapted to tolerating AMD contamination. The present study described the structural and functional differentiation of microbial communities in the rice paddy soil under AMD irrigation. The results are useful for the development of bioremediation strategies using native microbes in the cleanup and biorestoration of AMD-contaminated agriculture soil. Copyright © 2017 Elsevier B.V. All rights reserved.

Remediation of AMD using industrial waste adsorbents

NASA Astrophysics Data System (ADS)

Mohammed, Nuur Hani Bte; Yaacob, Wan Zuhairi Wan

2016-11-01

The study investigates the characteristic of industrial waste as adsorbents and its potential as heavy metals absorbents in AMD samples. The AMD sample was collected from active mine pond and the pH was measured in situ. The metal contents were analyzed by ICP-MS. The AMD water was very acidic (pH< 3.5), and the average heavy metals content in AMD were high especially in Fe (822.029 mg/l). Fly ash was found to be the most effective absorbent material containing high percentage of CaO (57.24%) and SiO2 (13.88%), followed by ladle furnace slag containing of high amount of CaO (51.52%) and Al2O3 (21.23%), while biomass ash consists of SiO2 (43.07%) and CaO (12.97%). Tank analysis display a huge changes due to pH value change from acidity to nearly neutral phases. After 50 days, fly ash remediation successfully increase the AMD pH values from pH 2.57-7.09, while slag change from acidity to nearly alkaline phase from pH 2.60-7.3 and biomass has change to pH 2.54-6.8. Fly ash has successfully remove Fe, Mn, Cu, and Ni. Meanwhile, slag sample displays as an effective adsorbent to adsorb more Pb and Cd in acid mine drainage.

Health State Utility Values for Age-Related Macular Degeneration: Review and Advice.

PubMed

Butt, Thomas; Tufail, Adnan; Rubin, Gary

2017-02-01

Health state utility values are a major source of uncertainty in economic evaluations of interventions for age-related macular degeneration (AMD). This review identifies and critiques published utility values and methods for eliciting de novo utility values in AMD. We describe how utility values have been used in healthcare decision making and provide guidance on the choice of utility values for future economic evaluations for AMD. Literature was searched using PubMed, and health technology assessments (HTA) were searched using HTA agency websites to identify articles reporting utility values or approaches to derive utility values in AMD and articles applying utilities for use in healthcare decision making relating to treatments for AMD. A total of 70 studies qualified for data extraction, 22 of which were classified as containing utility values and/or elicitation methods, and 48 were classified as using utility values in decision making. A large number of studies have elicited utility values for AMD, although those applied to decision making have focused on a few of these. There is an appreciation of the challenges in the measurement and valuation of health states, with recent studies addressing challenges such as the insensitivity of generic health-related quality of life (HRQoL) questionnaires and utility in the worse-seeing eye. We would encourage careful consideration when choosing utility values in decision making and an explicit critique of their applicability to the decision problem.

Automated age-related macular degeneration classification in OCT using unsupervised feature learning

NASA Astrophysics Data System (ADS)

Venhuizen, Freerk G.; van Ginneken, Bram; Bloemen, Bart; van Grinsven, Mark J. J. P.; Philipsen, Rick; Hoyng, Carel; Theelen, Thomas; Sánchez, Clara I.

2015-03-01

Age-related Macular Degeneration (AMD) is a common eye disorder with high prevalence in elderly people. The disease mainly affects the central part of the retina, and could ultimately lead to permanent vision loss. Optical Coherence Tomography (OCT) is becoming the standard imaging modality in diagnosis of AMD and the assessment of its progression. However, the evaluation of the obtained volumetric scan is time consuming, expensive and the signs of early AMD are easy to miss. In this paper we propose a classification method to automatically distinguish AMD patients from healthy subjects with high accuracy. The method is based on an unsupervised feature learning approach, and processes the complete image without the need for an accurate pre-segmentation of the retina. The method can be divided in two steps: an unsupervised clustering stage that extracts a set of small descriptive image patches from the training data, and a supervised training stage that uses these patches to create a patch occurrence histogram for every image on which a random forest classifier is trained. Experiments using 384 volume scans show that the proposed method is capable of identifying AMD patients with high accuracy, obtaining an area under the Receiver Operating Curve of 0:984. Our method allows for a quick and reliable assessment of the presence of AMD pathology in OCT volume scans without the need for accurate layer segmentation algorithms.

[Coping with wet age-related macular degeneration--a study from Switzerland].

PubMed

Hüsler, S; Schmid, H

2013-12-01

Age-related macular degeneration (AMD) affects the quality of life of about 40,000 patients in Switzerland. The treatment of wet AMD with intravitreal injected anti-vascular endothelial growth factor (VEGF) can be a heavy burden for many patients. The aim of this study was to understand the quality of life of the patients and to seek ways to improve the treatment compliance. Half-structured telephone interviews with 28 patients between 56 and 94 years of age were transcribed and analysed. In 21 patients, both eyes were concerned with AMD. The quality of life of patients with AMD is reduced. Many activities of daily living are hindered. Dependence on others increases. Communication of the diagnosis is perceived as a shock. Most interviewees wish for more information about their specific situation. Auxiliary means and counselling possibilities are hardly known. Wet AMD impacts on the quality of life of the patient. Treatment should therefore not be limited to the medical treatment of the ill eye. Triage to rehabilitation and counselling services should be included as important duties of the medical practitioners. Georg Thieme Verlag KG Stuttgart · New York.