Science.gov

Sample records for macular pigment levels

  1. [Macular pigments].

    PubMed

    Canovas, Renata; Cypel, Marcela; Farah, Michel Eid; Belfort, Rubens

    2009-01-01

    Lutein and Zeaxanthin are yellow pigments located at the macula. Because of your location macular pigments decrease and filter the amount of blue light that reach photoreceptors, protect the outer retina from oxidative stress and may improve the vision quality. This is a review regarding incorporation mechanism, function and knowledge update. PMID:20098912

  2. Macular pigment assessment by motion photometry.

    PubMed

    Moreland, J D

    2004-10-15

    A Moreland anomaloscope was modified to measure macular pigment optical density (MPOD) profiles by motion photometry. A grating (spatial frequency 0.38 c deg(-1)), whose alternate bars were filled, respectively, with 460 nm (maximum MP absorption) and 580 nm (zero MP absorption) lights, drifted steadily at 37 degrees s(-1). The subject adjusted the 580 nm radiance to minimise perceived motion (equiluminance between 460 and 580 nm). Five or more settings were made for two foveal fields (0.9 degrees and 2.2 degrees diameter) and 11 extrafoveal annular fields (0.8 degrees -7.5 degrees eccentricity). Twenty subjects made measurements for both eyes: some with replications. MPOD profiles varied in scale (0.18-0.75 for the 0.9 degrees foveal field) and in shape. A mean profile was derived. Foveal data were optimally aligned with annular data in that profile when plotted at 0.71 of the foveal field radius. Factors that limit precision were identified, such as fixation errors foveally and Troxler's effect parafoveally.

  3. Measurement of macular pigment optical density in a healthy chinese population sample

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macular pigment may protect against age-related macular degeneration (AMD) by its capability to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasians populations. The purpose of this study was to assess macular ...

  4. Idiopathic eruptive macular pigmentation with papillomatosis (IEMPP): A controversial entity.

    PubMed

    Pang, Y Z; Koh, W L; Ang, C C

    2016-01-01

    A 19-year-old man with a 6-month history of progressive development of hyperpigmented, velvety plaques on the face and body. A diagnosis of idiopathic eruptive macular pigmentation with papillomatosis (IEMPP) was determined. This entity is discussed. PMID:27617467

  5. The relationship between foveal short-wavelength-sensitive visual function and macular pigment optical density in the ageing age.

    PubMed

    Beirne, Raymond O

    2013-06-28

    To investigate the role of macular pigment in preserving foveal short-wavelength-sensitive (SWS) visual function in the ageing eye orientation identification acuity was measured in the fovea and at 12° eccentricity (nasal visual field) under SWS-cone isolating conditions in 73 participants (aged 20-71). Macular pigment optical density (MPOD) was measured at 0.5° eccentricity from the foveal centre using a heterochromatic flicker photometry (HFP) based instrument. MPOD was not significantly related to age but reduced SWS orientation identification acuity was associated with increasing age in the fovea and at 12° eccentricity. The rate at which foveal acuity changed in relation to acuity at 12° with increasing age was not significantly related to macular pigment levels. These findings do not support the hypothesis that higher macular pigment levels protect S-cone mediated foveal visual function in the ageing eye. PMID:23591086

  6. Historic perspectives. Macular yellow pigment. The first 200 years.

    PubMed

    Nussbaum, J J; Pruett, R C; Delori, F C

    1981-01-01

    Since 1782 there has been continuing controversy concerning the curious central coloration referred to as "macular yellow," but no cumulative source of information on the subject exists. This paper reviews the research efforts of two centuries to determine the existence, nature, location, and function of a specialized pigment in the foveal region. Using white-light illumination, it is difficult to see a macular yellow spot in the living eye; it is best observed and documented by red-free ophthalmoscopy and blue-light monochromatic photography. Histologic, biochemical, and spectral absorption data suggest that the yellow color is due to a xanthophyllic pigment, lutein, that is distributed in all retinal layers internal to the outer nuclear layer, with greatest concentration in the outer and inner plexiform layers. Clinically absent in newborns, the pigment gradually accumulates from dietary sources and appears to serve both as an optical filter, by absorbing blue light and reducing chromatic aberration, and in a protective capacity, preventing actinic damage. The absorption characteristics of the yellow pigment contribute to the central dark spot seen during fluorescein angiography and to the risk of photocoagulation near the fovea. Its apparent absence in albinos and the reported functional improvement in certain degenerative retinopathies following supplemental xanthophyll administration suggest a possible role in hereditary or acquired maculopathies. PMID:6758089

  7. Historic perspectives. Macular yellow pigment. The first 200 years.

    PubMed

    Nussbaum, J J; Pruett, R C; Delori, F C

    1981-01-01

    Since 1782 there has been continuing controversy concerning the curious central coloration referred to as "macular yellow," but no cumulative source of information on the subject exists. This paper reviews the research efforts of two centuries to determine the existence, nature, location, and function of a specialized pigment in the foveal region. Using white-light illumination, it is difficult to see a macular yellow spot in the living eye; it is best observed and documented by red-free ophthalmoscopy and blue-light monochromatic photography. Histologic, biochemical, and spectral absorption data suggest that the yellow color is due to a xanthophyllic pigment, lutein, that is distributed in all retinal layers internal to the outer nuclear layer, with greatest concentration in the outer and inner plexiform layers. Clinically absent in newborns, the pigment gradually accumulates from dietary sources and appears to serve both as an optical filter, by absorbing blue light and reducing chromatic aberration, and in a protective capacity, preventing actinic damage. The absorption characteristics of the yellow pigment contribute to the central dark spot seen during fluorescein angiography and to the risk of photocoagulation near the fovea. Its apparent absence in albinos and the reported functional improvement in certain degenerative retinopathies following supplemental xanthophyll administration suggest a possible role in hereditary or acquired maculopathies.

  8. Structure and Conformation of the Carotenoids in Human Retinal Macular Pigment.

    PubMed

    Arteni, Ana-Andreea; Fradot, Mathias; Galzerano, Denise; Mendes-Pinto, Maria M; Sahel, José-Alain; Picaud, Serge; Robert, Bruno; Pascal, Andrew A

    2015-01-01

    Human retinal macular pigment (MP) is formed by the carotenoids lutein and zeaxanthin (including the isomer meso-zeaxanthin). MP has several functions in improving visual performance and protecting against the damaging effects of light, and MP levels are used as a proxy for macular health-specifically, to predict the likelihood of developing age-related macular degeneration. While the roles of these carotenoids in retinal health have been the object of intense study in recent years, precise mechanistic details of their protective action remain elusive. We have measured the Raman signals originating from MP carotenoids in ex vivo human retinal tissue, in order to assess their structure and conformation. We show that it is possible to distinguish between lutein and zeaxanthin, by their excitation profile (related to their absorption spectra) and the position of their ν1 Raman mode. In addition, analysis of the ν4 Raman band indicates that these carotenoids are present in a specific, constrained conformation in situ, consistent with their binding to specific proteins as postulated in the literature. We discuss how these conclusions relate to the function of these pigments in macular protection. We also address the possibilities for a more accurate, consistent measurement of MP levels by Raman spectroscopy.

  9. Structure and Conformation of the Carotenoids in Human Retinal Macular Pigment

    PubMed Central

    Arteni, Ana-Andreea; Fradot, Mathias; Galzerano, Denise; Mendes-Pinto, Maria M.; Sahel, José-Alain; Picaud, Serge; Robert, Bruno; Pascal, Andrew A.

    2015-01-01

    Human retinal macular pigment (MP) is formed by the carotenoids lutein and zeaxanthin (including the isomer meso-zeaxanthin). MP has several functions in improving visual performance and protecting against the damaging effects of light, and MP levels are used as a proxy for macular health–specifically, to predict the likelihood of developing age-related macular degeneration. While the roles of these carotenoids in retinal health have been the object of intense study in recent years, precise mechanistic details of their protective action remain elusive. We have measured the Raman signals originating from MP carotenoids in ex vivo human retinal tissue, in order to assess their structure and conformation. We show that it is possible to distinguish between lutein and zeaxanthin, by their excitation profile (related to their absorption spectra) and the position of their ν1 Raman mode. In addition, analysis of the ν4 Raman band indicates that these carotenoids are present in a specific, constrained conformation in situ, consistent with their binding to specific proteins as postulated in the literature. We discuss how these conclusions relate to the function of these pigments in macular protection. We also address the possibilities for a more accurate, consistent measurement of MP levels by Raman spectroscopy. PMID:26313550

  10. Macular pigment and lens optical density measurements-evaluating a flicker machine with novel features

    NASA Astrophysics Data System (ADS)

    Mukherjee, Anirbaan

    Age related macular degeneration (AMD) is one of the leading causes of blindness amongst the elderly. Macular pigment (MP) in the retina has been established to protect individuals against AMD. Improving levels of MP by diet or supplements is the constant quest of clinical practitioners and researchers, thus necessitating development of instruments capable of repeatable and reliable MP measurement. Cataract, a consequence of the rising opacity levels of the lens with age is one of the other major causes of blindness in the world. Mapcatsf, a LED-based microprocessor-controlled heterochromatic flicker photometer (HFP) using photopic vision is capable of measuring the levels of MP and the opacity of the lens in terms of optical density. Test-retest measurements conducted on 83 subjects were analyzed for repeatability in macular pigment optical density (MPOD) measurements. Reliability of the lens optical density (LOD) measurements were tested and compared with those obtained at absolute scotopic thresholds for 25 individuals. A supplement study with 32 individuals both in the young (50) age groups for 6 months further established Mapcatsf's capacity to monitor changing levels of MP in individuals. As an overall outcome, high levels of repeatability and reliability were obtained in MPOD and LOD measurements establishing Mapcatsf as an instrument for use in clinical settings in the future.

  11. Macular pigment density measured by autofluorescence spectrometry: comparison with reflectometry and heterochromatic flicker photometry.

    PubMed

    Delori, F C; Goger, D G; Hammond, B R; Snodderly, D M; Burns, S A

    2001-06-01

    We present a technique for estimating the density of the human macular pigment noninvasively that takes advantage of the autofluorescence of lipofuscin, which is normally present in the human retinal pigment epithelium. By measuring the intensity of fluorescence at 710 nm, where macular pigment has essentially zero absorption, and stimulating the fluorescence with two wavelengths, one well absorbed by macular pigment and the other minimally absorbed by macular pigment, we can make accurate single-pass measurements of the macular pigment density. We used the technique to measure macular pigment density in a group of 159 subjects with normal retinal status ranging in age between 15 and 80 years. Average macular pigment density was 0.48 +/- 0.16 density unit (D.U.) for a 2 degrees -diameter test field. We show that these estimates are highly correlated with reflectometric (mean: 0.23 +/- 0.07 D.U.) and psychophysical (mean: 0.37 +/- 0.26 D.U.; obtained by heterochromatic flicker photometry) estimates of macular pigment in the same subjects, despite the fact that systematic differences in the estimated density exist between techniques. Repeat measurements over both short- and long-time intervals indicate that the autofluorescence technique is reproducible: The mean absolute difference between estimates was less than 0.05 D.U., superior to the reproducibility obtained by reflectometry and flicker photometry. To understand the systematic differences between density estimates obtained from the different methods, we analyzed the underlying assumptions of each technique. Specifically, we looked at the effect of self-screening by visual pigment, the effect of changes in optical property of the deeper retinal layers, including the role of retinal pigmented epithelium melanin, and the role of secondary fluorophores and reflectors in the anterior layers of the retina.

  12. Macular pigment and the edge hypothesis of flicker photometry.

    PubMed

    Bone, Richard A; Landrum, John T; Gibert, Jorge C

    2004-12-01

    Heterochromatic flicker photometry is commonly used to measure macular pigment optical density (MPOD) in the human retina. It has been proposed, and accepted by many, that the MPOD so measured represents the value at a retinal location corresponding to the edge of the flickering, circular stimulus. We have investigated this proposal by using a series of annular stimuli to determine the MPOD distribution in the central 1.5 degrees of the retina for both eyes of 10 subjects. The MPOD obtained using a 1.5 degrees circular stimulus matched the MPOD distribution at a retinal eccentricity that was always less than the stimulus radius, and averaged, for the 10 subjects, 51% of the stimulus radius. Similar results were obtained using a 1 degrees stimulus. Thus the edge hypothesis is inconsistent with our data. We suggest that involuntary eye movements may be responsible for an apparent edge effect.

  13. Macular pigment optical density is related to serum lutein in retinitis pigmentosa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: To determine whether macular pigment optical density (MPOD) is related to the degree of cystoid macular edema (CME) in patients with retinitis pigmentosa. Methods: We measured MPOD with heterochromatic flicker photometry and central foveal retinal thickness with optical coherence tomography...

  14. Idiopathic eruptive macular pigmentation in a child with citrin deficiency.

    PubMed

    Fu, Chu-Li; Hu, Yun-Feng; Song, Yuan-Zong

    2016-09-01

    Idiopathic eruptive macular pigmentation (IEMP) is a rare dermatological disorder with generally unclear etiology and pathogenesis. A 5½-year-old girl was referred to hospital with a 10 month history of brown skin rashes. In early infancy, citrin deficiency had been diagnosed with the SLC25A13 genotype c.851_854del4/c.998G > A, but all clinical and laboratory abnormalities recovered following the introduction of a lactose-free and medium-chain triglyceride-enriched formula. Physical examination at referral indicated symmetric, multiple and non-scaly brown macules on the neck, trunk, buttocks and proximal parts of the extremities. Histopathology indicated epidermal basal layer hyperpigmentation with an irregular distribution, along with a large number of melanophages in the upper dermis. The diagnosis of IEMP was thus made. Within 2 years of follow up, the rashes disappeared spontaneously and gradually. To our knowledge, this is the first description of IEMP in a patient with silent citrin deficiency. PMID:27389718

  15. Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions

    PubMed Central

    Sharifzadeh, Mohsen; Bernstein, Paul S.; Gellermann, Werner

    2011-01-01

    We have developed a CCD-camera-based nonmydriatic instrument that detects fluorescence from retinal lipofuscin chromophores (“autofluorescence”) as a means to indirectly quantify and spatially image the distribution of macular pigment (MP). The lipofuscin fluorescence intensity is reduced at all retinal locations containing MP, since MP has a competing absorption in the blue–green wavelength region. Projecting a large diameter, 488 nm excitation spot onto the retina, centered on the fovea, but extending into the macular periphery, and comparing lipofuscin fluorescence intensities outside and inside the foveal area, it is possible to spatially map out the distribution of MP. Spectrally selective detection of the lipofuscin fluorescence reveals an important wavelength dependence of the obtainable image contrast and deduced MP optical density levels, showing that it is important to block out interfering fluorescence contributions in the detection setup originating from ocular media such as the lens. Measuring 70 healthy human volunteer subjects with no ocular pathologies, we find widely varying spatial extent of MP, distinctly differing distribution patterns of MP, and strongly differing absolute MP levels among individuals. Our population study suggests that MP imaging based on lipofuscin fluorescence is useful as a relatively simple, objective, and quantitative noninvasive optical technique suitable to rapidly screen MP levels and distributions in healthy humans with undilated pupils. PMID:16985523

  16. Bimodal spatial distribution of macular pigment: evidence of a gender relationship

    NASA Astrophysics Data System (ADS)

    Delori, François C.; Goger, Douglas G.; Keilhauer, Claudia; Salvetti, Paola; Staurenghi, Giovanni

    2006-03-01

    The spatial distribution of the optical density of the human macular pigment measured by two-wavelength autofluorescence imaging exhibits in over half of the subjects an annulus of higher density superimposed on a central exponential-like distribution. This annulus is located at about 0.7° from the fovea. Women have broader distributions than men, and they are more likely to exhibit this bimodal distribution. Maxwell's spot reported by subjects matches the measured distribution of their pigment. Evidence that the shape of the foveal depression may be gender related leads us to hypothesize that differences in macular pigment distribution are related to anatomical differences in the shape of the foveal depression.

  17. Autofluorescence imaging of macular pigment: influence and correction of ocular media opacities

    NASA Astrophysics Data System (ADS)

    Sharifzadeh, Mohsen; Obana, Akira; Gohto, Yuko; Seto, Takahiko; Gellermann, Werner

    2014-09-01

    The healthy adult human retina contains in its macular region a high concentration of blue-light absorbing carotenoid compounds, known as macular pigment (MP). Consisting of the carotenoids lutein, zeaxanthin, and meso-zeaxanthin, the MP is thought to shield the vulnerable tissue layers in the retina from light-induced damage through its function as an optical attenuator and to protect the tissue cells within its immediate vicinity through its function as a potent antioxidant. Autofluorescence imaging (AFI) is emerging as a viable optical method for MP screening of large subject populations, for tracking of MP changes over time, and for monitoring MP uptake in response to dietary supplementation. To investigate the influence of ocular media opacities on AFI-based MP measurements, in particular, the influence of lens cataracts, we conducted a clinical trial with a large subject population (93 subjects) measured before and after cataract surgery. General AFI image contrast, retinal blood vessel contrast, and presurgery lens opacity scores [Lens Opacities Classification System III (LOCS III)] were investigated as potential predictors for image degradation. These clinical results show that lens cataracts can severely degrade the achievable pixel contrasts in the AFI images, which results in nominal MP optical density levels that are artifactually reduced. While LOCS III scores and blood vessel contrast are found to be only a weak predictor for this effect, a strong correlation exists between the reduction factor and the image contrast, which can be quantified via pixel intensity histogram parameters. Choosing the base width of the histogram, the presence or absence of ocular media opacities can be determined and, if needed, the nominal MP levels can be corrected with factors depending on the strength of the opacity.

  18. Lutein, Zeaxanthin and Meso-zeaxanthin Supplementation Associated with Macular Pigment Optical Density

    PubMed Central

    Ma, Le; Liu, Rong; Du, Jun Hui; Liu, Tao; Wu, Shan Shan; Liu, Xiao Hong

    2016-01-01

    The purpose of this study was to evaluate the effects of lutein, zeaxanthin and meso-zeaxanthin on macular pigment optical density (MPOD) in randomized controlled trials (RCTs) among patients with age-related macular degeneration (AMD) and healthy subjects. Medline, Embase, Web of Science and Cochrane Library databases was searched through May 2016. Meta-analysis was conducted to obtain adjusted weighted mean differences (WMD) for intervention-versus-placebo group about the change of MPOD between baseline and terminal point. Pearson correlation analysis was used to determine the relationship between the changes in MPOD and blood xanthophyll carotenoids or baseline MPOD levels. Twenty RCTs involving 938 AMD patients and 826 healthy subjects were identified. Xanthophyll carotenoids supplementation was associated with significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14). Stratified analysis showed a greater increase in MPOD among trials supplemented and combined with meso-zeaxanthin. Additionally, the changes in MPOD were related with baseline MPOD levels (rAMD = −0.43, p = 0.06; rhealthy subjects = −0.71, p < 0.001) and blood xanthophyll carotenoids concentration (rAMD = 0.40, p = 0.07; rhealthy subjects = 0.33, p = 0.05). This meta-analysis revealed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects with a dose-response relationship. PMID:27420092

  19. Lutein, Zeaxanthin and Meso-zeaxanthin Supplementation Associated with Macular Pigment Optical Density.

    PubMed

    Ma, Le; Liu, Rong; Du, Jun Hui; Liu, Tao; Wu, Shan Shan; Liu, Xiao Hong

    2016-01-01

    The purpose of this study was to evaluate the effects of lutein, zeaxanthin and meso-zeaxanthin on macular pigment optical density (MPOD) in randomized controlled trials (RCTs) among patients with age-related macular degeneration (AMD) and healthy subjects. Medline, Embase, Web of Science and Cochrane Library databases was searched through May 2016. Meta-analysis was conducted to obtain adjusted weighted mean differences (WMD) for intervention-versus-placebo group about the change of MPOD between baseline and terminal point. Pearson correlation analysis was used to determine the relationship between the changes in MPOD and blood xanthophyll carotenoids or baseline MPOD levels. Twenty RCTs involving 938 AMD patients and 826 healthy subjects were identified. Xanthophyll carotenoids supplementation was associated with significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14). Stratified analysis showed a greater increase in MPOD among trials supplemented and combined with meso-zeaxanthin. Additionally, the changes in MPOD were related with baseline MPOD levels (rAMD = -0.43, p = 0.06; rhealthy subjects = -0.71, p < 0.001) and blood xanthophyll carotenoids concentration (rAMD = 0.40, p = 0.07; rhealthy subjects = 0.33, p = 0.05). This meta-analysis revealed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects with a dose-response relationship. PMID:27420092

  20. Macular pigmentation complicating irritant contact dermatitis and viral warts in Laugier-Hunziker syndrome.

    PubMed

    Bhoyrul, B; Paulus, J

    2016-04-01

    Laugier-Hunziker syndrome (LHS) is a rare acquired disorder characterized by macu-lar pigmentation of the lips and oral mucosa, with frequent longitudinal melanonychia. Involvement of other areas, such as the genitalia and fingers, has rarely been described. LHS is a benign condition with no known systemic manifestations. We report the case of a woman who developed melanotic macules on her fingers and elbow 16 years after the onset of pigmentation of her lips. This unusual feature of LHS in our patient was associated with irritant contact dermatitis and viral warts. Only two cases of an association with an inflammatory dermatosis have been reported previously in the literature.

  1. Measurement of macular pigment optical density among healthy Chinese people and patients with early-stage age-related macular degeneration

    PubMed Central

    Ren, Xue-Tao; Gu, Hong; Han, Xu; Zhang, Jun-Yan; Li, Xue; Yang, Xiu-Fen; Xu, Jun; Snellingen, Torkel; Liu, Xi-Pu; Wang, Ning-Li; Liu, Ning-Pu

    2015-01-01

    AIM To measure the macular pigment optical density (MPOD) in healthy Chinese people and patients with early age-related macular degeneration (AMD). METHODS Cross-sectional population based study. Demographic and lifestyle characteristics were ascertained by questionnaire. A food frequency questionnaire was completed for all participants. Participants underwent general physical and ophthalmic examinations and MPOD was measured by heterochromatic flicker photometry. Foveal architecture was measured by optical coherence tomography. RESULTS MPOD of 225 participants (122 healthy and 103 early AMD) was 0.48±0.18. Patients with early AMD (0.52±0.19) tended to have higher MPOD levels than healthy people (0.47±0.17), but the difference was not statistically significant (P=0.06). Participants with carrot or corn oil intake every week tended to have higher levels of MPOD (P=0.002 and 0.008 respectively) while those with corn intake had relatively lower level of MPOD (P=0.01). MPOD increased with the center foveal thickness (P=0.01). CONCLUSION Our findings show that there is no statistically significant association between MPOD and early AMD in the studied population. MPOD is related to center foveal thickness and diets would influence MPOD levels. PMID:26682171

  2. The Effect of Modified Eggs and an Egg-Yolk Based Beverage on Serum Lutein and Zeaxanthin Concentrations and Macular Pigment Optical Density: Results from a Randomized Trial

    PubMed Central

    Kelly, Elton R.; Plat, Jogchum; Haenen, Guido R. M. M.; Kijlstra, Aize; Berendschot, Tos T. J. M.

    2014-01-01

    Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the progression of age-related macular degeneration. The aim of this study was to investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations and macular pigment levels. Naturally enriched eggs were made by increasing the levels of the xanthophylls lutein and zeaxanthin in the feed given to laying hens. One hundred healthy volunteers were recruited and randomized into 5 groups for 90 days. Group one added one normal egg to their daily diet and group two received a lutein enriched egg-yolk based beverage. Group three added one lutein enriched egg and group four one zeaxanthin enriched egg to their diet. Group five was the control group and individuals in this group did not modify their daily diet. Serum lutein and zeaxanthin concentrations and macular pigment densities were obtained at baseline, day 45 and day 90. Macular pigment density was measured by heterochromatic flicker photometry. Serum lutein concentration in the lutein enriched egg and egg yolk-based beverage groups increased significantly (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration was observed in individuals receiving zeaxanthin enriched eggs (P< 0.001, 430%). No changes were observed in macular pigment density in the various groups tested. The results indicate that daily consumption of lutein or zeaxanthin enriched egg yolks as well as an egg yolk-based beverage show increases in serum lutein and zeaxanthin levels that are comparable with a daily use of 5 mg supplements. Trial Registration ClinicalTrials.gov NCT00527553 PMID:24675775

  3. Macular pigment and its contribution to visual performance and experience

    PubMed Central

    Loughman, James; Davison, Peter A.; Nolan, John M.; Akkali, Mukunda C.; Beatty, Stephen

    2010-01-01

    There is now a consensus, based on histological, biochemical and spectral absorption data, that the yellow colour observed at the macula lutea is a consequence of the selective accumulation of dietary xanthophylls in the central retina of the living eye. Scientific research continues to explore the function(s) of MP in the human retina, with two main hypotheses premised on its putative capacity to (1) protect the retina from (photo)-oxidative damage by means of its optical filtration and/or antioxidant properties, the so-called protective hypothesis and (2) influence the quality of visual performance by means of selective short wavelength light absorption prior to photoreceptor light capture, thereby attenuating the effects of chromatic aberration and light scatter, the so-called acuity and visibility hypotheses. The current epidemic of age-related macular degeneration has directed researchers to investigate the protective hypothesis of MP, while there has been a conspicuous lack of work designed to investigate the role of MP in visual performance. The aim of this review is to present and critically appraise the current literature germane to the contribution of MP, if any, to visual performance and experience.

  4. 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

  5. Stimulus edge effects in the measurement of macular pigment using heterochromatic flicker photometry.

    PubMed

    Smollon, William E; Wooten, Billy R; Hammond, Billy R

    2015-11-01

    Heterochromatic flicker photometry (HFP) is the most common technique of measuring macular pigment optical density (MPOD). Some data strongly suggest that HFP samples MPOD specifically at the edge of center-fixated circular stimuli. Other data have led to the conclusion that HFP samples over the entire area of the stimulus. To resolve this disparity, MPOD was measured using HFP and a series of solid discs of varying radii (0.25 to 2.0 deg) and with thin annuli corresponding to the edge of those discs. MPOD assessed with the two methods yielded excellent correspondence and linearity: Y=0.01+0.98X , r=0.96. A second set of experiments showed that if a disc stimulus is adjusted for no-flicker (the standard procedure) and simply reduced in size, no flicker is observed despite the higher level of MPOD in the smaller area. Taken together, these results confirm that MPOD is determined at the edge of the measuring stimulus when using stimulus sizes in the range that is in dispute (up to a radius of 0.75 deg). The basis for this edge effect can be explained by quantitative differences in the spatial-temporal properties of the visual field as a function of angular distance from the fixation point.

  6. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration.

    PubMed

    Ibrahim, Ahmed S; Mander, Suchreet; Hussein, Khaled A; Elsherbiny, Nehal M; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-02-23

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features.

  7. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

    PubMed Central

    Ibrahim, Ahmed S.; Mander, Suchreet; Hussein, Khaled A.; Elsherbiny, Nehal M.; Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-01-01

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE–photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features. PMID:26885895

  8. [Notalgia paresthetica, "posterior pigmented pruritic patch" and macular amyloidosis. Three stages of a disease].

    PubMed

    Cerroni, L; Kopera, D; Soyer, H P; Kerl, H

    1993-12-01

    We report on nine cases of notalgia paresthetica, a cutaneous condition that has rarely been described in the dermatological literature and is characterized by localized pruritus, burning and hyperesthesia and/or paresthesia on the back. Histological and immunohistochemical studies have not clarified the pathogenesis of this disease. Several factors might be involved in various cases, including increased cutaneous innervation and neuropathy. The so-called posterior pigmented pruritic patch and macular amyloidosis may be considered as progressive evolutional stages of notalgia paresthetica. PMID:8113041

  9. Progression of Idiopathic Eruptive Macular Pigmentation in a Girl from Childhood to Adolescence: Case Report and Literature Review.

    PubMed

    Tsai, Wen-Chien; Lan, Jui; Lee, Chih-Hung

    2016-09-01

    A 14-year-old girl developed brownish round macules and patches over the face, trunk, and proximal limbs with extensive progression since she was 7 years old. Electron microscopy examination revealed an increase in the number and maturity of melanosomes in basal and suprabasal keratinocytes, although the number of melanocytes was within the normal range. A diagnosis of idiopathic eruptive macular pigmentation was made. We describe the unusual disease progression of this case of idiopathic eruptive macular pigmentation, which was thought to be self-limited.

  10. Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes

    PubMed Central

    Sommerburg, O.; Keunen, J.; Bird, A.; van Kuijk, F. J G M

    1998-01-01

    BACKGROUND—It has been suggested that eating green leafy vegetables, which are rich in lutein and zeaxanthin, may decrease the risk for age related macular degeneration. The goal of this study was to analyse various fruits and vegetables to establish which ones contain lutein and/or zeaxanthin and can serve as possible dietary supplements for these carotenoids.
METHODS—Homogenates of 33 fruits and vegetables, two fruit juices, and egg yolk were used for extraction of the carotenoids with hexane. Measurement of the different carotenoids and their isomers was carried out by high performance liquid chromatography using a single column with an isocratic run, and a diode array detector.
RESULTS—Egg yolk and maize (corn) contained the highest mole percentage (% of total) of lutein and zeaxanthin (more than 85% of the total carotenoids). Maize was the vegetable with the highest quantity of lutein (60% of total) and orange pepper was the vegetable with the highest amount of zeaxanthin (37% of total). Substantial amounts of lutein and zeaxanthin (30-50%) were also present in kiwi fruit, grapes, spinach, orange juice, zucchini (or vegetable marrow), and different kinds of squash. The results show that there are fruits and vegetables of various colours with a relatively high content of lutein and zeaxanthin.
CONCLUSIONS—Most of the dark green leafy vegetables, previously recommended for a higher intake of lutein and zeaxanthin, have 15-47% of lutein, but a very low content (0-3%) of zeaxanthin. Our study shows that fruits and vegetables of various colours can be consumed to increase dietary intake of lutein and zeaxanthin.

 Keywords: age related macular degeneration; carotenoids; dietary intake; macular pigment PMID:9828775

  11. High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration

    PubMed Central

    Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung

    2016-01-01

    Purpose Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. Methods In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. Results The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Conclusions Increasing the dose of bevacizumab in refractory PED may be a possible treatment option. PMID:27478353

  12. Macular pigment density and distribution: comparison of fundus autofluorescence with minimum motion photometry.

    PubMed

    Robson, Anthony G; Moreland, Jack D; Pauleikhoff, Daniel; Morrissey, Tony; Holder, Graham E; Fitzke, Fred W; Bird, Alan C; van Kuijk, Frederik J G M

    2003-07-01

    Macular pigment (MP) distribution profiles were measured for 18 subjects using a Moreland anomaloscope modified for motion photometry. The total amount of MP within the central 7 degrees was estimated from the distribution profile by numerical integration. Fundus autofluorescence images were obtained for eight of these subjects using a scanning laser ophthalmoscope. Peak optical density of MP increased with the total amount present, but the correlation was weakened by inter-subject differences in MP distribution. The mean MP distribution derived from mean grey-scale profiles of fundus autofluorescence images correlated closely with that obtained psychophysically (r=0.96). Autofluorescence imaging provides a fast non-invasive method for assessing MP in vivo.

  13. Effect of Supplemental Lutein and Zeaxanthin on Serum, Macular Pigmentation, and Visual Performance in Patients with Early Age-Related Macular Degeneration

    PubMed Central

    Huang, Yang-Mu; Dou, Hong-Liang; Huang, Fei-Fei; Xu, Xian-Rong; Zou, Zhi-Yong

    2015-01-01

    Purpose. To compare the 2-year effect of multiple doses of lutein/zeaxanthin on serum, macular pigmentation, and visual performance on patients with early age-related macular degeneration (AMD). Methods. In this randomized, double-blinded, and placebo-controlled trial, 112 early AMD patients randomly received either 10 mg lutein, 20 mg lutein, a combination of lutein (10 mg) and zeaxanthin (10 mg), or placebo daily for 2 years. Serum concentration of lutein/zeaxanthin, macular pigment optical density (MPOD), visual functions including best-spectacle corrected visual acuity (BCVA), contrast sensitivity (CS), flash recovery time (FRT), and vision-related quality of life (VFQ25) was quantified. Results. Serum lutein concentration and MPOD significantly increased in all the active treatment groups. Supplementation with 20 mg lutein was the most effective in increasing MPOD and CS at 3 cycles/degree for the first 48 weeks. However, they both significantly increased to the same peak value following supplementation with either 10 mg or 20 mg lutein during the intervention. No statistical changes of BCVA or FRT were observed during the trial. Conclusions. Long-term lutein supplementation could increase serum lutein concentration, MPOD, and visual sensitivities of early AMD patients. 10 mg lutein daily might be an advisable long-term dosage for early AMD treatment. PMID:25815324

  14. Simple and objective method for routine detection of the macular pigment xanthophyll

    NASA Astrophysics Data System (ADS)

    Schweitzer, Dietrich; Jentsch, Susanne; Dawczynski, Jens; Hammer, Martin; Wolf-Schnurrbusch, Ute E. K.; Wolf, Sebastian

    2010-11-01

    A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R2 = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491+/-0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615+/-0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610+/-0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674+/-0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients.

  15. Caspase-14 expression impairs retinal pigment epithelium barrier function: potential role in diabetic macular edema.

    PubMed

    Beasley, Selina; El-Sherbiny, Mohamed; Megyerdi, Sylvia; El-Shafey, Sally; Choksi, Karishma; Kaddour-Djebbar, Ismail; Sheibani, Nader; Hsu, Stephen; Al-Shabrawey, Mohamed

    2014-01-01

    We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR). Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE) dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose) on caspase-14 expression in human RPE (ARPE-19) cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose). We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS) to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER). These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema. PMID:25121097

  16. Recovery of macular pigment spectrum in vivo using hyperspectral image analysis

    NASA Astrophysics Data System (ADS)

    Fawzi, Amani A.; Lee, Noah; Acton, Jennifer H.; Laine, Andrew F.; Smith, R. Theodore

    2011-10-01

    We investigated the feasibility of a novel method for hyperspectral mapping of macular pigment (MP) in vivo. Six healthy subjects were recruited for noninvasive imaging using a snapshot hyperspectral system. The three-dimensional full spatial-spectral data cube was analyzed using non-negative matrix factorization (NMF), wherein the data was decomposed to give spectral signatures and spatial distribution, in search for the MP absorbance spectrum. The NMF was initialized with the in vitro MP spectrum and rank 4 spectral signature decomposition was used to recover the MP spectrum and optical density in vivo. The recovered MP spectra showed two peaks in the blue spectrum, characteristic of MP, giving a detailed in vivo demonstration of these absorbance peaks. The peak MP optical densities ranged from 0.08 to 0.22 (mean 0.15+/-0.05) and became spatially negligible at diameters 1100 to 1760 μm (4 to 6 deg) in the normal subjects. This objective method was able to exploit prior knowledge (the in vitro MP spectrum) in order to extract an accurate in vivo spectral analysis and full MP spatial profile, while separating the MP spectra from other ocular absorbers. Snapshot hyperspectral imaging in combination with advanced mathematical analysis provides a simple cost-effective approach for MP mapping in vivo.

  17. The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration.

    PubMed

    Stringham, J M; Hammond, B R; Nolan, J M; Wooten, B R; Mammen, A; Smollon, W; Snodderly, D M

    2008-11-01

    The purpose of this study was to assess the utility and validity of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment optical density (MPOD) in patients with intermediate stages of age-related macular degeneration (AMD). The measurement procedure was optimized to accommodate individual differences in temporal vision related to age, disease, or other factors. The validity criteria were based on the similarity of the spectral absorption curves to ex vivo curves of lutein and zeaxanthin and the similarity of spatial density profiles to those measured in subjects without retinal disease. Macular pigment optical density (MPOD) spatial profiles were measured with an LED-based macular densitometer; spectral absorption curves were measured with a 3-channel Maxwellian view system including a monochromator. All patients were characterized via clinical exams and all but 2 subjects from whom data were obtained had masked grading of color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. Most of the patients were in AREDS category 2 (27%) or 3 (57%). Patients with visual acuity as poor as 20/80 were included, and could perform the task as long as they could see the stimulus. Eighty-one percent of the patients screened were able to perform the cHFP task, and data were obtained from 30 AMD patients. Spatial profiles of MPOD were measured in 19 subjects who could see the stimulus at all tested loci. These profiles were highly similar to those that have been measured with HFP in subjects without retinal disease. The average shape of the spectral absorption curves for the AMD subjects corresponded well to an ex vivo template. These data support both the utility and validity of the cHFP method for measuring MPOD in subjects with intermediate stages of AMD. The ability to measure the retinal response to nutritional intervention is of practical importance for monitoring patients being supplemented with lutein and

  18. Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements

    PubMed Central

    Okazaki, Shigetoshi; Gellermann, Werner; Bernstein, Paul S.

    2015-01-01

    Purpose To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. Methods Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. Results The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. “retinal responders”, who had an increase of both MPOD levels and serum lutein concentrations (n = 13), “retinal non-responders”, who had only increased serum concentrations and no change in MPOD levels (n = 20), and “retinal and serum non-responders”, who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in

  19. Research Resource: Nuclear Receptor Atlas of Human Retinal Pigment Epithelial Cells: Potential Relevance to Age-Related Macular Degeneration

    PubMed Central

    Dwyer, Mary A.; Kazmin, Dmitri; Hu, Peng; McDonnell, Donald P.

    2011-01-01

    Retinal pigment epithelial (RPE) cells play a vital role in retinal physiology by forming the outer blood–retina barrier and supporting photoreceptor function. Retinopathies including age-related macular degeneration (AMD) involve physiological and pathological changes in the epithelium, severely impairing the retina and effecting vision. Nuclear receptors (NRs), including peroxisome proliferator-activated receptor and liver X receptor, have been identified as key regulators of physiological pathways such as lipid metabolic dysregulation and inflammation, pathways that may also be involved in development of AMD. However, the expression levels of NRs in RPE cells have yet to be systematically surveyed. Furthermore, cell culture lines are widely used to study the biology of RPE cells, without knowledge of the differences or similarities in NR expression and activity between these in vitro models and in vivo RPE. Using quantitative real-time PCR, we assessed the expression patterns of all 48 members of the NR family plus aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator in human RPE cells. We profiled freshly isolated cells from donor eyes (in vivo), a spontaneously arising human cell line (in vitro), and primary cell culture lines (in vitro) to determine the extent to which NR expression in the cultured cell lines reflects that of in vivo. To evaluate the validity of using cell culture models for investigating NR receptor biology, we determined transcriptional activity and target gene expression of several moderately and highly expressed NRs in vitro. Finally, we identified a subset of NRs that may play an important role in pathobiology of AMD. PMID:21239617

  20. Spatial Mapping of Macular Pigment Optical Density and Its Relationship to Contrast Sensitivity and Glare Disability

    NASA Astrophysics Data System (ADS)

    Putnam, Christopher

    This dissertation explored the relationship of the macular pigment optical density (MPOD) spatial profile with measures of contrast sensitivity (CS), glare disability (GD), relative glare disability (RGD) and intraocular light scatter. A novel device capable of measuring MPOD across the central 160 of retina along 8 principle meridians using customized heterochromatic flicker photometry (cHFP) at eccentricities of 00, 20, 40, 60 and 80 was built. MPOD was calculated as both discrete and integrated values at all measured retinal loci. CS was measured using vertical grating stimuli of 3, 6 and 9 cycles per degree (cpd) also presented at 00, 20, 4 0, 60 and 80 eccentricity. GD was calculated as a difference in CS between glare and no glare conditions (CSNo Glare - CSGlare) using the same vertical grating stimuli presented at the same eccentricities. RGD [(CSNo Glare - CSGlare) / CSNo Glare] was calculated to isolate the glare attenuation effects of MPOD by controlling for CS variability among the subject sample. Intraocular scatter was assessed through a direct compensation method using a commercially available device. Statistical analyses of the discrete and integrated MPOD associations with CS, GD, RGD and intraocular scatter were evaluated. The cHFP identified reliable MPOD spatial distribution maps demonstrating a 1 st order exponential decay curve as a function of increasing eccentricity. Foveal MPOD revealed the highest correlation coefficients with RGD using 9cpd stimuli. These results are consistent with the glare attenuation effects of MP at higher spatial frequencies. Further support may be seen from the significant correlations found between corresponding parafoveal MPOD measures and both GD and RGD at 20 and 40 of eccentricity using 9cpd stimuli with greater MPOD being associated with less glare disability. All calculated measures of foveal MPOD shared similar significant correlation coefficients with both GD and RGD using 6cpd and 9cpd stimuli. Discrete

  1. Macular pigment optical density: repeatability, intereye correlation, and effect of ocular dominance

    PubMed Central

    Davey, Pinakin Gunvant; Alvarez, Silverio D; Lee, Jessica Y

    2016-01-01

    Purpose To evaluate short-term repeatability, intereye correlation, and effect of ocular dominance on macular pigment optical density (MPOD) measurements obtained using the QuantifEye Heterochromatic Flicker Photometer. Patients and methods A total of 72 study participants were enrolled in this prospective, cross-sectional study. Participants underwent a comprehensive ocular evaluation, including visual acuity, evaluation of ocular dominance, slit lamp examination, intraocular pressure measurement, and optic nerve head and macula analysis using optical coherence tomography and fundus photography. All study participants after initial training underwent MPOD measurement twice in both eyes in a randomized sequence. The repeatability was tested using Altman and Bland plots for first measurements with the second measurements for right eye and left eye and additionally by grouping eyes as a function of ocular dominance. The Pearson correlation coefficient was performed to assess the intereye correlation of MPOD values. Results The mean age of study participants was 35.5 years (range 22–68 years). The mean MPOD measurements for OD (right eye) and OS (left eye) were 0.47 and 0.48, respectively, which followed a normal distribution (Shapiro–Wilk test, P=0.6 and 0.2). The 95% limits of agreement of Altman and Bland plots for the first and second measurements were −0.12 to +0.11 and −0.13 to +0.12 for OD and OS, respectively. The correlation coefficient of mean MPOD measurements of OD and OS was r statistic =0.94 (Pearson correlation coefficient P<0.0001; r2 0.89). The 95% limits of agreement of Altman and Bland plots when evaluated by laterality of eye or by ocular dominance were narrow, with limits of agreement ranging from −0.13 to +0.12. Conclusion The MPOD measurements obtained using the QuantifEye show good short-term repeatability. There is excellent intereye correlation, indicating that the MPOD values of one eye data can predict the fellow eye value with 89

  2. Macular pigment optical density: repeatability, intereye correlation, and effect of ocular dominance

    PubMed Central

    Davey, Pinakin Gunvant; Alvarez, Silverio D; Lee, Jessica Y

    2016-01-01

    Purpose To evaluate short-term repeatability, intereye correlation, and effect of ocular dominance on macular pigment optical density (MPOD) measurements obtained using the QuantifEye Heterochromatic Flicker Photometer. Patients and methods A total of 72 study participants were enrolled in this prospective, cross-sectional study. Participants underwent a comprehensive ocular evaluation, including visual acuity, evaluation of ocular dominance, slit lamp examination, intraocular pressure measurement, and optic nerve head and macula analysis using optical coherence tomography and fundus photography. All study participants after initial training underwent MPOD measurement twice in both eyes in a randomized sequence. The repeatability was tested using Altman and Bland plots for first measurements with the second measurements for right eye and left eye and additionally by grouping eyes as a function of ocular dominance. The Pearson correlation coefficient was performed to assess the intereye correlation of MPOD values. Results The mean age of study participants was 35.5 years (range 22–68 years). The mean MPOD measurements for OD (right eye) and OS (left eye) were 0.47 and 0.48, respectively, which followed a normal distribution (Shapiro–Wilk test, P=0.6 and 0.2). The 95% limits of agreement of Altman and Bland plots for the first and second measurements were −0.12 to +0.11 and −0.13 to +0.12 for OD and OS, respectively. The correlation coefficient of mean MPOD measurements of OD and OS was r statistic =0.94 (Pearson correlation coefficient P<0.0001; r2 0.89). The 95% limits of agreement of Altman and Bland plots when evaluated by laterality of eye or by ocular dominance were narrow, with limits of agreement ranging from −0.13 to +0.12. Conclusion The MPOD measurements obtained using the QuantifEye show good short-term repeatability. There is excellent intereye correlation, indicating that the MPOD values of one eye data can predict the fellow eye value with 89

  3. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients.

    PubMed

    Song, Won Kyung; Park, Kyung-Mi; Kim, Hyun-Ju; Lee, Jae Ho; Choi, Jinjung; Chong, So Young; Shim, Sung Han; Del Priore, Lucian V; Lanza, Robert

    2015-05-12

    Embryonic stem cells hold great promise for various diseases because of their unlimited capacity for self-renewal and ability to differentiate into any cell type in the body. However, despite over 3 decades of research, there have been no reports on the safety and potential efficacy of pluripotent stem cell progeny in Asian patients with any disease. Here, we report the safety and tolerability of subretinal transplantation of human embryonic-stem-cell (hESC)-derived retinal pigment epithelium in four Asian patients: two with dry age-related macular degeneration and two with Stargardt macular dystrophy. They were followed for 1 year. There was no evidence of adverse proliferation, tumorigenicity, ectopic tissue formation, or other serious safety issues related to the transplanted cells. Visual acuity improved 9-19 letters in three patients and remained stable (+1 letter) in one patient. The results confirmed that hESC-derived cells could serve as a potentially safe new source for regenerative medicine.

  4. Macular Pigment Optical Density in Chinese Primary Open Angle Glaucoma Using the One-Wavelength Reflectometry Method

    PubMed Central

    Ji, Yuying; Zuo, Chengguo; Lin, Mingkai; Zhang, Xiongze; Li, Miaoling; Mi, Lan; Liu, Bing; Wen, Feng

    2016-01-01

    Purpose. To investigate macular pigment optical density (MPOD) and its relationship with retinal thickness in primary open angle glaucoma (POAG) patients using the one-wavelength reflectometry method. Methods. A total of 30 eyes from 30 POAG patients (18 males and 12 females, mean age 47.27 ± 16.93) and 52 eyes from 52 controls (27 males and 25 females, mean age 49.54 ± 19.15) were included in this prospective, observational, case-control study. MPOD was measured in a 7-degree area using one-wavelength reflectometry method. Two parameters, max and mean optical density (OD), were used for analyses. Spectral-domain-optical coherence tomography was used to measure retinal thickness, including central retinal thickness (CRT), the macular ganglion cell complex (GCC), and the circumpapillary retinal nerve fiber layer (RNFL). Results. Both maxOD and meanOD were significantly reduced in POAG patients compared with normal subjects (P < 0.001). GCC, CRT, and RNFL thicknesses were also significantly reduced in POAG patients (P < 0.001). GCC thickness had a positive relationship with MPOD. Conclusions. MPOD within the 7-degree area was significantly lower in Chinese POAG patients than in control subjects, and GCC thickness was significantly and positively associated with MPOD. Whether the observed lower MPOD in POAG contributes to the disease process or is secondary to pathological changes caused by the disease (such as loss of ganglion cells) warrants further and longitudinal study. PMID:27144013

  5. Macular Pigment Optical Density in Chinese Primary Open Angle Glaucoma Using the One-Wavelength Reflectometry Method.

    PubMed

    Ji, Yuying; Zuo, Chengguo; Lin, Mingkai; Zhang, Xiongze; Li, Miaoling; Mi, Lan; Liu, Bing; Wen, Feng

    2016-01-01

    Purpose. To investigate macular pigment optical density (MPOD) and its relationship with retinal thickness in primary open angle glaucoma (POAG) patients using the one-wavelength reflectometry method. Methods. A total of 30 eyes from 30 POAG patients (18 males and 12 females, mean age 47.27 ± 16.93) and 52 eyes from 52 controls (27 males and 25 females, mean age 49.54 ± 19.15) were included in this prospective, observational, case-control study. MPOD was measured in a 7-degree area using one-wavelength reflectometry method. Two parameters, max and mean optical density (OD), were used for analyses. Spectral-domain-optical coherence tomography was used to measure retinal thickness, including central retinal thickness (CRT), the macular ganglion cell complex (GCC), and the circumpapillary retinal nerve fiber layer (RNFL). Results. Both maxOD and meanOD were significantly reduced in POAG patients compared with normal subjects (P < 0.001). GCC, CRT, and RNFL thicknesses were also significantly reduced in POAG patients (P < 0.001). GCC thickness had a positive relationship with MPOD. Conclusions. MPOD within the 7-degree area was significantly lower in Chinese POAG patients than in control subjects, and GCC thickness was significantly and positively associated with MPOD. Whether the observed lower MPOD in POAG contributes to the disease process or is secondary to pathological changes caused by the disease (such as loss of ganglion cells) warrants further and longitudinal study. PMID:27144013

  6. Genetic Determinants of Macular Pigments in Women of the Carotenoids in Age-Related Eye Disease Study

    PubMed Central

    Meyers, Kristin J.; Johnson, Elizabeth J.; Bernstein, Paul S.; Iyengar, Sudha K.; Engelman, Corinne D.; Karki, Chitra K.; Liu, Zhe; Igo, Robert P.; Truitt, Barbara; Klein, Michael L.; Snodderly, D. Max; Blodi, Barbara A.; Gehrs, Karen M.; Sarto, Gloria E.; Wallace, Robert B.; Robinson, Jennifer; LeBlanc, Erin S.; Hageman, Gregory; Tinker, Lesley; Mares, Julie A.

    2013-01-01

    Purpose. To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study. Methods. 1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression. Results. Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA = 0.029, P = 2.2 × 10−4). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10−11). Conclusions. Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD. PMID:23404124

  7. The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration

    PubMed Central

    Zanzottera, Emma C.; Messinger, Jeffrey D.; Ach, Thomas; Smith, R. Theodore; Freund, K. Bailey; Curcio, Christine A.

    2015-01-01

    Purpose. To seek pathways of retinal pigment epithelium (RPE) fate in age-related macular degeneration via a morphology grading system; provide nomenclature, visualization targets, and metrics for clinical imaging and model systems. Methods. Donor eyes with geographic atrophy (GA) or choroidal neovascularization (CNV) and one GA eye with previous clinical spectral-domain optical coherence tomography (SDOCT) imaging were processed for histology, photodocumented, and annotated at predefined locations. Retinal pigment epithelial cells contained spindle-shaped melanosomes, apposed a basal lamina or basal laminar deposit (BLamD), and exhibited recognizable morphologies. Thicknesses and unbiased estimates of frequencies were obtained. Results. In 13 GA eyes (449 locations), ‘Shedding,’ ‘Sloughed,’ and ‘Dissociated’ morphologies were abundant; 22.2% of atrophic locations had ‘Dissociated’ RPE. In 39 CNV eyes (1363 locations), 37.3% of locations with fibrovascular/fibrocellular scar had ‘Entombed’ RPE; ‘Sloughed,’ ‘Dissociated,’ and ‘Bilaminar’ morphologies were abundant. Of abnormal RPE, CNV and GA both had ∼35% ‘Sloughed’/‘Intraretinal,’ with more Intraretinal in CNV (9.5% vs. 1.8%). ‘Shedding’ cells associated with granule aggregations in BLamD. The RPE layer did not thin, and BLamD remained thick, with progression. Granule-containing material consistent with three morphologies correlated to SDOCT hyperreflective foci in the previously examined GA patient. Conclusions. Retinal pigment epithelium morphology indicates multiple pathways in GA and CNV. Atrophic/scarred areas have numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates, possibly apoptotic, are visible in SDOCT, as are ‘Dissociated’ and ‘Sloughed’ cells. The significance of RPE phenotypes is addressable in longitudinal, high-resolution imaging in clinic populations. Data can motivate future molecular phenotyping

  8. Lutein and zeaxanthin: Role as macular pigment and factors that control bioavailability from egg yolks and nanoemulsions

    NASA Astrophysics Data System (ADS)

    Vishwanathan, Rohini

    Lutein and zeaxanthin, two oxygenated carotenoids, exclusively accumulate in the macula, protecting the underlying photoreceptors and retinal pigment epithelial cells from damaging blue radiation of sunlight. As macular pigment, lutein and zeaxanthin are also potent antioxidants protecting the vulnerable regions of retina from free radical injury. Oxidative stress and cumulative light damage play an important role in pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly population. Antioxidant and lutein supplementation has been shown to decrease the risk and prevent the progression of AMD. The egg yolk is a highly bioavailable source of lutein and zeaxanthin and thus a possible contender for AMD prevention and treatment. Consumption of 2 egg yolks/d for 5 weeks was shown herein to significantly increase serum lutein and zeaxanthin concentration and clinically improve macular pigment concentrations at 0.5° retinal eccentricity in an older adult population taking cholesterol-lowering statins. Four egg yolks/d not only raised serum lutein and zeaxanthin significantly but also macular pigment densities at 0.25°, 0.5° and 1° retinal eccentricity. A positive outcome of the 2 egg yolk consumption was the significant increase in serum HDL-C with a tendency of serum LDL-C to decrease, although not significantly. Four egg yolks/d seemed to cross the threshold for dietary cholesterol tolerance as serum LDL-C tended to increase, although not significantly, despite the significant increase in serum HDL-C. There is a strong possibility that greater build up of lutein and zeaxanthin in the macula may have been observed with 2 egg yolks/d if the intervention period was longer than 5 weeks. Addition of up to 2 eggs a day to the diet is suggested to benefit an older adult population, especially those who are already taking cholesterol-lowering statins by (a) building their macular pigment and possibly protect against AMD and (b

  9. Lutein and zeaxanthin: Role as macular pigment and factors that control bioavailability from egg yolks and nanoemulsions

    NASA Astrophysics Data System (ADS)

    Vishwanathan, Rohini

    Lutein and zeaxanthin, two oxygenated carotenoids, exclusively accumulate in the macula, protecting the underlying photoreceptors and retinal pigment epithelial cells from damaging blue radiation of sunlight. As macular pigment, lutein and zeaxanthin are also potent antioxidants protecting the vulnerable regions of retina from free radical injury. Oxidative stress and cumulative light damage play an important role in pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly population. Antioxidant and lutein supplementation has been shown to decrease the risk and prevent the progression of AMD. The egg yolk is a highly bioavailable source of lutein and zeaxanthin and thus a possible contender for AMD prevention and treatment. Consumption of 2 egg yolks/d for 5 weeks was shown herein to significantly increase serum lutein and zeaxanthin concentration and clinically improve macular pigment concentrations at 0.5° retinal eccentricity in an older adult population taking cholesterol-lowering statins. Four egg yolks/d not only raised serum lutein and zeaxanthin significantly but also macular pigment densities at 0.25°, 0.5° and 1° retinal eccentricity. A positive outcome of the 2 egg yolk consumption was the significant increase in serum HDL-C with a tendency of serum LDL-C to decrease, although not significantly. Four egg yolks/d seemed to cross the threshold for dietary cholesterol tolerance as serum LDL-C tended to increase, although not significantly, despite the significant increase in serum HDL-C. There is a strong possibility that greater build up of lutein and zeaxanthin in the macula may have been observed with 2 egg yolks/d if the intervention period was longer than 5 weeks. Addition of up to 2 eggs a day to the diet is suggested to benefit an older adult population, especially those who are already taking cholesterol-lowering statins by (a) building their macular pigment and possibly protect against AMD and (b

  10. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    PubMed Central

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new therapeutics. This requires further in-depth knowledge of the similarities and differences between mouse and human RPE. Methods We performed a microarray study to identify and functionally annotate RPE specific gene expression in mouse and human RPE. We used a meticulous method to determine C57BL/6J mouse RPE signature genes, correcting for possible RNA contamination from its adjacent layers: the choroid and the photoreceptors. We compared the signature genes, gene expression profiles and functional annotations of the mouse and human RPE. Results We defined sets of mouse (64), human (171) and mouse–human interspecies (22) RPE signature genes. Not unexpectedly, our gene expression analysis and comparative functional annotation suggested that, in general, the mouse and human RPE are very similar. For example, we found similarities for general features, like “organ development” and “disorders related to neurological tissue”. However, detailed analysis of the molecular pathways and networks associated with RPE functions, suggested also multiple species-specific differences, some of which may be relevant for the development of AMD. For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE. Furthermore, functions assigned to mouse and human RPE expression profiles indicate (patho-) biological differences related to AMD, such as oxidative stress, Bruch’s membrane, immune-regulation and outer blood retina barrier. Conclusion These differences may be important for the development of new therapeutic strategies and translational studies in age-related macular

  11. Concordance of macular pigment measurements obtained using customized heterochromatic flicker photometry, dual-wavelength autofluorescence, and single-wavelength reflectance.

    PubMed

    Dennison, Jessica L; Stack, Jim; Beatty, Stephen; Nolan, John M

    2013-11-01

    This study compares in vivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer(™)), dual-wavelength fundus autofluorescence (Heidelberg Spectralis(®) HRA + OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam(®) 200). MP was measured in one eye of 62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis. Agreement between the Densitometer and Spectralis was investigated at various eccentricities using a variety of quantitative and graphical methods, including: Pearson correlation coefficient to measure degree of scatter (precision), accuracy coefficient, concordance correlation coefficient (ccc), paired t-test, scatter and Bland-Altman plots. The relationship between max MP from the Visucam and central MP from the Spectralis and Densitometer was investigated using regression methods. Agreement was strong between the Densitometer and Spectralis at all central eccentricities (e.g. at 0.25° eccentricity: accuracy = 0.97, precision = 0.90, ccc = 0.87). Regression analysis showed a very weak relationship between the Visucam and Densitometer (e.g. Visucam max on Densitometer central MP: R(2) = 0.008, p = 0.843). Regression analysis also demonstrated a weak relationship between MP measured by the Spectralis and Visucam (e.g. Visucam max on Spectralis central MP: R(2) = 0.047, p = 0.348). MP values obtained using the Heidelberg Spectralis are comparable to MP values obtained using the Densitometer. In contrast, MP values obtained using the Zeiss Visucam are not comparable with either the Densitometer or the Spectralis MP measuring devices. Taking cHFP as the current standard to which other MP measuring devices should be compared, the Spectralis is suitable for use in a clinical and research setting, whereas the Visucam is not.

  12. [Macular serpiginous choroiditis complicated by macular hole].

    PubMed

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    Macular serpiginouschoroiditis is a rare variant of serpiginous choroiditis characterized by a severe recurrent inflammation of both central choroid and retinal pigment epithelium. Visual prognosis is severe due to subsequent distruction of retinal structures. Permanent central visual loss is the consequence of retinal pigment epithelium hyper or hypoplasia and/or subretinal neovascularization leading to fibrous scarring. This article reports the unusual case of rapid development of a macular hole soon after the onset of characteristic clinical features. Despite anti-inflammatory treatment and successful macular hole surgery the visual function remained significantly impaired by secondary central retinal pigment epithelium changes.

  13. Resonant imaging of carotenoid pigments in the human retina

    NASA Astrophysics Data System (ADS)

    Gellermann, Werner; Emakov, Igor V.; McClane, Robert W.

    2002-06-01

    We have generated high spatial resolution images showing the distribution of carotenoid macular pigments in the human retina using Raman spectroscopy. A low level of macular pigments is associated with an increased risk of developing age-related macular degeneration, a leading cause of irreversible blindness. Using excised human eyecups and resonant excitation of the pigment molecules with narrow bandwidth blue light from a mercury arc lamp, we record Raman images originating from the carbon-carbon double bond stretch vibrations of lutein and zeaxanthin, the carotenoids comprising human macular pigments. Our Raman images reveal significant differences among subjects, both in regard to absolute levels as well as spatial distribution within the macula. Since the light levels used to obtain these images are well below established safety limits, this technique holds promise for developing a rapid screening diagnostic in large populations at risk for vision loss from age-related macular degeneration.

  14. N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration.

    PubMed

    Voloboueva, Ludmila A; Killilea, David W; Atamna, Hani; Ames, Bruce N

    2007-12-01

    Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in the elderly in developed countries. AMD patients have elevated levels of iron within the retinal pigment epithelia (RPE), which may lead to oxidative damage to mitochondria, disruption of retinal metabolism, and vision impairment or loss. As a possible model for iron-induced AMD, we investigated the effects of excess iron in cultured human fetal RPE cells on oxidant levels and mitochondrial cytochrome c oxidase (complex IV) function and tested for protection by N-tert-butyl hydroxylamine (NtBHA), a known mitochondrial antioxidant. RPE exposure to ferric ammonium citrate resulted in a time- and dose-dependent increase in intracellular iron, which increased oxidant production and decreased glutathione (GSH) levels and mitochondrial complex IV activity. NtBHA addition to iron-overloaded RPE cells led to a reduction of intracellular iron content, oxidative stress, and partial restoration of complex IV activity and GSH content. NtBHA might be useful in AMD due to its potential to reduce oxidative stress, mitochondrial damage, and age-related iron accumulation, which may damage normal RPE function and lead to loss of vision.

  15. Correspondence between retinal reflectometry and a flicker-based technique in the measurement of macular pigment spatial profiles

    NASA Astrophysics Data System (ADS)

    van der Veen, Rob L. P.; Berendschot, Tos T. J. M.; Makridaki, Maria; Hendrikse, Fred; Carden, David; Murray, Ian J.

    2009-11-01

    A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We found a strong correlation between the two techniques. However, the absolute estimates obtained by fundus reflectometry data were higher than by HFP. These differences could partly be explained by the fact that at 8 deg eccentricity the MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for eccentricities of <1 deg, we had to assume that subjects set flicker thresholds at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are very similar for both techniques if, on average, 0.05 DU is added to the HFP data at all eccentricities. An additional correction factor, dependent on the steepness of the MPOD spatial distribution, is required for 0 deg.

  16. Non-responsiveness to intravitreal aflibercept treatment in neovascular age-related macular degeneration: implications of serous pigment epithelial detachment

    PubMed Central

    Nagai, Norihiro; Suzuki, Misa; Uchida, Atsuro; Kurihara, Toshihide; Kamoshita, Mamoru; Minami, Sakiko; Shinoda, Hajime; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    The prognosis of neovascular age-related macular degeneration (AMD) has been improved by anti-vascular endothelial growth factor treatments, including intravitreal aflibercept (IVA) treatment. However, many patients remain incurable. In this study, we retrospectively evaluated non-responsiveness to IVA monotherapy at 12 months in 133 eyes of 133 AMD patients. Sixty-two patients were initially treatment-naive, and 71 had received other treatments before IVA (the treatment-switched group). Mean best-corrected visual acuity (BCVA) was improved in the treatment-naive group but not in the treatment-switched group, although mean central retinal thickness (CRT) decreased in both groups. The respective percentages of non-responders as determined by worsened BCVA in the treatment-naive and treatment-switched groups were 8.1% and 15.5%, and via fundus findings, they were 12.9% and 8.5%. Multivariate analyses adjusted for age, gender, CRT, and greatest linear dimension showed that serous pigment epithelial detachment (PED) at baseline was associated with non-responsiveness in both groups as determined by BCVA and by fundus findings, and fibrovascular PED measurements indicated no response as determined by fundus findings in the treatment-switched group. The results reported herein may assist the formulation of appropriate treatment protocols for AMD patients. PMID:27403807

  17. Innovative Troxler-free measurement of macular pigment and lens density with correction of the former for the aging lens.

    PubMed

    Bone, Richard A; Mukherjee, Anirbaan

    2013-10-01

    Simplified measurement of macular pigment optical density (MPOD) is important because of the ocular health benefits that are attributed to these retinal carotenoids. Here, we describe a novel instrument designed for this purpose, based on heterochromatic flicker photometry (HFP), which removes a number of difficulties that subjects often experience with traditional HFP. The instrument generates 1.5- and 15-deg diameter, centrally viewed stimuli that alternate between blue and green colors generated by light emitting diodes (LED). The 15 deg stimulus replaces the small, eccentrically viewed stimulus used in traditional HFP. Subjects adjust the blue LED intensity until flicker is eliminated in the case of the 1.5 deg stimulus and eliminated around the periphery in the case of the 15 deg stimulus. A microprocessor computes the subject's MPOD, in addition to the lens OD, and uses the latter to correct the MPOD. Good repeatability was confirmed through test-retest measurements on 52 subjects. The overwhelming majority of them stated that they found the test easy. The importance of the lens correction on MPOD measurements was confirmed in a simulation study. The study showed that, without the correction, MPOD would show an apparent age-related decline in a population for whom there was no real age dependence.

  18. Characterization of the Role of β-Carotene 9,10-Dioxygenase in Macular Pigment Metabolism*

    PubMed Central

    Babino, Darwin; Palczewski, Grzegorz; Widjaja-Adhi, M. Airanthi K.; Kiser, Philip D.; Golczak, Marcin; von Lintig, Johannes

    2015-01-01

    A family of enzymes collectively referred to as carotenoid cleavage oxygenases is responsible for oxidative conversion of carotenoids into apocarotenoids, including retinoids (vitamin A and its derivatives). A member of this family, the β-carotene 9,10-dioxygenase (BCO2), converts xanthophylls to rosafluene and ionones. Animals deficient in BCO2 highlight the critical role of the enzyme in carotenoid clearance as accumulation of these compounds occur in tissues. Inactivation of the enzyme by a four-amino acid-long insertion has recently been proposed to underlie xanthophyll concentration in the macula of the primate retina. Here, we focused on comparing the properties of primate and murine BCO2s. We demonstrate that the enzymes display a conserved structural fold and subcellular localization. Low temperature expression and detergent choice significantly affected binding and turnover rates of the recombinant enzymes with various xanthophyll substrates, including the unique macula pigment meso-zeaxanthin. Mice with genetically disrupted carotenoid cleavage oxygenases displayed adipose tissue rather than eye-specific accumulation of supplemented carotenoids. Studies in a human hepatic cell line revealed that BCO2 is expressed as an oxidative stress-induced gene. Our studies provide evidence that the enzymatic function of BCO2 is conserved in primates and link regulation of BCO2 gene expression with oxidative stress that can be caused by excessive carotenoid supplementation. PMID:26307071

  19. Association of macular pigment optical density with early stage of non-proliferative diabetic retinopathy in Chinese patients with type 2 diabetes mellitus

    PubMed Central

    She, Chong-Yang; Gu, Hong; Xu, Jun; Yang, Xiu-Fen; Ren, Xue-Tao; Liu, Ning-Pu

    2016-01-01

    AIM To detect the association between macular pigment optical density (MPOD), which reflects the antioxidant ability of retina, and diabetic retinopathy (DR) and to investigate the correlated factors of MPOD. METHODS Totally 435 subjects of urban Chinese were recruited to the study and divided into 3 groups: non-diabetes mellitus controls (NDM), diabetic patients without retinopathy (DWR), and patients with early stage of non-proliferative diabetic retinopathy (DR). Demographic and lifestyle characteristics were ascertained by questionnaire. A food-frequency questionnaire, general physical and ophthalmic examinations were completed for all participants. MPOD was measured by heterochromatic flicker photometry. Foveal thickness was measured by optical coherence tomography. The difference of MPOD among 3 groups was analyzed by analysis of covariance. The correlation analyses of MPOD with the candidate influence factors were assessed using the generalized estimating equations (GEE) model. RESULTS Of the 435 participants, 34 could not perform the MPOD measurements. Final analysis included 401 subjects, including 48 were in DR group, 134 in DWR group, and 219 in NDM group. MPOD was not significantly different among DR (0.49±0.21), DWR (0.45±0.21), and NDM (0.49±0.17) groups (P=0.24) after adjustment for fasting plasma glycemia, central foveal thickness, green vegetables, Chinese wolfberry, carotene and vitamin E. For all the 401 participants included, MPOD was positively associated with central foveal thickness (E=0.0007, P=0.001), Chinese wolfberry (E=0.0345, P=0.01), and green vegetables (E=0.0596, P<0.001) intake. CONCLUSION The data suggest that MPOD level is not statistically significantly influenced by the onset of diabetes or early stage of DR in the studied population. MPOD level is positively associated with thicker central foveal thickness and higher intake of foods containing carotenoids. PMID:27803860

  20. Autologous transplantation of genetically modified iris pigment epithelial cells: A promising concept for the treatment of age-related macular degeneration and other disorders of the eye

    NASA Astrophysics Data System (ADS)

    Semkova, Irina; Kreppel, Florian; Welsandt, Gerhard; Luther, Thomas; Kozlowski, Jolanta; Janicki, Hanna; Kochanek, Stefan; Schraermeyer, Ulrich

    2002-10-01

    Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.

  1. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration.

    PubMed

    Zhang, J; Bai, Y; Huang, L; Qi, Y; Zhang, Q; Li, S; Wu, Y; Li, X

    2015-11-12

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial (RPE) cells is a crucial causative factor responsible for the onset and progression of AMD. A2E, a major component of toxic lipofuscin implicated in AMD, is deposited in RPE cells with age. However, the mechanism whereby A2E may contribute to the pathogenesis of AMD remains unclear. We demonstrated that A2E was a danger signal of RPE cells, which induced autophagy and decreased cell viability in a concentration- and time-dependent manner. Within 15 min after the treatment of RPE with 25 μM A2E, the induction of autophagosome was detected by transmission electron microscopy. After continuous incubating RPE cells with A2E, intense punctate staining of LC3 and increased expression of LC3-II and Beclin-1 were identified. Meanwhile, the levels of intercellular adhesion molecule (ICAM), interleukin (IL)1β, IL2, IL-6, IL-8, IL-17A, IL-22, macrophage cationic peptide (MCP)-1, stromal cell-derived factor (SDF)-1, and vascular endothelial growth factor A (VEGFA) were elevated. The autophagic inhibitor 3-methyladenine (3-MA) and activator rapamycin were also used to verify the effect of autophagy on RPE cells against A2E. Our results revealed that 3-MA decreased the autophagosomes and LC3 puncta induced by A2E, increased inflammation-associated protein expression including ICAM, IL1β, IL2, IL-6, IL-8, IL-17A, IL-22, and SDF-1, and upregulated VEGFA expression. Whereas rapamycin augmented the A2E-mediated autophagy, attenuated protein expression of inflammation-associated and angiogenic factors, and blocked the Akt/mTOR pathway. Taken together, A2E induces autophagy in RPE cells at the early stage of incubation, and this autophagic response can be inhibited by 3-MA or augmented by rapamycin via the mTOR pathway. The enhancement of autophagy has a protective role in RPE cells against the adverse effects of A2E by reducing the

  2. A novel fluorescence-based assay for measuring A2E removal from human retinal pigment epithelial cells to screen for age-related macular degeneration inhibitors.

    PubMed

    Jin, Hong Lan; Lee, Sung-Chan; Kwon, Yong Sam; Choung, Se-Young; Jeong, Kwang Won

    2016-01-01

    Age-related macular degeneration (AMD) is a common retinal disease that leads to irreversible central vision loss in the elderly population. Recent studies have identified many factors related to the development of dry AMD, such as aging, cigarette smoking, genetic predispositions, and oxidative stress, eventually inducing the accumulation of lipofuscin, which is one of the most critical risk factors. One of the major lipofuscins in retinal pigment epithelial (RPE) cells is N-retinylidene-N-retinylethanolamine (also known as A2E), a pyridinium bis-retinoid. Currently there is a lack of effective therapy to prevent or restore vision loss caused by dry AMD. Recent studies have shown that 430 nm blue light induces the oxidation of A2E and the activation of caspase-3 to subsequently cause the death of RPE cells, suggesting that removal of A2E from retinal pigment cells might be critical for preventing AMD. Here, we developed a fluorescence-labeled A2E analog (A2E-BDP) that functions similar to A2E in RPE cells, but is more sensitive to detection than A2E. A2E-BDP-based tracing of intracellular A2E will be helpful, not only for studying the accumulation and removal of A2E in human RPE cells but also for identifying possible inhibitors of AMD. PMID:26604166

  3. Genetics Home Reference: vitelliform macular dystrophy

    MedlinePlus

    ... faces. Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the ... structures in these cells that contain light-sensing pigments. It is unclear why PRPH2 mutations affect only ...

  4. Clearance of autophagy-associated dying retinal pigment epithelial cells – a possible source for inflammation in age-related macular degeneration

    PubMed Central

    Szatmári-Tóth, M; Kristóf, E; Veréb, Z; Akhtar, S; Facskó, A; Fésüs, L; Kauppinen, A; Kaarniranta, K; Petrovski, G

    2016-01-01

    Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis. PMID:27607582

  5. High-speed two-photon excited autofluorescence imaging of ex vivo human retinal pigment epithelial cells toward age-related macular degeneration diagnostic.

    PubMed

    La Schiazza, Olivier; Bille, Josef F

    2008-01-01

    Age-related macular degeneration (AMD) is among the major concerns in ophthalmology, as it is the primary cause for irreversible blindness in developed countries. Nevertheless, there is poor understanding of the origins and mechanisms that trigger this important ocular disease. In common clinical pratice, AMD is monitored by autofluorescence imaging of the retinal pigment epithelial (RPE) cells through a confocal scanning laser ophthalmoscope. The RPE cells derive their dominant autofluorescence from the lipofuscin granules that accumulate in the cytoplasm with increasing age and disease. We explored a different approach to retinal RPE imaging using two-photon excited autofluorescence, offering intrinsic three-dimensional resolution, larger sensing depth and reduced photodamage compared to single-photon excited fluorescence ophthalmoscopy. A two-photon microscope, based on the architecture of a conventional scanning laser ophthalmoscope (HRT, Heidelberg Engineering, Germany), was designed for autofluorescence imaging on retina samples from postmortem human-donor eyes. We were able to visualize at video-rate speed single RPE lipofuscin granules, demonstrating the potential to develop this method toward clinical practice for patients with RPE-related retinal disease like AMD.

  6. Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration.

    PubMed

    Szatmári-Tóth, M; Kristóf, E; Veréb, Z; Akhtar, S; Facskó, A; Fésüs, L; Kauppinen, A; Kaarniranta, K; Petrovski, G

    2016-01-01

    Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis. PMID:27607582

  7. Change of retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in exudative age-related macular degeneration

    PubMed Central

    Kim, Moosang; Kim, Eung Suk; Seo, Kyung Hoon; Yu, Seung-Young; Kwak, Hyung-Woo

    2016-01-01

    Purpose: The study aimed to investigate the quantitative changes of retinal pigment epithelial (RPE) atrophy during a 24-month follow-up period of anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (AMD). Materials and Methods: This is a retrospective study. Sixty-five eyes of 62 consecutive patients with naïve exudative AMD who had received treatment with anti-VEGF therapy and followed for more 24 months were enrolled. All patients received three initial monthly injections of anti-VEGF (ranibizumab or bevacizumab), followed by pro re nata or treat-and-extend protocol. Color fundus image, optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy. Multiple regression analysis was performed to investigate the predictive factors found during univariate analysis to identify an association with increased RPE atrophic areas. Results: The mean number of anti-VEGF treatments was 9.18. RPE atrophic area was 1.293 ± 1.298 mm2 at baseline and enlarged to 2.394 ± 1.940 mm2 after 24 months, which differed significantly (P = 0.001). Multiple regression analysis revealed that larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF treatments were associated with increased RPE atrophic areas. Conclusions: RPE atrophy progresses in eyes with exudative AMD during anti-VEGF treatment. Larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF injections were associated with an increased risk of progression of RPE atrophy the following treatment. These findings may be useful to clinicians using intravitreal anti-VEGF for the treatment of exudative AMD, both for selecting an appropriate treatment plan and for predicting the progression of RPE atrophy. PMID:27488150

  8. Macular degeneration

    MedlinePlus

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  9. Retinal pigment epithelial cell proliferation

    PubMed Central

    Temple, Sally

    2015-01-01

    The human retinal pigment epithelium forms early in development and subsequently remains dormant, undergoing minimal proliferation throughout normal life. Retinal pigment epithelium proliferation, however, can be activated in disease states or by removing retinal pigment epithelial cells into culture. We review the conditions that control retinal pigment epithelial proliferation in culture, in animal models and in human disease and interpret retinal pigment epithelium proliferation in context of the recently discovered retinal pigment epithelium stem cell that is responsible for most in vitro retinal pigment epithelial proliferation. Retinal pigment epithelial proliferation-mediated wound repair that occurs in selected macular diseases is contrasted with retinal pigment epithelial proliferation-mediated fibroblastic scar formation that underlies proliferative vitreoretinopathy. We discuss the role of retinal pigment epithelial proliferation in age-related macular degeneration which is reparative in some cases and destructive in others. Macular retinal pigment epithelium wound repair and regression of choroidal neovascularization are more pronounced in younger than older patients. We discuss the possibility that the limited retinal pigment epithelial proliferation and latent wound repair in older age-related macular degeneration patients can be stimulated to promote disease regression in age-related macular degeneration. PMID:26041390

  10. The Association between the Lipids Levels in Blood and Risk of Age-Related Macular Degeneration

    PubMed Central

    Wang, Yafeng; Wang, Mingxu; Zhang, Xiaoqing; Zhang, Qianyu; Nie, Jing; Zhang, Ming; Liu, Xiaohong; Ma, Le

    2016-01-01

    Lipid metabolism may be involved in the pathogenic mechanism of age-related macular degeneration (AMD). However, conflicting results have been reported in the associations of AMD with blood lipids. We performed a meta-analysis including a total of 19 studies to evaluate associations between blood lipids and this disease. The result reported that the high level of high-density lipoprotein cholesterol (HDL-C) obtained with an increment of 1 mmol/L could result in a significantly increase in the AMD risk of approximately 18% (relative risk (RR), 1.18; 95% confidence interval (CI), 1.01 to 1.35; I2 = 53.8%; p = 0.007). High levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were significantly associated with a decreased risk of AMD (RRs ranging from 0.92 to 0.95; all p < 0.05). The stratified analysis based on AMD subtypes showed that these blood lipids were only significantly associated with the risk of early AMD (all p < 0.05). The association between the blood lipids and AMD risk did not differ substantially based on the other characteristics of the participants. A high HDL-C level was associated with an increased AMD risk, whereas participants with high TC, LDL-C, and TG concentrations may show a decreased risk for this disease. Further well-designed large studies are warranted to confirm the conclusions. PMID:27782072

  11. Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration.

    PubMed

    Kanemura, Hoshimi; Go, Masahiro J; Shikamura, Masayuki; Nishishita, Naoki; Sakai, Noriko; Kamao, Hiroyuki; Mandai, Michiko; Morinaga, Chikako; Takahashi, Masayo; Kawamata, Shin

    2014-01-01

    Basic studies of human pluripotential stem cells have advanced rapidly and stem cell products are now seeing therapeutic applications. However, questions remain regarding the tumorigenic potential of such cells. Here, we report the tumorigenic potential of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of wet-type, age-related macular degeneration (AMD). First, immunodeficient mouse strains (nude, SCID, NOD-SCID and NOG) were tested for HeLa cells' tumor-forming capacity by transplanting various cell doses subcutaneously with or without Matrigel. The 50% Tumor Producing Dose (TPD50 value) is the minimal dose of transplanted cells that generated tumors in 50% of animals. For HeLa cells, the TPD50 was the lowest when cells were embedded in Matrigel and transplanted into NOG mice (TPD50 = 10(1.1), n = 75). The TPD50 for undifferentiated iPSCs transplanted subcutaneously to NOG mice in Matrigel was 10(2.12); (n = 30). Based on these experiments, 1×10(6) iPSC-derived RPE were transplanted subcutaneously with Matrigel, and no tumor was found during 15 months of monitoring (n = 65). Next, to model clinical application, we assessed the tumor-forming potential of HeLa cells and iPSC 201B7 cells following subretinal transplantation of nude rats. The TPD50 for iPSCs was 10(4.73) (n = 20) and for HeLa cells 10(1.32) (n = 37) respectively. Next, the tumorigenicity of iPSC-derived RPE was tested in the subretinal space of nude rats by transplanting 0.8-1.5×10(4) iPSC-derived RPE in a collagen-lined (1 mm×1 mm) sheet. No tumor was found with iPSC-derived RPE sheets during 6-12 months of monitoring (n = 26). Considering the number of rodents used, the monitoring period, the sensitivity of detecting tumors via subcutaneous and subretinal administration routes and the incidence of tumor formation from the iPSC-derived RPE, we conclude that the tumorigenic potential of the iPSC-derived RPE was negligible.

  12. Allicin attenuates H₂O₂-induced cytotoxicity in retinal pigmented epithelial cells by regulating the levels of reactive oxygen species.

    PubMed

    Tu, Gerile; Zhang, Yu-Feng; Wei, Wei; Li, Langen; Zhang, Yanmei; Yang, Jia; Xing, Yiqiao

    2016-03-01

    Retinal pigmented epithelial cell (RPE) oxidative stress is known to have a vital role in the etiology of age‑related macular degeneration (AMD). The present study aimed to investigate whether allicin, a natural product with antioxidant activity, was able to protect RPEs (ARPE‑19) from hydrogen peroxide (H2O2)‑induced damage, and to determine the underlying mechanisms. The 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyl tetrazolium bromide assay was used to determine cellular viability, and reactive oxygen species (ROS) were detected using a ROS Assay kit. The results demonstrated that allicin was able to protect ARPE‑19 cells from H2O2‑induced damage in a dose‑dependent manner. In addition, allicin attenuated oxidative stress by reducing the levels of intracellular ROS and malondialdehyde (MDA), and enhancing the glutathione/glutathione disulfide (GSSG) ratio. With regards to the underlying mechanism, allicin was able to markedly modulate the expression levels of ROS‑associated enzymes, including superoxide dismutase, NADPH oxidase 4 and NAD(P)H dehydrogenase quinone 1, and elevate the activity of nuclear factor erythroid 2‑related factor 2 in the H2O2‑stimulated ARPE‑19 cells. These results suggested that allicin may exert protective effects against H2O2‑induced cytotoxicity in RPEs via ROS regulation. PMID:26781848

  13. Increased Macular Pigment Optical Density and Visual Acuity following Consumption of a Buttermilk Drink Containing Lutein-Enriched Egg Yolks: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    van der Made, Sanne M; Kelly, Elton R; Kijlstra, Aize; Plat, Jogchum; Berendschot, Tos T J M

    2016-01-01

    Purpose. To study the effect of 1-year daily consumption of a dairy drink containing lutein-enriched egg yolks on macular pigment optical density (MPOD) and visual function parameters in elderly subjects with ocular drusen and/or retinal pigment abnormalities. Methods. One hundred and one subjects were recruited to participate in this randomized, double-blind, placebo-controlled parallel intervention trial. Statistical analyses were performed with 46 subjects in the lutein group and 43 in the control group. MPOD, best corrected visual acuity (BCVA, logMAR), and dark adaptation were measured at the start of the study, after 6 months and after 12 months. Plasma lutein and zeaxanthin concentrations were assessed at baseline and at the end of the study. Results. In the lutein group, plasma lutein concentrations increased significantly from 205 ng/mL at baseline to 399 ng/mL after twelve months of intervention. MPOD increased significantly from 0.45 to 0.52 and BCVA improved significantly from -0.04 to -0.09 LogMar. Differences in rod dark adaptation rate between both groups were not significant. Conclusion. Daily consumption of a dairy drink containing lutein-enriched egg yolks for one year improves visual acuity, MPOD, and plasma lutein concentration in elderly subjects with drusen and/or retinal pigment epithelial abnormalities.

  14. Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration

    PubMed Central

    Marazita, Mariela C.; Dugour, Andrea; Marquioni-Ramella, Melisa D.; Figueroa, Juan M.; Suburo, Angela M.

    2015-01-01

    Oxidative stress has a critical role in the pathogenesis of Age-related Macular Degeneration (AMD), a multifactorial disease that includes age, gene variants of complement regulatory proteins and smoking as the main risk factors. Stress-induced premature cellular senescence (SIPS) is postulated to contribute to this condition. In this study, we hypothesized that oxidative damage, promoted by endogenous or exogenous sources, could elicit a senescence response in RPE cells, which would in turn dysregulate the expression of major players in AMD pathogenic mechanisms. We showed that exposure of a human RPE cell line (ARPE-19) to a cigarette smoke concentrate (CSC), not only enhanced Reactive Oxygen Species (ROS) levels, but also induced 8-Hydroxydeoxyguanosine-immunoreactive (8-OHdG) DNA lesions and phosphorylated-Histone 2AX-immunoreactive (p-H2AX) nuclear foci. CSC-nuclear damage was followed by premature senescence as shown by positive senescence associated-β-galactosidase (SA-β-Gal) staining, and p16INK4a and p21Waf-Cip1 protein upregulation. N-acetylcysteine (NAC) treatment, a ROS scavenger, decreased senescence markers, thus supporting the role of oxidative damage in CSC-induced senescence activation. ARPE-19 senescent cultures were also established by exposure to hydrogen peroxide (H2O2), which is an endogenous stress source produced in the retina under photo-oxidation conditions. Senescent cells upregulated the proinflammatory cytokines IL-6 and IL-8, the main markers of the senescence-associated secretory phenotype (SASP). Most important, we show for the first time that senescent ARPE-19 cells upregulated vascular endothelial growth factor (VEGF) and simultaneously downregulated complement factor H (CFH) expression. Since both phenomena are involved in AMD pathogenesis, our results support the hypothesis that SIPS could be a principal player in the induction and progression of AMD. Moreover, they would also explain the striking association of this disease

  15. Candidate gene study of macular response to supplemental lutein and zeaxanthin.

    PubMed

    Yonova-Doing, Ekaterina; Hysi, Pirro G; Venturini, Cristina; Williams, Katie M; Nag, Abhishek; Beatty, Stephen; Liew, S H Melissa; Gilbert, Clare E; Hammond, Christopher J

    2013-10-01

    Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism.

  16. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration.

  17. Hypotrichosis with juvenile macular dystrophy: Portuguese case.

    PubMed

    Elfatoiki, Fatima Zahra; Cordoliani, Florance; Pascal Regane, Pascal; Afforitit-Demoge, Aude

    2016-01-01

    Hypotrichosis with juvenile macular dystrophy is a rare congenital disease mainly found in the Druze population of Northern Israel. This disorder is caused by the CDH3 mutation encoding P-cadherin, which is expressed in retinal pigment epithelium and hair follicles. An 11-year-old girl who was born to related Portuguese parents, had hypotrichosis since birth and macular dystrophy diagnosed at age 5. Fundus examination and fluorescein angiography revealed located macular pigmentary abnormalities. No molecular analysis was done. A fundus examination should be considered mandatory in the assessment of congenital hypotrichosis. PMID:27617529

  18. Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: the LEVEL study

    PubMed Central

    Tolentino, Michael

    2010-01-01

    Aim To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. Methods A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30–120 days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275 μm or less or thinning of 100 μm or more (optical coherence tomography); visual acuity (VA) 20/20–20/400. Intravitreal pegaptanib 0.3 mg was administered as maintenance every 6 weeks for 48 weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration. Results Of 568 enrolled subjects, 86% completed 1 year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20 μm increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147 days after maintenance initiation). Conclusions An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD. PMID:20472746

  19. Macular Degeneration

    MedlinePlus

    ... common early symptom. Dry AMD happens when the light-sensitive cells in the macula slowly break down. Your gradually lose your central vision. A common early symptom is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease ...

  20. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain t...

  1. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    PubMed Central

    Vishwanathan, Rohini; Neuringer, Martha; Snodderly, D. Max; Schalch, Wolfgang; Johnson, Elizabeth J.

    2013-01-01

    Objectives Xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain tissue. The objective of the study was to evaluate the relationship between retinal and brain levels of these xanthophylls in non-human primates. Methods Study animals included rhesus monkeys reared on diets devoid of xanthophylls that were subsequently fed pure lutein or pure zeaxanthin (both at 3.9 μmol/kg*d, n=6/group) and normal rhesus monkeys fed a stock diet (0.26 μmol/kg*d lutein and 0.24 μmol/kg*d zeaxanthin, n=5). Retina (4 mm macular punch, 4-8 mm annulus and periphery) and brain tissue (cerebellum, frontal cortex, occipital cortex and pons) from the same animals were analyzed by reverse phase HPLC. Results Lutein in the macula and annulus were significantly related to lutein levels in the cerebellum, occipital cortex and pons, both in bivariate analysis and after adjusting for age, sex and n–3 fatty acid status. In the frontal cortex the relationship was marginally significant. Macular zeaxanthin was significantly related to zeaxanthin in the cerebellum and frontal cortex, while the relationship was marginally significant in the occipital cortex and pons in a bivariate model. Discussion An integrated measure of total macular pigment optical density, which can be measured noninvasively, has the potential to be used as a biomarker to assess brain lutein and zeaxanthin status. PMID:22780947

  2. Convergence in pigmentation at multiple levels: mutations, genes and function

    PubMed Central

    Manceau, Marie; Domingues, Vera S.; Linnen, Catherine R.; Rosenblum, Erica Bree; Hoekstra, Hopi E.

    2010-01-01

    Convergence—the independent evolution of the same trait by two or more taxa—has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels. PMID:20643733

  3. Convergence in pigmentation at multiple levels: mutations, genes and function.

    PubMed

    Manceau, Marie; Domingues, Vera S; Linnen, Catherine R; Rosenblum, Erica Bree; Hoekstra, Hopi E

    2010-08-27

    Convergence--the independent evolution of the same trait by two or more taxa--has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels. PMID:20643733

  4. Changes in localization and expression levels of Shroom2 and spectrin contribute to variation in amphibian egg pigmentation patterns.

    PubMed

    Lee, Chanjae; Le, Minh-Phuong; Cannatella, David; Wallingford, John B

    2009-06-01

    One contributing factor in the worldwide decline in amphibian populations is thought to be the exposure of eggs to UV light. Enrichment of pigment in the animal hemisphere of eggs laid in the sunlight defends against UV damage, but little is known about the cell biological mechanisms controlling such polarized pigment patterns. Even less is known about how such mechanisms were modified during evolution to achieve the array of amphibian egg pigment patterns. Here, we show that ectopic expression of the gamma-tubulin regulator, Shroom2, is sufficient to induce co-accumulation of pigment granules, spectrin, and dynactin in Xenopus blastomeres. Shroom2 and spectrin are enriched and co-localize specifically in the pigmented animal hemisphere of Xenopus eggs and blastulae. Moreover, Shroom2 messenger RNA (mRNA) is expressed maternally at high levels in Xenopus. In contrast to Xenopus, eggs and blastulae of Physalaemus pustulosus have very little surface pigmentation. Rather, we find that pigment is enriched in the perinuclear region of these embryos, where it co-localizes with spectrin. Moreover, maternal Shroom2 mRNA was barely detectable in Physaleamus, though zygotic levels were comparable to Xenopus. We therefore suggest that a Shroom2/spectrin/dynactin-based mechanism controls pigment localization in amphibian eggs and that variation in maternal Shroom2 mRNA levels accounts in part for variation in amphibian egg pigment patterns during evolution. PMID:19554350

  5. Macular degeneration (image)

    MedlinePlus

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  6. A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo

    PubMed Central

    Paun, Constantin C.; Lechanteur, Yara T. E.; Groenewoud, Joannes M. M.; Altay, Lebriz; Schick, Tina; Daha, Mohamed R.; Fauser, Sascha; Hoyng, Carel B.; den Hollander, Anneke I.; de Jong, Eiko K.

    2016-01-01

    The complement system is the first line of defense against foreign intruders, and deregulation of this system has been described in multiple diseases. In age-related macular degeneration (AMD), patients have higher complement activation levels compared to controls. Recently, a combination of three single nucleotide polymorphisms (SNPs) in genes of the complement system, referred to as a complotype, has been described to increase complement activation in vitro. Here we describe a novel complotype composed of CFB (rs4151667)-CFB (rs641153)-CFH (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10−13) and complement activation levels in vivo (p = 8.31*10−9). The most frequent genotype combination of this complotype was associated with the highest complement activation levels in both patients and controls. These findings are relevant in the context of complement-lowering treatments for AMD that are currently under development. Patients with a genetic predisposition to higher complement activation levels will potentially benefit the most of such treatments. PMID:27241480

  7. American Macular Degeneration Foundation

    MedlinePlus

    ... to content Contact DONATE Search for: Search Saving sight through research and education American Macular Degeneration Foundation Saving Sight Through Research and Education Menu About Macular Degeneration ...

  8. Macular Diplopia.

    PubMed

    Shippman, Sara; Cohen, Kenneth R; Heiser, Larissa

    2015-01-01

    Maculopathies affect point-to-point foveal correspondence causing diplopia. The effect that the maculopathies have on the interaction of central sensory fusion and peripheral fusion are different than the usual understanding of treatment for diplopia. This paper reviews the pathophysiology of macular diplopia, describes the binocular pathology causing the diplopia, discusses the clinical evaluation, and reviews the present treatments including some newer treatment techniques. PMID:26564922

  9. Macular edema. A complication of diabetic retinopathy.

    PubMed

    Ferris, F L; Patz, A

    1984-05-01

    Diabetic macular edema is the leading cause of decreased vision from diabetic retinopathy. This decreased vision is caused by an increase in extracellular fluid within the retina distorting the retinal architecture and frequently taking on a pattern of cystoid macular edema. This fluid accumulates within the retina because of the breakdown of the barriers within the retinal blood vessels and possibly the pigment epithelium. Diabetic macular edema tends to be a chronic disorder. Although spontaneous recovery is not an uncommon occurrence, over one-half of diabetics with macular edema will lose two or more lines of visual acuity within two years. The most promising treatment for diabetic macular edema has been photocoagulation. It is recommended that in all patients with diabetic macular edema attempts be made to normalize elevated blood glucose, decrease elevated blood pressure, and improve cardiac or renal status. Reduction of serum lipids by diet or pharmacologic means is an unproven treatment at this time. The Early Treatment Diabetic Retinopathy Study hopefully will provide more definitive information as to whether photocoagulation is effective in various subgroups of patients with diabetic macular edema.

  10. Genetic basis of continuous variation in the levels and modular inheritance of pigmentation in cichlid fishes.

    PubMed

    Albertson, R Craig; Powder, Kara E; Hu, Yinan; Coyle, Kaitlin P; Roberts, Reade B; Parsons, Kevin J

    2014-11-01

    Variation in pigmentation type and levels is a hallmark of myriad evolutionary radiations, and biologists have long been fascinated by the factors that promote and maintain variation in coloration across populations. Here, we provide insights into the genetic basis of complex and continuous patterns of colour variation in cichlid fishes, which offer a vast diversity of pigmentation patterns that have evolved in response to both natural and sexual selection. Specifically, we crossed two divergent cichlid species to generate an F2 mapping population that exhibited extensive variation in pigmentation levels and patterns. Our experimental design is robust in that it combines traditional quantitative trait locus (QTL) analysis with population genomics, which has allowed us to move efficiently from QTL interval to candidate gene. In total, we detected 41 QTL and 13 epistatic interactions that underlie melanocyte- and xanthophore-based coloration across the fins and flanks of these fishes. We also identified 2 QTL and 1 interaction for variation in the magnitude of integration among these colour traits. This finding in particular is notable as there are marked differences both within and between species with respect to the complexity of pigmentation patterns. While certain individuals are characterized by more uniform 'integrated' colour patterns, others exhibit many more degrees of freedom with respect to the distribution of colour 'modules' across the fins and flank. Our data reveal, for the first time, a genetic basis for this difference. Finally, we implicate pax3a as a mediator of continuous variation in the levels of xanthophore-based colour along the cichlid flank. PMID:25156298

  11. Genetic basis of continuous variation in the levels and modular inheritance of pigmentation in cichlid fishes.

    PubMed

    Albertson, R Craig; Powder, Kara E; Hu, Yinan; Coyle, Kaitlin P; Roberts, Reade B; Parsons, Kevin J

    2014-11-01

    Variation in pigmentation type and levels is a hallmark of myriad evolutionary radiations, and biologists have long been fascinated by the factors that promote and maintain variation in coloration across populations. Here, we provide insights into the genetic basis of complex and continuous patterns of colour variation in cichlid fishes, which offer a vast diversity of pigmentation patterns that have evolved in response to both natural and sexual selection. Specifically, we crossed two divergent cichlid species to generate an F2 mapping population that exhibited extensive variation in pigmentation levels and patterns. Our experimental design is robust in that it combines traditional quantitative trait locus (QTL) analysis with population genomics, which has allowed us to move efficiently from QTL interval to candidate gene. In total, we detected 41 QTL and 13 epistatic interactions that underlie melanocyte- and xanthophore-based coloration across the fins and flanks of these fishes. We also identified 2 QTL and 1 interaction for variation in the magnitude of integration among these colour traits. This finding in particular is notable as there are marked differences both within and between species with respect to the complexity of pigmentation patterns. While certain individuals are characterized by more uniform 'integrated' colour patterns, others exhibit many more degrees of freedom with respect to the distribution of colour 'modules' across the fins and flank. Our data reveal, for the first time, a genetic basis for this difference. Finally, we implicate pax3a as a mediator of continuous variation in the levels of xanthophore-based colour along the cichlid flank.

  12. Loosely coupled level sets for retinal layers and drusen segmentation in subjects with dry age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    Novosel, Jelena; Wang, Ziyuan; de Jong, Henk; Vermeer, Koenraad A.; van Vliet, Lucas J.

    2016-03-01

    Optical coherence tomography (OCT) is used to produce high-resolution three-dimensional images of the retina, which permit the investigation of retinal irregularities. In dry age-related macular degeneration (AMD), a chronic eye disease that causes central vision loss, disruptions such as drusen and changes in retinal layer thicknesses occur which could be used as biomarkers for disease monitoring and diagnosis. Due to the topology disrupting pathology, existing segmentation methods often fail. Here, we present a solution for the segmentation of retinal layers in dry AMD subjects by extending our previously presented loosely coupled level sets framework which operates on attenuation coefficients. In eyes affected by AMD, Bruch's membrane becomes visible only below the drusen and our segmentation framework is adapted to delineate such a partially discernible interface. Furthermore, the initialization stage, which tentatively segments five interfaces, is modified to accommodate the appearance of drusen. This stage is based on Dijkstra's algorithm and combines prior knowledge on the shape of the interface, gradient and attenuation coefficient in the newly proposed cost function. This prior knowledge is incorporated by varying the weights for horizontal, diagonal and vertical edges. Finally, quantitative evaluation of the accuracy shows a good agreement between manual and automated segmentation.

  13. Decreased docosahexaenoic acid levels in retina and pigment epithelium of frogs fed crickets.

    PubMed

    Chen, H; Wiegand, R D; Anderson, R E

    1992-06-01

    Whole retina, rod outer segments, and retinal pigment epithelium of frogs (Rana pipiens) fed crickets for more than 1 year had significantly lower levels of docosahexaenoic acid (22: 6n-3) than the same tissues of frogs fed crickets for less than 1 month. Decreases in 22:6n-3 levels in these tissues were compensated for by increases in the n-6 polyunsaturated fatty acids (PUFAs), primarily 22:5n-6. There were no changes in the levels of saturated, monoenoic, or dienoic acids. Analysis of diacyl phospholipid molecular species (PLMS) revealed decreases in both the 22:6(n-3)-containing dipolyenoic molecular species in phosphatidylethanolamine and phosphatidylserine, and the monopolyenoic molecular species in phosphatidylcholine. These PLMS were replaced by species containing 22:5n-6 or other n-6 PUFAs. Examination of fatty acid methyl esters of total lipids extracted from crickets revealed that less than 1 mol% fatty acids were of the n-3 family, while more than 30 mol% were of the n-6 family. Thus, frogs raised on an n-3-deficient diet have reduced levels of n-3 PUFA in their retinas, rod outer segments, and retinal pigment epithelium. Although such changes have been reported for mammals, this is the first report of the effects of n-3 deficiency on the lipids of amphibians.

  14. Embryological pigment epithelial dystrophies.

    PubMed

    François, J

    1976-01-01

    The embryological pigment epithelial dystrophies may be due, although rather rarely, to chemical factors, such as antibiotics and thalidomide, to ionizing radiation and to infectious factors, syphilis or viral infections, such as mumps, measles, varicella, or cytomegalovirus. The most frequent and the most typical dystrophy is, nevertheless, the rubella epitheliopathy with its widespread scattered black pigment deposits, found predominantly in the posterior pole, and its unaffected visual functions. The macular dystrophy associated with deaf-mutism is also often due to a maternal rubella infection.

  15. Pigmented casts.

    PubMed

    Miteva, Mariya; Romanelli, Paolo; Tosti, Antonella

    2014-01-01

    Pigmented casts have been reported with variable frequency in scalp biopsies from alopecia areata, trichotillomania, chemotherapy-induced alopecia and postoperative (pressure induced) alopecia. Their presence and morphology in other scalp disorders has not been described. The authors assessed for the presence and morphology of pigmented casts in 308 transversely bisected scalp biopsies from nonscarring and scarring alopecia, referred to the Department of Dermatology, University of Miami within a year. The pigmented casts were present in 21 of 29 cases of alopecia areata (72%), 7 of 7 cases of trichotillomania (100%), 1 case of friction alopecia, 4 of 28 cases of central centrifugal cicatricial alopecia (14%), and 4 of 4 cases of dissecting cellulitis (100%). They did not show any distinguishing features except for the morphology in trichotillomania, which included twisted, linear (zip), and "button"-like pigment aggregation. The linear arrangement was found also in friction alopecia and dissecting cellulitis. Pigmented casts in the hair canals of miniaturized/vellus hairs was a clue to alopecia areata. Pigmented casts can be observed in biopsies of different hair disorders, but they are not specific for the diagnosis. Horizontal sections allow to better assess their morphology and the follicular level of presence of pigmented casts, which in the context of the other follicular findings may be a clue to the diagnosis. PMID:23823025

  16. Inactivity of human β,β-carotene-9′,10′-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment

    PubMed Central

    Li, Binxing; Vachali, Preejith P.; Gorusupudi, Aruna; Shen, Zhengqing; Sharifzadeh, Hassan; Besch, Brian M.; Nelson, Kelly; Horvath, Madeleine M.; Frederick, Jeanne M.; Baehr, Wolfgang; Bernstein, Paul S.

    2014-01-01

    The macula of the primate retina uniquely concentrates high amounts of the xanthophyll carotenoids lutein, zeaxanthin, and meso-zeaxanthin, but the underlying biochemical mechanisms for this spatial- and species-specific localization have not been fully elucidated. For example, despite abundant retinal levels in mice and primates of a binding protein for zeaxanthin and meso-zeaxanthin, the pi isoform of glutathione S-transferase (GSTP1), only human and monkey retinas naturally contain detectable levels of these carotenoids. We therefore investigated whether or not differences in expression, localization, and activity between mouse and primate carotenoid metabolic enzymes could account for this species-specific difference in retinal accumulation. We focused on β,β-carotene-9′,10′-dioxygenase (BCO2, also known as BCDO2), the only known mammalian xanthophyll cleavage enzyme. RT-PCR, Western blot analysis, and immunohistochemistry (IHC) confirmed that BCO2 is expressed in both mouse and primate retinas. Cotransfection of expression plasmids of human or mouse BCO2 into Escherichia coli strains engineered to produce zeaxanthin demonstrated that only mouse BCO2 is an active zeaxanthin cleavage enzyme. Surface plasmon resonance (SPR) binding studies showed that the binding affinities between human BCO2 and lutein, zeaxanthin, and meso-zeaxanthin are 10- to 40-fold weaker than those for mouse BCO2, implying that ineffective capture of carotenoids by human BCO2 prevents cleavage of xanthophyll carotenoids. Moreover, BCO2 knockout mice, unlike WT mice, accumulate zeaxanthin in their retinas. Our results provide a novel explanation for how primates uniquely concentrate xanthophyll carotenoids at high levels in retinal tissue. PMID:24982131

  17. Macular Degeneration Partnership

    MedlinePlus

    AMD Macular Degeneration Partnership High Contrast Original + Font Size – Home About AMD Dry AMD Wet AMD Experience AMD Living with ... vision on a daily basis. AMD (Age Related Macular Degeneration) Partnership Listen AMD Month Public Service Announcement To ...

  18. Analysis of Risk Alleles and Complement Activation Levels in Familial and Non-Familial Age-Related Macular Degeneration

    PubMed Central

    Saksens, Nicole T. M.; Lechanteur, Yara T. E.; Verbakel, Sanne K.; Groenewoud, Joannes M. M.; Daha, Mohamed R.; Schick, Tina; Fauser, Sascha; Boon, Camiel J. F.; Hoyng, Carel B.; den Hollander, Anneke I.

    2016-01-01

    Aims Age-related macular degeneration (AMD) is a multifactorial disease, in which complement-mediated inflammation plays a pivotal role. A positive family history is an important risk factor for developing AMD. Certain lifestyle factors are shown to be significantly associated with AMD in non-familial cases, but not in familial cases. This study aimed to investigate whether the contribution of common genetic variants and complement activation levels differs between familial and sporadic cases with AMD. Methods and Results 1216 AMD patients (281 familial and 935 sporadic) and 1043 controls (143 unaffected members with a family history of AMD and 900 unrelated controls without a family history of AMD) were included in this study. Ophthalmic examinations were performed, and lifestyle and family history were documented with a questionnaire. Nine single nucleotide polymorphisms (SNPs) known to be associated with AMD were genotyped, and serum concentrations of complement components C3 and C3d were measured. Associations were assessed in familial and sporadic individuals. The association with risk alleles of the age-related maculopathy susceptibility 2 (ARMS2) gene was significantly stronger in sporadic AMD patients compared to familial cases (p = 0.017 for all AMD stages and p = 0.003 for advanced AMD, respectively). ARMS2 risk alleles had the largest effect in sporadic cases but were not significantly associated with AMD in densely affected families. The C3d/C3 ratio was a significant risk factor for AMD in sporadic cases and may also be associated with familial cases. In patients with a densely affected family this effect was particularly strong with ORs of 5.37 and 4.99 for all AMD and advanced AMD respectively. Conclusion This study suggests that in familial AMD patients, the common genetic risk variant in ARMS2 is less important compared to sporadic AMD. In contrast, factors leading to increased complement activation appear to play a larger role in patients with a

  19. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  20. Methods for analysis of photosynthetic pigments and steady-state levels of intermediates of tetrapyrrole biosynthesis.

    PubMed

    Czarnecki, Olaf; Peter, Enrico; Grimm, Bernhard

    2011-01-01

    Tetrapyrroles and carotenoids are required for many indispensable functions in photosynthesis. Tetrapyrroles are essential metabolites for photosynthesis, redox reaction, and detoxification of reactive oxygen species and xenobiotics, while carotenoids function as accessory pigments, in photoprotection and in attraction to animals. Their branched metabolic pathways of synthesis and degradation are tightly controlled to provide adequate amounts of each metabolite (carotenoids/tetrapyrroles) and to prevent accumulation of photoreactive intermediates (tetrapyrroles). Many Arabidopsis mutants and transgenic plants have been reported to show variations in steady-state levels of tetrapyrrole intermediates and contents of different carotenoid species. It is a challenging task to determine the minute amounts of these metabolites to assess the metabolic flow and the activities of both pigment-synthesising and degrading pathways, to unravel limiting enzymatic steps of these biosynthetic pathways, and to characterise mutants with accumulating intermediates. In this chapter, we present a series of methods to qualify and quantify anabolic and catabolic intermediates of Arabidopsis tetrapyrrole metabolism, and describe a common method for quantification of different plant carotenoid species. Additionally, we introduce two methods for quantification of non-covalently bound haem. The approach of analysing steady-state levels of tetrapyrrole intermediates in plants, when applied in combination with analyses of transcripts, proteins, and enzyme activities, enables the biochemical and genetic elucidation of the tetrapyrrole pathway in wild-type plants, varieties, and mutants. Steady-state levels of tetrapyrrole intermediates are only up to 1/1,000 of the amounts of the accumulating end-products, chlorophyll, and haem. Although present in very low amounts, the accumulation and availability of tetrapyrrole intermediates have major consequences on the physiology and activity of

  1. Adhesive protein-free synthetic hydrogels for retinal pigment epithelium cell culture with low ROS level.

    PubMed

    Chen, Yong Mei; Liu, Zhen Qi; Feng, Zhi Hui; Xu, Feng; Liu, Jian Kang

    2014-07-01

    Engineering of human retinal pigment epithelium (RPE) cell monolayer with low level of reactive oxygen species (ROS) is important for regenerative RPE-based therapies. However, it is still challenging to culture RPE monolayer with low ROS level on soft substrates in vitro. To address this, we developed cytocompatible hydrogels to culture human RPE cell monolayer for future use in regenerative RPE-based therapies. The cell adhesion, proliferation, monolayer formation, morphology, survival, and ROS level of human ARPE-19 cells cultured on the surfaces of negatively charged poly (2-acrylamido-2-methyl propane sulfonic sodium) (PNaAMPS) and neutral poly(N,N-dimethylacrylamide) (PDMAAm) hydrogels with different stiffness were investigated. The importance of hydrogel stiffness on the cell function was firstly highlighted on the base of determined optimal Young's modulus for cultivation of RPE cell monolayer with relatively low ROS level. The construction of RPE cell monolayer with low ROS level on the PNaAMPS hydrogel may hold great potential as promising candidates for transplantation of RPE cell monolayer-hydrogel construct into the subretinal space to repair retinal functions.

  2. Effects of low-level laser therapy, electroacupuncture, and radiofrequency on the pigmentation and skin tone of adult women

    PubMed Central

    Kim, Hee-Kyoung; Min, Kyoung-Ok; Choi, Jung-Hyun; Kim, Soon-Hee

    2016-01-01

    [Purpose] In this study, the effects of low-level laser therapy (LLLT), electroacupuncture (EA), and radiofrequency (RF), which are used in physical therapy, on the pigmentation and skin tone of adult women’s faces were investigated to provide basic data for skin interventions. [Subjects and Methods] Thirty adult females were assigned to either an LLLT group (n=10), an EA group (n=10), or an RF group (n=10). The intervention was performed in two 15-minute sessions per week for six weeks. Subjects’ skin tone and pigmentation were observed before and after the intervention. [Results] The EA group showed significant reductions in pigmentation in the left and right eye rims, as well as in the left cheek. The RF group showed significant post-intervention reductions in pigmentation under the left eye, as well as in the left and right eye rims and the left cheek. The LLLT group showed significant increases in skin tone in the forehead and both eye rims. The RF group showed significant increases in skin tone under both eyes. [Conclusion] The application of LLLT, EA, and RF had positive effects on pigmentation and skin tone of adult women’s faces. PMID:27313340

  3. Effects of low-level laser therapy, electroacupuncture, and radiofrequency on the pigmentation and skin tone of adult women.

    PubMed

    Kim, Hee-Kyoung; Min, Kyoung-Ok; Choi, Jung-Hyun; Kim, Soon-Hee

    2016-05-01

    [Purpose] In this study, the effects of low-level laser therapy (LLLT), electroacupuncture (EA), and radiofrequency (RF), which are used in physical therapy, on the pigmentation and skin tone of adult women's faces were investigated to provide basic data for skin interventions. [Subjects and Methods] Thirty adult females were assigned to either an LLLT group (n=10), an EA group (n=10), or an RF group (n=10). The intervention was performed in two 15-minute sessions per week for six weeks. Subjects' skin tone and pigmentation were observed before and after the intervention. [Results] The EA group showed significant reductions in pigmentation in the left and right eye rims, as well as in the left cheek. The RF group showed significant post-intervention reductions in pigmentation under the left eye, as well as in the left and right eye rims and the left cheek. The LLLT group showed significant increases in skin tone in the forehead and both eye rims. The RF group showed significant increases in skin tone under both eyes. [Conclusion] The application of LLLT, EA, and RF had positive effects on pigmentation and skin tone of adult women's faces. PMID:27313340

  4. Oxidative Modification in Human Hair: The Effect of the Levels of Cu (II) Ions, UV Exposure and Hair Pigmentation.

    PubMed

    Grosvenor, Anita J; Marsh, Jennifer; Thomas, Ancy; Vernon, James A; Harland, Duane P; Clerens, Stefan; Dyer, Jolon M

    2016-01-01

    Protein oxidative degradation is implicated in a wide range of deleterious effects. For human hair, this oxidative damage can lead to significant observable changes in fiber physical and visual properties. A redox proteomic approach was applied to map molecular modification in human hair proteins and correlate this modification with the abundance of copper (II) ions, the levels of UV exposure and the general level of hair pigmentation. An increase in oxidative modification was observed with increasing copper (II) ion levels, regardless of the pigmentation level. Significantly, increased protein oxidative modification was also observed to occur in both lightly and darkly pigmented hair tresses even in the absence of irradiation, albeit at lower relative levels. Modification levels increased with increased copper (II) ion concentration. This new finding indicates that the level of copper (II) ions in human hair plays a key role in mediating protein oxidation, with or without exposure to UV light. Overall, these results strongly suggest that minimization of the level of copper (II) ions in human hair will mitigate and/or slow protein oxidative modification and therefore lower overall hair damage.

  5. Ionizing radiation induced changes in phenotype, photosynthetic pigments and free polyamine levels in Vigna radiata (L.) Wilczek.

    PubMed

    Sengupta, Mandar; Chakraborty, Anindita; Raychaudhuri, Sarmistha Sen

    2013-05-01

    Effects of gamma rays on the free polyamine (PA) levels were studied in Vigna radiata (L.) Wilczek. Seeds exposed to different doses of gamma rays were checked for damage on phenotype, germination frequency and alteration in photosynthetic pigments. Free polyamine levels were estimated from seeds irradiated in dry and water imbibed conditions. Polyamine levels of seedlings grown from irradiated seeds, and irradiated seedlings from unexposed seeds were also measured. Damage caused by gamma irradiation resulted in decrease in final germination percentage and seedling height. Photosynthetic pigments decreased in a dose dependent manner as marker of stress. Polyamines decreased in irradiated dry seeds and in seedlings grown from irradiated seeds. Radiation stress induced increase in free polyamines was seen in irradiated imbibed seeds and irradiated seedlings. Response of polyamines towards gamma rays is dependent on the stage of the life cycle of the plant.

  6. Skin Pigment

    MedlinePlus

    ... Professional Version Pigment Disorders Overview of Skin Pigment Albinism Vitiligo Hyperpigmentation Melasma Melanin is the brown pigment ... dark-skinned people produce the most. People with albinism have little or no melanin and thus their ...

  7. Inflammation in age-related macular degeneration.

    PubMed

    Ozaki, Ema; Campbell, Matthew; Kiang, Anna-Sophia; Humphries, Marian; Doyle, Sarah L; Humphries, Peter

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly individuals in the developed world, affecting 30-50 million people worldwide. AMD primarily affects the macular region of the retina that is responsible for the majority of central, color and daytime vision. The presence of drusen, extracellular protein aggregates that accumulate under the retinal pigment epithelium (RPE), is a major pathological hallmark in the early stages of the disease. The end stage 'dry' and 'wet' forms of the disease culminate in vision loss and are characterized by focal degeneration of the RPE and cone photoreceptors, and choroidal neovascularization (CNV), respectively. Being a multifactorial and genetically heterogeneous disease, the pathophysiology of AMD remains unclear, yet, there is ample evidence supporting immunological and inflammatory processes. Here, we review the recent literature implicating some of these immune processes in human AMD and in animal models. PMID:24664703

  8. Accelerated Accumulation of Lipofuscin Pigments in the RPE of a Mouse Model for ABCA4-Mediated Retinal Dystrophies following Vitamin A Supplementation

    PubMed Central

    Radu, Roxana A.; Yuan, Quan; Hu, Jane; Peng, Jennifer H.; Lloyd, Marcia; Nusinowitz, Steven; Bok, Dean; Travis, Gabriel H.

    2010-01-01

    Purpose Dietary supplementation with vitamin A is sometimes prescribed as a treatment for retinitis pigmentosa, a group of inherited retinal degenerations that cause progressive blindness. Loss-of-function mutations in the ABCA4 gene are responsible for a subset of recessive retinitis pigmentosa. Other mutant alleles of ABCA4 cause the related diseases, recessive cone-rod dystrophy, and recessive Stargardt macular degeneration. Mice with a knockout mutation in the abca4 gene massively accumulate toxic lipofuscin pigments in the retinal pigment epithelium. Treatment of these mice with fenretinide, an inhibitor of vitamin A delivery to the eye, blocks formation of these toxic pigments. Here the authors tested the hypothesis that dietary supplementation with vitamin A may accelerate lipofuscin pigment formation in abca4−/− mice. Methods Wild-type and abca4−/− mice were fed normal or vitamin A–supplemented diets. Tissues from these mice were analyzed biochemically for retinoids and lipofuscin pigments. Eyes from these mice were analyzed morphologically for lipofuscin in the retinal pigment epithelium and for degeneration of photoreceptors. Visual function in these mice was analyzed by electroretinography. Results Mice that received vitamin A supplementation had dramatically higher levels of retinyl esters in the liver and retinal pigment epithelium. Lipofuscin pigments were significantly increased by biochemical and morphologic analysis in wild-type and abca4−/− mice fed the vitamin A–supplemented diet. Photoreceptor degeneration was observed in 11-month-old albino, but not pigmented, abca4−/− mice on both diets. Conclusions Vitamin A supplementation should be avoided in patients with ABCA4 mutations or other retinal or macular dystrophies associated with lipofuscin accumulation in the retinal pigment epithelium. PMID:18515570

  9. Raman detection of carotenoid pigments in the human retina

    NASA Astrophysics Data System (ADS)

    Gellermann, Werner; Ermakov, Igor V.; McClane, Robert W.; Bernstein, Paul S.

    2000-04-01

    We have used resonance Raman scattering as a novel, non- invasive, in-vivo optical technique to measure the concentration of carotenoid pigment in the human retina. Using argon laser excitation we are able to measure two strong carotenoid resonance Raman signals at 1159 and 1525 wave numbers, respectively. The required laser power levels are within the limits given by safety standards for ocular exposure. Of the approximately ten carotenoid pigment found in normal human serum, the species lutein and zeaxanthin are concentrated in high amounts in the cells of the human macula, which is an approximately 5 mm diameter area of the retina in which the visual acuity is highest. These carotenoids give the macula a characteristic yellow coloration, and it is speculated that these molecules function as filter to attenuate photochemical damage and/or image degradation under bright UV/blue light exposures. In addition, they are thought to act as free-radical scavenging antioxidants. Studies have shown that there may be a link between macular degenerative diseases, the leading cause of blindness in the elderly in the US, and the presence or absence of the carotenoids. We describe an instrument capable of measuring the macular carotenoids in human subjects in a non-invasive, rapid and quantitative way.

  10. Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study

    PubMed Central

    Osthoff, Michael; Dean, Melinda M.; Baird, Paul N.; Richardson, Andrea J.; Daniell, Mark; Guymer, Robyn H.; Eisen, Damon P.

    2015-01-01

    Background In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD. Methods MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls. Results MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (<0.5 μg/ml) was encountered less frequently in the late AMD group (35% vs 56%, p = 0.03). FCN2 and MBL2 allele frequencies were similarly distributed in early and late AMD cases compared with controls (p>0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD. Conclusions SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity. PMID:26207622

  11. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  12. Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels

    PubMed Central

    Kavanagh, David; Yu, Yi; Schramm, Elizabeth C.; Triebwasser, Michael; Wagner, Erin K.; Raychaudhuri, Soumya; Daly, Mark J.; Atkinson, John P.; Seddon, Johanna M.

    2015-01-01

    To assess a potential diagnostic and therapeutic biomarker for age-related macular degeneration (AMD), we sequenced the complement factor I gene (CFI) in 2266 individuals with AMD and 1400 without, identifying 231 individuals with rare genetic variants. We evaluated the functional impact by measuring circulating serum factor I (FI) protein levels in individuals with and without rare CFI variants. The burden of very rare (frequency <1/1000) variants in CFI was strongly associated with disease (P = 1.1 × 10−8). In addition, we examined eight coding variants with counts ≥5 and saw evidence for association with AMD in three variants. Individuals with advanced AMD carrying a rare CFI variant had lower mean FI compared with non-AMD subjects carrying a variant (P < 0.001). Further new evidence that FI levels drive AMD risk comes from analyses showing individuals with a CFI rare variant and low FI were more likely to have advanced AMD (P = 5.6 × 10−5). Controlling for covariates, low FI increased the risk of advanced AMD among those with a variant compared with individuals without advanced AMD with a rare CFI variant (OR 13.6, P = 1.6 × 10−4), and also compared with control individuals without a rare CFI variant (OR 19.0, P = 1.1 × 10−5). Thus, low FI levels are strongly associated with rare CFI variants and AMD. Enhancing FI activity may be therapeutic and measuring FI provides a screening tool for identifying patients who are most likely to benefit from complement inhibitory therapy. PMID:25788521

  13. A level-set method for pathology segmentation in fluorescein angiograms and en face retinal images of patients with age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    Mohammad, Fatimah; Ansari, Rashid; Shahidi, Mahnaz

    2013-03-01

    The visibility and continuity of the inner segment outer segment (ISOS) junction layer of the photoreceptors on spectral domain optical coherence tomography images is known to be related to visual acuity in patients with age-related macular degeneration (AMD). Automatic detection and segmentation of lesions and pathologies in retinal images is crucial for the screening, diagnosis, and follow-up of patients with retinal diseases. One of the challenges of using the classical level-set algorithms for segmentation involves the placement of the initial contour. Manually defining the contour or randomly placing it in the image may lead to segmentation of erroneous structures. It is important to be able to automatically define the contour by using information provided by image features. We explored a level-set method which is based on the classical Chan-Vese model and which utilizes image feature information for automatic contour placement for the segmentation of pathologies in fluorescein angiograms and en face retinal images of the ISOS layer. This was accomplished by exploiting a priori knowledge of the shape and intensity distribution allowing the use of projection profiles to detect the presence of pathologies that are characterized by intensity differences with surrounding areas in retinal images. We first tested our method by applying it to fluorescein angiograms. We then applied our method to en face retinal images of patients with AMD. The experimental results included demonstrate that the proposed method provided a quick and improved outcome as compared to the classical Chan-Vese method in which the initial contour is randomly placed, thus indicating the potential to provide a more accurate and detailed view of changes in pathologies due to disease progression and treatment.

  14. 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

  15. Occult Macular Dystrophy

    PubMed Central

    Sayman Muslubaş, Işıl; Arf, Serra; Hocaoğlu, Mümin; Özdemir, Hakan; Karaçorlu, Murat

    2016-01-01

    Occult macular dystrophy is an inherited macular dystrophy characterized by a progressive decline of bilateral visual acuity with normal fundus appearance, fluorescein angiogram and full-field electroretinogram. This case report presents a 20-year-old female patient with bilateral progressive decline of visual acuity for six years. Her visual acuity was 3-4/10 in both eyes. Anterior segment and fundus examination, fluorescein angiogram and full-field electroretinogram were normal. She could read all Ishihara pseudoisochromatic plates. Fundus autofluorescence imaging was normal. There was a mild central hyporeflectance on fundus infrared reflectance imaging in both eyes. Reduced foveal thickness and alterations of the photoreceptor inner and outer segment junction were observed by optical coherence tomography in both eyes. Central scotoma was also found by microperimetry and reduced central response was revealed by multifocal electroretinogram in both eyes. These findings are consistent with the clinical characteristics of occult macular dystrophy. PMID:27800268

  16. C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells

    PubMed Central

    Long, Qin; Cao, Xiaoguang; Bian, Ailing

    2016-01-01

    Complement activation, specifically complement 3 (C3) activation and C3a generation, contributes to an imbalance between angiogenic stimulation by vascular endothelial growth factor (VEGF) and angiogenic inhibition by pigment epithelial derived factor (PEDF), leading to pathological angiogenesis. This study aimed to investigate the effects of C3a and small interfering RNA (siRNA) targeting C3 on the levels of VEGF and PEDF mRNAs in human retinal pigment epithelial (RPE) cells. ARPE-19 cells were cultured in the presence of exogenous C3a at 0.1 μM and 0.3 μM C3a for 24, 48, and 72 hours. 0.1 pmol/μL duplexes of siRNA targeting C3 were applied for C3a inhibition by transfecting ARPE-19 cells for 48 hours. RT-PCR was performed to examine the level of VEGF and PEDF mRNA. A random siRNA duplex was set for control siRNA. Results demonstrated that exogenous C3a significantly upregulated VEGF and downregulated PEDF mRNA levels in cultured ARPE-19 cells, and siRNA targeting C3 transfection reversed the above changes, significantly reducing VEGF and enhancing PEDF mRNAs level in ARPE-19 cells compared to the control. The present data provided evidence that reducing C3 activation can decreases VEGF and increase PEDF mRNA level in RPE and may serve as a potential therapy in pathological angiogenesis. PMID:27747237

  17. Diabetic Macular Edema

    NASA Astrophysics Data System (ADS)

    Lobo, Conceição; Pires, Isabel; Cunha-Vaz, José

    The optical coherence tomography (OCT), a noninvasive and noncontact diagnostic method, was introduced in 1995 for imaging macular diseases. In diabetic macular edema (DME), OCT scans show hyporeflectivity, due to intraretinal and/or subretinal fluid accumulation, related to inner and/or outer blood-retinal barrier breakdown. OCT tomograms may also reveal the presence of hard exudates, as hyperreflective spots with a shadow, in the outer retinal layers, among others. In conclusion, OCT is a particularly valuable diagnostic tool in DME, helpful both in the diagnosis and follow-up procedure.

  18. X-linked recessive atrophic macular degeneration from RPGR mutation.

    PubMed

    Ayyagari, Radha; Demirci, F Yesim; Liu, Jiafan; Bingham, Eve L; Stringham, Heather; Kakuk, Laura E; Boehnke, Michael; Gorin, Michael B; Richards, Julia E; Sieving, Paul A

    2002-08-01

    We mapped a new X-linked recessive atrophic macular degeneration locus to Xp21.1-p11.4 and show allelic involvement of the gene RPGR, which normally causes severe peripheral retinal degeneration leading to global blindness. Ten affected males whom we examined had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration, emphasizing the dissociation of atrophic macular degeneration from generalized cone degenerations, including X-linked cone dystrophy (COD1). The RPGR gene nonsense mutation G-->T at open reading frame (ORF)15+1164 cosegregated with the disease and may create a donor splice site. Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies.

  19. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations.

    PubMed

    Fronk, Aaron H; Vargis, Elizabeth

    2016-01-01

    The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included. PMID:27493715

  20. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

    PubMed Central

    Fronk, Aaron H; Vargis, Elizabeth

    2016-01-01

    The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included. PMID:27493715

  1. Dependence of Photosynthetic Capacity, Photosynthetic Pigment Allocation, and Carbon Storage on Nitrogen Levels in Foliage of Aspen Stands

    NASA Technical Reports Server (NTRS)

    Middleton, Elizabeth M.; Sullivan, Joseph H.; Papagno, Andrea J.

    2000-01-01

    complexes and enzymes. In mature leaves, differences in pigment content vs. N among canopy strata were accentuated when N was expressed per unit leaf area (Mg cm (exp -2)) . However, the simplest log-linear relationship between a pigment variable and N was obtained for a ratio describing the relative allocation of photosynthetic pigment to Chl a (Chl a/[Chl b + carotenoids], microgram cm (exp -2)/ microgram cm-2) vs. %N (r (exp 2) = 0.90, n=343, P less than 0.001). Attainment of comparable A (sub max) Chl a content and relative Chl a allocation per unit N (mg cm (exp -2)) was achieved at different foliar N levels per canopy group: the lowest N requirement was for hazelnut leaves in the lowest, shaded stratum at the older, closed canopy site; the highest N requirement was in aspen leaves of the upper-most stratum at the younger, more open canopy site. These results highlight the differences in physiological responses between young and fully expanded leaves and show that sustaining those foliar constituents and processes important to C balance may require higher foliar N levels in leaves of establishing vs. mature aspen stands. There may be implications for remote-sensing assessments made for carbon balance in springtime, or over a landscape mosaic comprised of different aged stands.

  2. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... Degeneration Diagnosis: How is AMD diagnosed? Macular Degeneration Treatment: How is AMD Treated? Macular ... macular degeneration (AMD) is a deterioration or breakdown of the eye's macula. The macula is a small area in the ...

  3. [Pathopshysiological mechanisms in macular edema].

    PubMed

    Turlea, Cristian; Zolog, Ileana; Blăjan, Codruta; Roşca, C; Turlea, Magdalena; Munteanu, Mihnea; Boruga, Ovidiu

    2014-01-01

    The treatment of diabetic macular edema has known a fast development in the last 5 years where the transition from laser monotherapy to intravitreal pharmacotherapy is becoming standard practice. Intravitreal injections therapy is in a continuous development with promising positive results. The use of intratvitreal devices in the treatment of macular edema of vascular cause has become a viable alternative also in treating diabetic macular edema. Several clinical studies have revealed the superiority of intravitreal treatment versus laser monotherapy. This article is evaluating and reviewing present and future treatments used to combat diabetic macular edema. [corrected].

  4. Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?

    PubMed Central

    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. PMID:24672708

  5. 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

  6. Molecular response of chorioretinal endothelial cells to complement injury: implications for macular degeneration.

    PubMed

    Zeng, Shemin; Whitmore, S Scott; Sohn, Elliott H; Riker, Megan J; Wiley, Luke A; Scheetz, Todd E; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

    2016-02-01

    Age-related macular degeneration (AMD) is a common, blinding disease of the elderly in which macular photoreceptor cells, retinal pigment epithelium and choriocapillaris endothelial cells ultimately degenerate. Recent studies have found that degeneration of the choriocapillaris occurs early in this disease and that endothelial cell drop-out is concomitant with increased deposition of the complement membrane attack complex (MAC) at the choroidal endothelium. However, the impact of MAC injury to choroidal endothelial cells is poorly understood. To model this event in vitro, and to study the downstream consequences of MAC injury, endothelial cells were exposed to complement from human serum, compared to heat-inactivated serum, which lacks complement components. Cells exposed to complement components in human serum showed increased labelling with antibodies directed against the MAC, time- and dose-dependent cell death, as assessed by lactate dehydrogenase assay and increased permeability. RNA-Seq analysis following complement injury revealed increased expression of genes associated with angiogenesis including matrix metalloproteinase (MMP)-3 and -9, and VEGF-A. The MAC-induced increase in MMP9 RNA expression was validated using C5-depleted serum compared to C5-reconstituted serum. Increased levels of MMP9 were also established, using western blot and zymography. These data suggest that, in addition to cell lysis, complement attack on choroidal endothelial cells promotes an angiogenic phenotype in surviving cells.

  7. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    PubMed

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    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.

  8. In vivo micropathology of Best macular dystrophy with optical coherence tomography.

    PubMed

    Pianta, Michael J; Aleman, Tomas S; Cideciyan, Artur V; Sunness, Janet S; Li, Yuanyuan; Campochiaro, Betsy A; Campochiaro, Peter A; Zack, Donald J; Stone, Edwin M; Jacobson, Samuel G

    2003-02-01

    Best macular dystrophy (BMD) is an autosomal dominant retinopathy caused by mutations in the VMD2 gene that encodes a chloride channel in the basolateral membrane of the retinal pigment epithelium (RPE). BMD patients were studied using optical coherence tomography (OCT) to understand the disease process in the macula leading to vision loss. BMD patients (ages 5-61), representing four families with known VMD2 mutations, were included. OCT scans were recorded in the central retina and longitudinal reflectivity profiles were analysed. The central retina in BMD showed different OCT abnormalities at or near the level of the highly reflective deep retinal band termed the outer retina-choroid complex (ORCC). Two types of ORCC change were noted to occur either separately or together: (1) splitting with or without intervening hyporeflective areas; and (2) elevation. Longitudinal study of a BMD patient indicated that such abnormalities were dynamic and changed in type and degree with time. The pathogenetic sequence in BMD may begin with defective fluid transport across the RPE secondary to the channelopathy in the basolateral membrane. In the macula, this leads to an abnormal interface with adjacent structures at both apical and basal surfaces of the RPE. The disease process results in detachments of the neurosensory retina, such as in central serous chorioretinopathy, and sub-RPE pathology resembling some stages of age-related macular degeneration, with eventual loss of photoreceptors, inner retina and central vision.

  9. Loculated fluid. A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Macular Photocoagulation Study Reading Center.

    PubMed

    Bressler, N M; Bressler, S B; Alexander, J; Javornik, N; Fine, S L; Murphy, R P

    1991-02-01

    The Foveal Photocoagulation Study, a component of the Macular Photocoagulation Study, is designed to evaluate whether laser treatment can reduce the risk of severe visual loss in eyes with well-defined choroidal neovascular membranes associated with macular degeneration that extend through the foveal center. On one third of the 554 baseline angiograms of study patients enrolled in and whose eyes were graded in the study as of January 31, 1990, the Reading Center staff has noted an unusual pattern of hyperfluorescence in the late-transit frames that has not been described previously. This pattern, which we call "loculated fluid," consists of a well-demarcated area of hyperfluorescence that appears to represent pooling of fluorescein in a compartmentalized space anterior to the choroidal neovascular leakage. Although the loculated fluid may conform to a pattern of typical cystoid macular edema, it can also pool within an area deep to the sensory retina in a shape that does not bear any resemblance to cystoid macular edema. This pattern is important to recognize because it (1) should not be confused with the angiographic pattern or extent of choroidal neovascularization and (2) should be differentiated from a serous detachment or tear of the retinal pigment epithelium.

  10. Achondroplasia and Macular Coloboma

    PubMed Central

    Ahoor, M. H.; Amizadeh, Y.; Sorkhabi, R.

    2015-01-01

    Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia. PMID:26692730

  11. Photosynthetic Pigments in Diatoms

    PubMed Central

    Kuczynska, Paulina; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

    2015-01-01

    Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvesting pigments such as chlorophyll a, chlorophyll c, and fucoxanthin, there is a group of photoprotective carotenoids which includes β-carotene and the xanthophylls, diatoxanthin, diadinoxanthin, violaxanthin, antheraxanthin, and zeaxanthin, which are engaged in the xanthophyll cycle. Additionally, some intermediate products of biosynthetic pathways have been identified in diatoms as well as unusual pigments, e.g., marennine. Marine algae have become widely recognized as a source of unique bioactive compounds for potential industrial, pharmaceutical, and medical applications. In this review, we summarize current knowledge on diatom photosynthetic pigments complemented by some new insights regarding their physico-chemical properties, biological role, and biosynthetic pathways, as well as the regulation of pigment level in the cell, methods of purification, and significance in industries. PMID:26389924

  12. In vivo snapshot hyperspectral image analysis of age-related macular degeneration.

    PubMed

    Lee, N; Wielaard, J; Fawzi, A A; Sajda, P; Laine, A F; Martin, G; Humayun, M S; Smith, R T

    2010-01-01

    Drusen, the hallmark lesions of age related macular degeneration (AMD), are biochemically heterogeneous and the identification of their biochemical distribution is key to the understanding of AMD. Yet the challenges are to develop imaging technology and analytics, which respect the physical generation of the hyperspectral signal in the presence of noise, artifacts, and multiple mixed sources while maximally exploiting the full data dimensionality to uncover clinically relevant spectral signatures. This paper reports on the statistical analysis of hyperspectral signatures of drusen and anatomical regions of interest using snapshot hyperspectral imaging and non-negative matrix factorization (NMF). We propose physical meaningful priors as initialization schemes to NMF for finding low-rank decompositions that capture the underlying physiology of drusen and the macular pigment. Preliminary results show that snapshot hyperspectral imaging in combination with NMF is able to detect biochemically meaningful components of drusen and the macular pigment. To our knowledge, this is the first reported demonstration in vivo of the separate absorbance peaks for lutein and zeaxanthin in macular pigment.

  13. 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

  14. [Diagnostic Criteria for Atrophic Age-related Macular Degeneration].

    PubMed

    Takahashi, Kanji; Shiraga, Fumio; Ishida, Susumu; Kamei, Motohiro; Yanagi, Yasuo; Yoshimura, Nagahisa

    2015-10-01

    Diagnostic criteria for dry age-related macular degeneration is described. Criteria include visual acuity, fundscopic findings, diagnostic image findings, exclusion criteria and classification of severity grades. Essential findings to make diagnosis as "geographic atrophy" are, 1) at least 250 μm in diameter, 2) round/oval/cluster-like or geographic in shape, 3) sharp delineation, 4) hypopigmentation or depigmentation in retinal pigment epithelium, 5) choroidal vessels are more visible than in surrounding area. Severity grades were classified as mild, medium and severe by relation of geographic atrophy to the fovea and attendant findings. PMID:26571627

  15. 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

  16. Expression of human complement factor H prevents age-related macular degeneration-like retina damage and kidney abnormalities in aged Cfh knockout mice.

    PubMed

    Ding, Jin-Dong; Kelly, Una; Landowski, Michael; Toomey, Christopher B; Groelle, Marybeth; Miller, Chelsey; Smith, Stephanie G; Klingeborn, Mikael; Singhapricha, Terry; Jiang, Haixiang; Frank, Michael M; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh(-/-)) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh(-/-) mice, and transgenics had a thicker outer nuclear layer and less sub-retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets.

  17. Expression of Human Complement Factor H Prevents Age-Related Macular Degeneration–Like Retina Damage and Kidney Abnormalities in Aged Cfh Knockout Mice

    PubMed Central

    Ding, Jin-Dong; Kelly, Una; Landowski, Michael; Toomey, Christopher B.; Groelle, Marybeth; Miller, Chelsey; Smith, Stephanie G.; Klingeborn, Mikael; Singhapricha, Terry; Jiang, Haixiang; Frank, Michael M.; Bowes Rickman, Catherine

    2016-01-01

    Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh−/−) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh−/− mice, and transgenics had a thicker outer nuclear layer and less sub–retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets. PMID:25447048

  18. Progressive macular hypomelanosis: an overview.

    PubMed

    Relyveld, Germaine N; Menke, Henk E; Westerhof, Wiete

    2007-01-01

    Progressive macular hypomelanosis (PMH) is a common skin disorder that is often misdiagnosed. Various authors have written about similar skin disorders, referring to them by different names, but we believe that all these similar disorders are part of the same entity.PMH is characterized by ill-defined nummular, non-scaly hypopigmented spots on the trunk, often confluent in and around the midline, and rarely extending to the proximal extremities and neck/head region. There is no itch, pain, or preceding inflammation. PMH has a worldwide distribution; however, it is more often identified in Black people living in or originating from tropical countries. It is also more often seen in young females. The natural history of PMH is stable disease or perhaps slow progression over decades, with spontaneous disappearance after mid-life. Extensive pityriasis alba is probably identical with PMH and we suggest discontinuation of use of the former term on the grounds that extensive pityriasis alba is histologically and clinically different from classical pityriasis alba, which is basically an eczematous type of disorder.PMH is characterized histologically by diminished pigment in the epidermis and a normal-looking dermis. Electron microscopy shows a shift from large melanosomes in normal-looking skin to small aggregated, membrane-bound melanosomes in hypopigmented skin. PMH should be differentiated from other disorders with hypopigmentation on the trunk such as pityriasis versicolor. We propose that Propionibacterium acnes bacteria living in hair follicles are the cause of PMH as a result of production of a hypothetical depigmenting factor. This hypothesis is based on: (i) the presence of a red follicular fluorescence in the hypopigmented spots and the absence of this phenomenon in normal skin when examined under a Wood's light in a dark room; (ii) cultivation of P. acnes from the follicles in the hypopigmented spots but not from follicles in normal-looking skin; and (iii

  19. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

    PubMed

    Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Zeng, Shemin; Braun, Terry A; Mullins, Robert F; Scheetz, Todd E

    2014-12-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  20. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

    PubMed Central

    Whitmore, S. Scott; Wagner, Alex H.; DeLuca, Adam P.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Zeng, Shemin; Braun, Terry A.; Mullins, Robert F.; Scheetz, Todd E.

    2014-01-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  1. Macular morphology and response to ranibizumab treatment in patients with wet age-related macular degeneration

    PubMed Central

    Dervenis, Nikolaos; Younis, Saad

    2016-01-01

    Purpose The purpose of this study was to assess whether specific characteristics of spectral domain optical coherence tomography (SD-OCT) affect structural and functional outcomes and number of injections needed in ranibizumab (0.05 mL of 10 mg/mL Lucentis solution)-treated wet age-related macular degeneration (AMD) patients. Patients and methods This retrospective case series included 62 newly diagnosed wet AMD patients treated with three monthly intravitreal ranibizumab injections followed by monthly follow-up and pro re nata retreatment. The presence of dome-shaped pigment epithelial detachment (PED), disruption of the retinal pigment epithelium (RPE), and subretinal and intraretinal fluid was associated with changes in Early Treatment of Diabetic Retinopathy Study visual acuity, central macular thickness (CMT), and number of injections needed during the 6-month follow-up. Results The presence of PED was associated with lower values of CMT at presentation (399 μm [±132 μm] vs 310 μm [±51 μm], P=0.005). The presence of RPE disruption was associated with worse visual acuity in month 6 (0.36 [±0.22] vs 0.61 [0.45], P=0.027) and fewer injections (4.23 [±0.92] vs 3.55 [±0.60], P=0.007). The presence of intraretinal fluid at presentation was associated with worse visual acuity outcomes in month 4 (P=0.045) but not in month 6. Conclusion The dome-shaped PED was associated with lower CMT at presentation, but it did not affect response to treatment. RPE disruption was associated with worse functional outcomes with fewer injections. Intraretinal fluid at presentation may suggest delayed response to treatment. Individualized SD-OCT analysis could lead to individualized approach to wet AMD patients. SD-OCT can offer imaging biomarkers to assess the prognosis of anti-VEGF treatment in AMD patients. PMID:27366051

  2. Ziv-aflibercept in macular disease

    PubMed Central

    Mansour, Ahmad M; Al-Ghadban, Sara I; Yunis, Muhammad H; El-Sabban, Marwan E

    2015-01-01

    Background/aims Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis. Methods Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA. Results There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab. Conclusions Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept. Trial registration number NCT02173873. PMID:25677668

  3. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

  4. Proline levels, oxidative metabolism and photosynthetic pigments during in vitro growth and acclimatization of Pitcairnia encholirioides L.B. Sm. (Bromeliaceae).

    PubMed

    Resende, C F; Braga, V F; Pereira, P F; Silva, C J; Vale, V F; Bianchetti, R E; Forzza, R C; Ribeiro, C; Peixoto, P H P

    2016-02-01

    This study aimed to evaluate the variation in the levels of proline, oxidative metabolism and photosynthetic pigments in plants of Pitcairnia encholirioides grown in vitro under different conditions and after acclimatization. The analyses were performed after 150 days of in vitro cultivation in MS media supplemented with 10 µM GA3 or 0.2 µM NAA, sucrose at 15 or 30 g L-1, in test tubes which allowed gas exchange or in a hermetically sealed system, and 180 days after acclimatization. The in vitro maintenance in hermetically sealed flasks, with GA3 and 15 g L-1 sucrose had adverse metabolic effects, which was demonstrated by the lower proline and photosynthetic pigments accumulation and by the increase in antioxidant enzymes activities. After acclimatization, differences for proline and photosynthetic pigments were no longer found and the enzymatic activities ranged unevenly. The results suggest that the in vitro cultivation in media with 0.2 µM NAA and 30 g L-1 sucrose, in test tubes capped with closures which allowed gas exchange, is more suitable for micropropagation of P. encholirioides, providing a prolonged maintenance of in vitro cultures and plantlets with superior quality for ex vitro development.

  5. Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity

    PubMed Central

    Saksens, Nicole T.M.; Krebs, Mark P.; Schoenmaker-Koller, Frederieke E.; Hicks, Wanda; Yu, Minzhong; Shi, Lanying; Rowe, Lucy; Collin, Gayle B.; Charette, Jeremy R.; Letteboer, Stef J.; Neveling, Kornelia; van Moorsel, Tamara W.; Abu-Ltaif, Sleiman; De Baere, Elfride; Walraedt, Sophie; Banfi, Sandro; Simonelli, Francesca; Cremers, Frans P.M.; Boon, Camiel J.F.; Roepman, Ronald; Leroy, Bart P.; Peachey, Neal S.; Hoyng, Carel B.; Nishina, Patsy M.; den Hollander, Anneke I.

    2015-01-01

    Butterfly-shaped pigment dystrophy is an eye disease characterized by lesions in the macula that can resemble the wings of a butterfly. Here, we report the identification of heterozygous missense mutations in the α-catenin 1 (CTNNA1) gene in three families with butterfly-shaped pigment dystrophy. In addition, we identified a Ctnna1 missense mutation in a chemically induced mouse mutant, tvrm5. Parallel clinical phenotypes were observed in the retinal pigment epithelium (RPE) of individuals with butterfly-shaped pigment dystrophy and in tvrm5 mice, including pigmentary abnormalities, focal thickening and elevated lesions, and decreased light-activated responses. Morphological studies in tvrm5 mice revealed increased cell shedding and large multinucleated RPE cells, suggesting defects in intercellular adhesion and cytokinesis. This study identifies CTNNA1 gene variants as a cause of macular dystrophy, suggests that CTNNA1 is involved in maintaining RPE integrity, and suggests that other components that participate in intercellular adhesion may be implicated in macular disease. PMID:26691986

  6. The 3895-bp mitochondrial DNA deletion in the human eye: a potential involvement in corneal ageing and macular degeneration.

    PubMed

    Gendron, Sébastien P; Bastien, Nathalie; Mallet, Justin D; Rochette, Patrick J

    2013-03-01

    In human skin, the 3895-bp deletion of mitochondrial DNA (mtDNA(3895)) is catalysed by ultraviolet (UV) light through the generation of reactive oxygen species. Given its function in vision, the human eye is exposed to oxidising UV and blue light in its anterior (cornea, iris) and posterior (retina) structures. In this study, we employed a highly sensitive quantitative PCR technique to determine mtDNA(3895) occurrence in human eye. Our analysis shows that the mtDNA(3895) is concentrated in both the cornea and the retina. Within the cornea, the highest mtDNA(3895) level is found in the stroma, the cellular layer conferring transparency and rigidity to the human cornea. Moreover, mtDNA(3895) accumulates with age in the stroma, suggesting a role of this deletion in corneal ageing. Within the retina, mtDNA(3895) is concentrated in the macular region of both the neural retina and the retinal pigment epithelium, supporting the hypothesis that this deletion is implicated in retinal pathologies such as age-related macular degenerescence. Taken together, our results imply that UV and blue light catalyse mtDNA(3895) induction in the human eye.

  7. Mechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks

    PubMed Central

    Parmeggiani, Francesco; Sorrentino, Francesco S.; Romano, Mario R.; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Nadai, Katia; Bonomo Roversi, Elia; Franceschelli, Paola; Sebastiani, Adolfo

    2013-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation) and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis) can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch's membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease. PMID:24369445

  8. Down-regulation of flavonoid 3'-hydroxylase gene expression by virus-induced gene silencing in soybean reveals the presence of a threshold mRNA level associated with pigmentation in pubescence.

    PubMed

    Nagamatsu, Atsushi; Masuta, Chikara; Matsuura, Hideyuki; Kitamura, Keisuke; Abe, Jun; Kanazawa, Akira

    2009-01-01

    Changes in flavonoid content are often manifested as altered pigmentation in plant tissues. Two loci have been identified as controlling pigmentation in soybean pubescence. Of these, the T locus appears to encode flavonoid 3'-hydroxylase (F3'H) protein: the T and t alleles are associated with tawny and gray colors, respectively, in pubescence. We previously down-regulated F3'H gene expression by virus-induced gene silencing (VIGS) in soybean. Despite this successful VIGS, the tawny pubescence pigmentation proved to be unchanged in greenhouse-grown plants. We hypothesized that the reduced mRNA level of the F3'H gene resulting from VIGS remained high enough to induce pigmentation. To verify this hypothesis, in the present study, we performed F3'H VIGS on plants grown under controlled conditions, in which the steady-state mRNA level of the F3'H gene was reduced to approximately 5% of that of greenhouse-grown plants. This VIGS treatment resulted in the loss of tawny pigmentation in pubescence, suggesting that the sf3'h1 gene is involved in the control of pigmentation in pubescence. We detected a marked decrease in target mRNA, an accumulation of short interfering RNAs (siRNAs), and a decrease in quercetin content relative to kaempferol in leaf tissues, indicating that sequence-specific mRNA degradation of the F3'H gene was induced. These results suggest that leaf tissues have a threshold mRNA level of the F3'H gene, which is associated with the occurrence of tawny pigmentation in pubescence. The estimated threshold mRNA level for pigmentation in pubescence was approximately 3% of the steady-state mRNA level of the F3'H gene in greenhouse-grown plants.

  9. The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway

    PubMed Central

    Eidet, J. R.; Reppe, S.; Pasovic, L.; Olstad, O. K.; Lyberg, T.; Khan, A. Z.; Fostad, I. G.; Chen, D. F.; Utheim, T. P.

    2016-01-01

    Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin’s potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated. PMID:26940175

  10. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    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). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  11. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

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

    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). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up 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. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  12. 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…

  13. Non-invasive in vivo measurement of macular carotenoids

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2009-01-01

    A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.

  14. [Change in biochemical composition of amaranth leaves as a result of selection for increased level of amaranthine pigment].

    PubMed

    Gins, M S; Gins, V K; Kononkov, P F

    2002-01-01

    The composition and content of secondary compounds produced by the shikimate pathway and the contents of protein and cellulose were determined in leaves of amaranth (Amaranthus tricolor L.) K-99 and the cultivar Valentina raised from it by family selection and enriched in the pigment amaranthine. It was found that intense biosynthesis of amaranthine, tyrosine, and phenylalanine resulted in a decrease in the contents of lignin, protein, and cellulose in leaves of Valentina by comparison with K-99 and in changed the morphological traits: color deepening and a decrease in leaf density. It is concluded that amaranth biosynthesis is related to nitrogen metabolism and amaranthine is an intermediate involved in conversion of nitrogen compounds in the cell.

  15. Macular posterior pigmentary incontinence: its relation to macular amyloidosis and notalgia paresthetica.

    PubMed

    Westermark, P; Ridderström, E; Vahlquist, A

    1996-07-01

    Patients with clinical features of dorsal macular amyloidosis but without subepidermal amyloid deposits were followed for 2-11 years. The clinical appearance was fairly stable during this period of time, with little tendency of healing. Only 2 of the patients developed typical macular amyloidosis during the follow-up. It is concluded that a condition strongly resembling macular amyloidosis but without amyloid is an entity, and the designation "macular posterior pigmentary incontinence" is proposed. The relationship between macular posterior pigmentary incontinence and the two conditions macular amyloidosis and notalgia paresthetica is discussed. PMID:8869690

  16. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  17. Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration

    PubMed Central

    Ueda, Keiko; Zhao, Jin; Kim, Hye Jin; Sparrow, Janet R.

    2016-01-01

    Adducts of retinaldehyde (bisretinoids) form nonenzymatically in photoreceptor cells and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin; these fluorophores are implicated in the pathogenesis of inherited and age-related macular degeneration (AMD). Here we demonstrate that bisretinoid photodegradation is ongoing in the eye. High-performance liquid chromatography (HPLC) analysis of eyes of dark-reared and cyclic light-reared wild-type mice, together with comparisons of pigmented versus albino mice, revealed a relationship between intraocular light and reduced levels of the bisretinoids A2E and A2-glycero-phosphoethanolamine (A2-GPE). Analysis of the bisretinoids A2E, A2-GPE, A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE), and all-trans-retinal dimer-phosphatidylethanolamine (all-trans-retinal dimer-PE) also decreases in albino Abca4−/− mice reared in cyclic light compared with darkness. In albino Abca4−/− mice receiving a diet supplemented with the antioxidant vitamin E, higher levels of RPE bisretinoid were evidenced by HPLC analysis and quantitation of fundus autofluorescence; this effect is consistent with photooxidative processes known to precede bisretinoid degradation. Amelioration of outer nuclear layer thinning indicated that vitamin E treatment protected photoreceptor cells. Conversely, in-cage exposure to short-wavelength light resulted in reduced fundus autofluorescence, decreased HPLC-quantified A2E, outer nuclear layer thinning, and increased methylglyoxal (MG)-adducted protein. MG was also released upon bisretinoid photodegradation in cells. We suggest that the lower levels of these diretinal adducts in cyclic light-reared and albino mice reflect photodegradative loss of bisretinoid. These mechanisms may underlie associations among AMD risk, oxidative mechanisms, and lifetime light exposure. PMID:27274068

  18. Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration.

    PubMed

    Ueda, Keiko; Zhao, Jin; Kim, Hye Jin; Sparrow, Janet R

    2016-06-21

    Adducts of retinaldehyde (bisretinoids) form nonenzymatically in photoreceptor cells and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin; these fluorophores are implicated in the pathogenesis of inherited and age-related macular degeneration (AMD). Here we demonstrate that bisretinoid photodegradation is ongoing in the eye. High-performance liquid chromatography (HPLC) analysis of eyes of dark-reared and cyclic light-reared wild-type mice, together with comparisons of pigmented versus albino mice, revealed a relationship between intraocular light and reduced levels of the bisretinoids A2E and A2-glycero-phosphoethanolamine (A2-GPE). Analysis of the bisretinoids A2E, A2-GPE, A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE), and all-trans-retinal dimer-phosphatidylethanolamine (all-trans-retinal dimer-PE) also decreases in albino Abca4(-/-) mice reared in cyclic light compared with darkness. In albino Abca4(-/-) mice receiving a diet supplemented with the antioxidant vitamin E, higher levels of RPE bisretinoid were evidenced by HPLC analysis and quantitation of fundus autofluorescence; this effect is consistent with photooxidative processes known to precede bisretinoid degradation. Amelioration of outer nuclear layer thinning indicated that vitamin E treatment protected photoreceptor cells. Conversely, in-cage exposure to short-wavelength light resulted in reduced fundus autofluorescence, decreased HPLC-quantified A2E, outer nuclear layer thinning, and increased methylglyoxal (MG)-adducted protein. MG was also released upon bisretinoid photodegradation in cells. We suggest that the lower levels of these diretinal adducts in cyclic light-reared and albino mice reflect photodegradative loss of bisretinoid. These mechanisms may underlie associations among AMD risk, oxidative mechanisms, and lifetime light exposure. PMID:27274068

  19. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration.

    PubMed

    Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

    2015-02-01

    Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1(-/-) mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1(-/-) mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1(-/-) mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD.

  20. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration

    PubMed Central

    Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

    2015-01-01

    Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1−/− mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1−/− mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1−/− mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD. PMID:25604058

  1. Cystoid Macular Edema in Bietti's Crystalline Retinopathy

    PubMed Central

    2014-01-01

    A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole. PMID:24949209

  2. [Therapeutic approach in persistent diabetic macular edema].

    PubMed

    Brănişteanu, Daniel; Moraru, Andreea

    2014-01-01

    Terminology of persistent diabetic macular edema has been initially reserved to cases unresponsive to conventional laser photocoagulation according to ETDRS criteria. While knowledge about pathophysiology of macular edema evolved and new drugs became available, the terminology of persistent diabetic macular edema expanded to include resistance to most current therapies. The purpose of this paper is to review medical and surgical options in the treatment of such difficult cases according to literature data and personal experience.

  3. The effect of high and very low fluorescent light exposure levels on age-related cataract in a pigmented mouse strain.

    PubMed

    Wolf, N S; Penn, P E

    2001-07-01

    This study examined the effect of fluorescent light on the timing and severity of age-related cataracts in a fully pigmented mouse strain, the (C57BL/6 x C3H)F1, that normally develops slowly progressing age-related cataracts only beyond middle age. Two groups of 56 animals each were exposed, respectively, either to a daily range of 66-222 foot candles (FC) or to 1 FC of standard fluorescent lighting for a period beginning at 5 weeks of age and ending at 33.5 months (by which time approximately 65% of the colony had died). Contrary to previous reports involving albino rats or mice and a strain of pigmented but cataract-prone transgenic mice, the two groups of animals in this experiment did not differ for cataract development in time of first occurrence, rate of advancement, or degree of severity. It was concluded that genetic predisposition, based on levels of oxidative free radical production vs antioxidant enzyme and repair enzyme protection in the lens, was probably the major factor governing the rate and degree of age-related cataract development in these animals. The effect of relatively intense life-long fluorescent light exposure was so minimal as not to be manifested in this strain of mice under the conditions of this experiment. Remarkably, maintaining the one group of mice in semi-darkness from 5 weeks of age to beyond their mean lifespans did nothing to delay or reduce the incidence or severity of their age-related cataracts. PMID:11428861

  4. Intrachoroidal Neovascularization in Transgenic Mice Overexpressing Vascular Endothelial Growth Factor in the Retinal Pigment Epithelium

    PubMed Central

    Schwesinger, Catherine; Yee, Charles; Rohan, Richard M.; Joussen, Antonia M.; Fernandez, Antonio; Meyer, Tobias N.; Poulaki, Vassiliki; Ma, Joseph J. K.; Redmond, T. Michael; Liu, Suyan; Adamis, Anthony P.; D’Amato, Robert J.

    2001-01-01

    Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch’s membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE65 promoter) coupled to murine VEGF164 cDNA with a rabbit β-globin-3′ UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch’s membrane. These results support the hypothesis that additional insults to the integrity of Bruch’s membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth. PMID:11238064

  5. Molecular pathology of age-related macular degeneration

    PubMed Central

    Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

    2009-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

  6. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD.

  7. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD. PMID:27688828

  8. [OCT angiography for exudative age-related macular degeneration : Initial experiences].

    PubMed

    Lommatzsch, A; Farecki, M-L; Book, B; Heimes, B; Pauleikhoff, D

    2016-01-01

    The new technique of optical coherence tomography (OCT) angiography allows a non-invasive reconstruction of the three-dimensional structure of the total retinal and choroidal vascularization within seconds. There are still limitations caused by movement artefacts, superimposition of superficial retinal vessels at the retinal pigment epithelium (RPE) level and insufficient three-dimensional imaging modalities. Initial experiences with this new method and especially the correlation with the current standard diagnostic procedure of fluorescein angiography show that new information can be obtained regarding specific vascular and neovascular changes. For three-dimensional neovascular changes, such as those found in exudative age-related macular degeneration (AMD,) a more sophisticated diagnostic analysis strategy must be specifically developed. Initial experiences demonstrate that the differentiation into the various types of choroidal neovascularization (CNV) by fluorescein angiography, specifically for type 1 (occult) and type 2 (classical) can also be visualized by OCT angiography. Furthermore, the new technology provides additional information on the choroidal and outer retinal changes associated with this disease, which may result in a better understanding of the underlying pathology. PMID:26743785

  9. Comparison of macular versus paramacular retinal sensitivity to femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Cain, Clarence P.; Toth, Cynthia A.; Thomas, Robert J.; Noojin, Gary D.; Carothers, Val; Stolarski, David J.; Rockwell, Benjamin A.

    2000-07-01

    Single 130 fs laser pulses in the near-IR (800 nm) were used to create ophthalmoscopically viewed minimum visible lesions (MVLs) within the macular and paramacular regions in rhesus monkey eyes. MVL thresholds at 1 and 24 h are reported as the 50% probability for damage (ED50) together with their fiducial limits at the 95% confidence level. These measured thresholds are compared with previously reported thresholds for near-IR and visible wavelengths for both macular and paramacular areas. Threshold doses were lower at the 24 h reading than at the 1 h reading for both retinal regions and the ED50s for the macular were slightly lower than for the paramacula. We measured the 24 h MVL ED50 thresholds to be 0.35 and 0.55 (mu) J for the macular and paramacular areas, respectively. The combined data for both areas yielded a threshold of 0.45 (mu) J.

  10. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia

    PubMed Central

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E.; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  11. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    PubMed

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  12. Arginine-Restricted Therapy Resistant Bilateral Macular Edema Associated with Gyrate Atrophy.

    PubMed

    Doguizi, Sibel; Sekeroglu, Mehmet Ali; Anayol, Mustafa Alpaslan; Yilmazbas, Pelin

    2015-01-01

    Introduction. Gyrate atrophy is a rare genetical metabolic disorder affecting vision. Here, we report a 9-year-old boy with gyrate atrophy associated with bilateral macular edema at the time of diagnosis and the effect of long term metabolic control on macular edema. Case Presentation. A 9-year-old boy presented with a complaint of low visual acuity (best corrected visual acuity: 20/80 in both eyes, refractive error: -12.00 D). Dilated fundus examination revealed multiple bilateral, sharply defined, and scalloped chorioretinal atrophy areas in the midperipheral and peripheral zone. Spectral-domain optical coherence tomography revealed bilateral cystoid macular edema in both eyes. Serum ornithine level was high (622 μmol/L). An arginine-restricted diet reduced serum ornithine level (55 μmol/L). However, visual findings including macular edema remained unchanged in 2 years of follow-up. Conclusion. Arginine-restricted diet did not improve macular edema in our patient with gyrate atrophy. A more comprehensive understanding of the underlying factors for macular edema will lead to the development of effective therapies.

  13. Angiopoietin-like Protein 2 Is a Multistep Regulator of Inflammatory Neovascularization in a Murine Model of Age-related Macular Degeneration.

    PubMed

    Hirasawa, Manabu; Takubo, Keiyo; Osada, Hideto; Miyake, Seiji; Toda, Eriko; Endo, Motoyoshi; Umezawa, Kazuo; Tsubota, Kazuo; Oike, Yuichi; Ozawa, Yoko

    2016-04-01

    Choroidal neovascularization (CNV) is a pathogenic process of age-related macular degeneration, a vision-threatening disease. The retinal pigment epithelium and macrophages both influence CNV development. However, the underlying mechanisms remain obscure. Here, we focus on Angptl2 (angiopoietin-like protein 2), a cytokine involved in age-related systemic diseases. Angptl2 was originally identified as an adipocytokine and is also expressed in the eye. Using a laser-induced CNV model, we found thatAngptl2KO mice exhibited suppressed CNV development with reduced macrophage recruitment and inflammatory mediator induction. The mediators monocyte chemotactic protein-1, interleukin-1β (Il-1β),Il-6, matrix metalloprotease-9 (Mmp-9), and transforming growth factor-β1 (Tgf-β1) that were up-regulated during CNV development were all suppressed in the retinal pigment epithelium-choroid of CNV models generated in theAngptl2KO mice. Bone marrow transplantation using wild-type and KO mice suggested that both bone marrow-derived and host-derived Angptl2 were responsible for macrophage recruitment and CNV development. Peritoneal macrophages derived fromAngptl2KO mice expressed lower levels of the inflammatory mediators. In the wild-type peritoneal macrophages and RAW264.7 cells, Angptl2 induced the mediators via integrins α4 and β2, followed by the downstream activation of NF-κB and ERK. The activation of NF-κB and ERK by Angptl2 also promoted macrophage migration. Therefore, Angptl2 from focal tissue might trigger macrophage recruitment, and that from recruited macrophages might promote expression of inflammatory mediators including Angptl2 in an autocrine and/or paracrine fashion to facilitate CNV development. Angptl2 might therefore represent a multistep regulator of CNV pathogenesis and serve as a new therapeutic target for age-related macular degeneration.

  14. 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

  15. Skin Pigmentation Disorders

    MedlinePlus

    ... skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or unhealthy, it affects melanin production. Some pigmentation disorders affect just patches of ...

  16. Classification of wet aged related macular degeneration using optical coherence tomographic images

    NASA Astrophysics Data System (ADS)

    Haq, Anam; Mir, Fouwad Jamil; Yasin, Ubaid Ullah; Khan, Shoab A.

    2013-12-01

    Wet Age related macular degeneration (AMD) is a type of age related macular degeneration. In order to detect Wet AMD we look for Pigment Epithelium detachment (PED) and fluid filled region caused by choroidal neovascularization (CNV). This form of AMD can cause vision loss if not treated in time. In this article we have proposed an automated system for detection of Wet AMD in Optical coherence tomographic (OCT) images. The proposed system extracts PED and CNV from OCT images using segmentation and morphological operations and then detailed feature set are extracted. These features are then passed on to the classifier for classification. Finally performance measures like accuracy, sensitivity and specificity are calculated and the classifier delivering the maximum performance is selected as a comparison measure. Our system gives higher performance using SVM as compared to other methods.

  17. Age-related macular degeneration and the role of the complement system.

    PubMed

    McHarg, Selina; Clark, Simon J; Day, Anthony J; Bishop, Paul N

    2015-09-01

    Age-related macular degeneration (AMD) is a leading cause of visual impairment. It is characterised by damage to a tissue complex composed of the retinal pigment epithelium, Bruch's membrane and choriocapillaris. In early AMD extracellular debris including drusen accumulates in Bruch's membrane and then in late AMD geographic atrophy and/or neovascularisation develop. Variants in genes encoding components of the alternative pathway of the complement cascade have a major influence on AMD risk, especially at the RCA locus on chromosome 1, which contains CFH and the CFHR genes. Immunohistochemical studies have demonstrated complement components in unaffected and AMD macular tissue. Whilst other factors, including oxidative stress, play important roles in AMD pathogenesis, evidence for the central role played by complement dysregulation is discussed in this review.

  18. Oral pigmentation: A review

    PubMed Central

    Sreeja, C.; Ramakrishnan, K.; Vijayalakshmi, D.; Devi, M.; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  19. Oral pigmentation: A review.

    PubMed

    Sreeja, C; Ramakrishnan, K; Vijayalakshmi, D; Devi, M; Aesha, I; Vijayabanu, B

    2015-08-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  20. Origins and consequences of hyperosmolar stress in retinal pigmented epithelial cells.

    PubMed

    Willermain, François; Libert, Sarah; Motulsky, Elie; Salik, Dany; Caspers, Laure; Perret, Jason; Delporte, Christine

    2014-01-01

    The retinal pigmented epithelium (RPE) is composed of retinal pigmented epithelial cells joined by tight junctions and represents the outer blood-retinal barrier (BRB). The inner BRB is made of endothelial cells joined by tight junctions and glial extensions surrounding all the retinal blood vessels. One of the functions of the RPE is to maintain an osmotic transepithelial gradient created by ionic pumps and channels, avoiding paracellular flux. Under such physiological conditions, transcellular water movement follows the osmotic gradient and flows normally from the retina to the choroid through the RPE. Several diseases, such as diabetic retinopathy, are characterized by the BRB breakdown leading to leakage of solutes, proteins, and fluid from the retina and the choroid. The prevailing hypothesis explaining macular edema formation during diabetic retinopathy incriminates the inner BRB breakdown resulting in increased osmotic pressure leading in turn to massive water accumulation that can affect vision. Under these conditions, it has been hypothesized that RPE is likely to be exposed to hyperosmolar stress at its apical side. This review summarizes the origins and consequences of osmotic stress in the RPE. Ongoing and further research advances will clarify the mechanisms, at the molecular level, involved in the response of the RPE to osmotic stress and delineate potential novel therapeutic targets and tools.

  1. Origins and consequences of hyperosmolar stress in retinal pigmented epithelial cells

    PubMed Central

    Willermain, François; Libert, Sarah; Motulsky, Elie; Salik, Dany; Caspers, Laure; Perret, Jason; Delporte, Christine

    2014-01-01

    The retinal pigmented epithelium (RPE) is composed of retinal pigmented epithelial cells joined by tight junctions and represents the outer blood-retinal barrier (BRB). The inner BRB is made of endothelial cells joined by tight junctions and glial extensions surrounding all the retinal blood vessels. One of the functions of the RPE is to maintain an osmotic transepithelial gradient created by ionic pumps and channels, avoiding paracellular flux. Under such physiological conditions, transcellular water movement follows the osmotic gradient and flows normally from the retina to the choroid through the RPE. Several diseases, such as diabetic retinopathy, are characterized by the BRB breakdown leading to leakage of solutes, proteins, and fluid from the retina and the choroid. The prevailing hypothesis explaining macular edema formation during diabetic retinopathy incriminates the inner BRB breakdown resulting in increased osmotic pressure leading in turn to massive water accumulation that can affect vision. Under these conditions, it has been hypothesized that RPE is likely to be exposed to hyperosmolar stress at its apical side. This review summarizes the origins and consequences of osmotic stress in the RPE. Ongoing and further research advances will clarify the mechanisms, at the molecular level, involved in the response of the RPE to osmotic stress and delineate potential novel therapeutic targets and tools. PMID:24910616

  2. Overview of plant pigments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chlorophylls, carotenoids, flavonoids and betalains are four major classes of biological pigments produced in plants. Chlorophylls are the primary pigments responsible for plant green and photosynthesis. The other three are accessary pigments and secondary metabolites that yield non-green colors and...

  3. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  4. Clinical Risk Factors for Poor Anatomic Response to Ranibizumab in Neovascular Age-Related Macular Degeneration§

    PubMed Central

    Guber, Josef; Josifova, Tatjana; Henrich, Paul Bernhard; Guber, Ivo

    2014-01-01

    Purpose: To identify OCT-based anatomical features and clinical characteristics for poor central retinal thickness (CRT) response to ranibizumab in neovascular age-related macular degeneration (AMD). Patients and Methods: Investigating our electronic patient records (Eyeswide), patients with neovascular AMD treated with intravitreal injections of 0.5mg/0.05ml ranibizumab were identified and their notes reviewed. Data collected included gender, age, initial best-corrected visual acuity (BCVA), prior photodynamic therapy, lesion type (classic versus occult), type of macular edema (intraretinal fluid, subretinal fluid, pigment epithelium detachment) and the total number of previous ranibizumab injections. Results: A total of 210 eyes of 182 patients with neovascular AMD were identified. Mean follow-up time was 1.34 years (SD ± 0.77). Central retinal thickness reduction in women was significantly inferior to that in men (p=0.05). Patients with cystoid type macular edema had significantly greater reduction in CRT compared to patients with subretinal fluid (p<0.001) or pigment epithelium detachment (p<0.001). The percentage drop of CRT was no longer statistically significant after the sixth injection. Age, initial BCVA, prior photodynamic therapy and lesion type had no statistically effect on CRT response. Conclusion: Risk factors for poor central retinal thickness response to ranibizumab include female gender and patients with predominant subretinal fluid or pigment epithelium detachment. Furthermore, the anatomical response decreased after the sixth injection of ranibizumab. PMID:24949110

  5. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients.

  6. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration.

    PubMed

    Radu, Roxana A; Mata, Nathan L; Nusinowitz, Steven; Liu, Xinran; Sieving, Paul A; Travis, Gabriel H

    2003-04-15

    Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's disease is accumulation of toxic lipofuscin pigments such as N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment epithelium. This accumulation appears to be responsible for the photoreceptor death and severe visual loss in Stargardt's patients. Here, we tested a therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the synthesis of 11-cis-retinaldehyde and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase in the visual cycle. Light activation of rhodopsin results in its release of all-trans-retinaldehyde, which constitutes the first reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin on lipofuscin accumulation in abcr(-/-) knockout mice. Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy. We observed no significant visual loss in treated abcr(-/-) mice by electroretinography. Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in wild-type mice. These results corroborate the proposed mechanism of A2E biogenesis. Further, they suggest that treatment with isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's patients. Finally, the results suggest that isotretinoin may be an effective treatment for other forms of retinal or macular degeneration associated with lipofuscin accumulation.

  7. Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

    PubMed

    Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P; Vercauteren, Joseph; Brabet, Philippe

    2016-09-01

    Among retinal macular diseases, the juvenile recessive Stargardt disease and the age-related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all-trans-retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti-COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL-induced cell death and reduces hydrogen peroxide (H2 O2 )-induced damage in RPE in a dose-dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases.

  8. Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

    PubMed

    Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P; Vercauteren, Joseph; Brabet, Philippe

    2016-09-01

    Among retinal macular diseases, the juvenile recessive Stargardt disease and the age-related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all-trans-retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti-COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL-induced cell death and reduces hydrogen peroxide (H2 O2 )-induced damage in RPE in a dose-dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases. PMID:27072643

  9. Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible Light-Induced Retinal Degeneration Model in Pigmented Rabbits.

    PubMed

    Wang, Yong; Zhao, Liang; Lu, Feng; Yang, Xue; Deng, Qianchun; Ji, Baoping; Huang, Fenghong

    2015-12-14

    Excessive visible light exposure can induce damage to retinal cells and contribute to the development or progression of age-related macular degeneration. In this study we created a model of phototoxicity in pigmented rabbits. Furthermore, we investigated the protective effect of bilberry anthocyanin extract (BAE, Table A1) and explored the possible mechanisms of action in this model. The model of light-induced retinal damage was established by the pigmented rabbits exposed to light at 18,000 lx for 2 h, and they were sacrificed on day 7. After administration of BAE at dosages of 250 and 500 mg/kg/day, retinal dysfunction was significantly inhibited in terms of electroretinograms, and the decreased thicknesses of retinal outer nuclear layer and lengths of the outer segments of the photoreceptor cells were suppressed in rabbits with retinal degeneration. BAE attenuated the changes caused by light to certain apoptotic proteins (Bax, Bcl-2, and caspase-3). The extract increased the levels of superoxide dismutase, glutathione peroxidase, and catalase, as well as the total antioxidant capacity, but decreased the malondialdehyde level in the retinal cells. BAE inhibited the light-induced elevation in the levels of proinflammatory cytokines and angiogenic parameters (IL-1β and VEGF). Results showed that visible light-induced retinal degeneration model in pigmented rabbits was successfully established and BAE exhibited protective effects by increasing the antioxidant defense mechanisms, suppressing lipid peroxidation and proinflammatory cytokines, and inhibiting retinal cells apoptosis.

  10. A primer on pigmentation.

    PubMed

    Greenhalgh, David G

    2015-01-01

    There is at least a temporary loss of skin pigmentation with all but first-degree burns. Commonly, pigment changes persist for months, and sometimes, permanent changes in skin color add to the ultimate change in appearance that commonly affects burn patients. There are many different treatment modalities for the treatment of pigment changes, but most of them have little scientific basis and often lead to disappointing results. The purpose of this review is to discuss the molecular and cellular mechanisms of skin pigmentation, mechanisms of repigmentation after burns, treatment options for dealing with pigmentation changes, and advice for dealing with the sun after burn injury. PMID:25501768

  11. A primer on pigmentation.

    PubMed

    Greenhalgh, David G

    2015-01-01

    There is at least a temporary loss of skin pigmentation with all but first-degree burns. Commonly, pigment changes persist for months, and sometimes, permanent changes in skin color add to the ultimate change in appearance that commonly affects burn patients. There are many different treatment modalities for the treatment of pigment changes, but most of them have little scientific basis and often lead to disappointing results. The purpose of this review is to discuss the molecular and cellular mechanisms of skin pigmentation, mechanisms of repigmentation after burns, treatment options for dealing with pigmentation changes, and advice for dealing with the sun after burn injury.

  12. Advances in the management of macular degeneration

    PubMed Central

    2014-01-01

    Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition. PMID:24860651

  13. Analysis of Macular Drusen and Blood Test Results in 945 Macaca fascicularis

    PubMed Central

    Nishiguchi, Koji M.; Yokoyama, Yu; Fujii, Yusuke; Fujita, Kosuke; Tomiyama, Yusuke; Kawasaki, Ryo; Furukawa, Toshinori; Ono, Fumiko; Shimozawa, Nobuhiro; Togo, Mutsumi; Suzuki, Michihiro; Nakazawa, Toru

    2016-01-01

    Age-dependent formation of macular drusen caused by the focal accumulation of extracellular deposits beneath the retinal pigment epithelium precede the development of age-related macular degeneration (AMD), one of the leading causes of blindness worldwide. It is established that inflammation contributes to the pathogenesis of drusen and AMD. However, development of a preemptive therapeutic strategy targeting macular drusen and AMD has been impeded by the lack of relevant animal models because most laboratory animals lack macula, an anatomic feature present only in humans and a subset of monkeys. Reportedly, macular drusen and macular degeneration develop in monkeys in an age-dependent manner. In this study, we analyzed blood test results from 945 Macaca fascicularis, 317 with and 628 without drusen. First, a trend test for drusen frequency (the Cochran–Armitage test) was applied to the quartile data for each parameter. We selected variables with an increasing or decreasing trend with higher quartiles at P < 0.05, to which multivariate logistic regression analysis was applied. This revealed a positive association of age (odds ratio [OR]: 1.10 per year, 95% confidence interval [CI]: 1.07–1.12) and white blood cell count (OR: 1.01 per 1 × 103/μl, 95% CI: 1.00–1.01) with drusen. When the monkeys were divided by age, the association between drusen and white blood cell count was only evident in younger monkeys (OR: 1.01 per 1 × 103/μl, 95% CI: 1.00–1.02). In conclusion, age and white blood cell count may be associated with drusen development in M. fascicularis. Systemic inflammation may contribute to drusen formation in monkeys. PMID:27776188

  14. [Transmission electronic microscopy of the inner limiting membrane and epiretinal tissue in idiopathic macular hole].

    PubMed

    Synek, S; Pác, L

    2005-03-01

    The authors examined samples of epimacular tissue obtained during the surgeries of the idiopathic macular hole in different stages of the disease by means of transmission electronic microscopy. In the early stages of the disease only the inner limiting membrane with isolated cells on the vitreous side was present, in later ones of the disease the connective tissue membrane was attached. In rare cases of the later stages of the disease they found the presence of the retinal pigment epithelium (RPE). They suppose the RPE plays an important role in the regeneration of the defects of the retina.

  15. Diode laser photocoagulation for diabetic macular oedema.

    PubMed Central

    Ulbig, M W; McHugh, D A; Hamilton, A M

    1995-01-01

    AIMS--This study aimed to investigate whether diode laser irradiation, which is poorly absorbed by haemoglobin, can induce closure of leaking retinal microvascular lesions in the treatment of diabetic macular oedema. METHODS--Thirty three eyes with clinically significant diabetic macular oedema were treated with a diode laser. Fundus evaluation before and after treatment included visual acuity, stereoscopic biomicroscopy, colour photographs, and fluorescein angiography. RESULTS--At a mean period of review of 6 months macular oedema had completely or partially resolved in 27 eyes. Visual acuity improved in three, deteriorated in one, and was unchanged in 29 eyes. CONCLUSION--Preliminary data suggest that diode laser therapy induces closure of leaking retinal microaneurysms and is effective in the treatment of diabetic macular oedema. Images PMID:7742274

  16. Traumatic macular hole from intentional basketball overinflation.

    PubMed

    Yonekawa, Yoshihiro; Miller, John B; Turalba, Angela V; Eliott, Dean

    2013-01-01

    We report a new mechanism of ocular trauma. A basketball was intentionally overinflated until it exploded, resulting in corneal edema, hyphema, iritis, vitreous hemorrhage, commotio retinae, and a macular hole. The macular hole did not close after observation and subsequent pars plana vitrectomy with posterior hyaloid removal, but a repeat vitrectomy with internal limiting membrane peeling resulted in hole closure. Basketball overinflation to the point of explosion is a potentially blinding practice of which the public and manufacturers should be made aware.

  17. The influence of abdominal pigmentation on desiccation and ultraviolet resistance in two species of Drosophila.

    PubMed

    Matute, Daniel R; Harris, Alexandra

    2013-08-01

    Drosophila yakuba and D. santomea are sister species that differ in their levels of abdominal pigmentation; D. yakuba shows heavily pigmented posterior abdominal segments in both sexes, whereas D. santomea lacks dark pigment anywhere on its body. Using naturally collected lines, we demonstrate the existence of altitudinal variation in abdominal pigmentation in D. yakuba but not in D. santomea. We use the variation in pigmentation within D. yakuba and two body-color mutants in D. yakuba to elucidate selective advantage of differences in pigmentation. Our results indicate that although differences in abdominal pigmentation have no effect on desiccation resistance, lighter pigmentation confers ultraviolet radiation resistance in this pair of species.

  18. Analysis of candidate genes for macular telangiectasia type 2

    PubMed Central

    Parmalee, Nancy L.; Schubert, Carl; Merriam, Joanna E.; Allikmets, Kaija; Bird, Alan C.; Gillies, Mark C.; Peto, Tunde; Figueroa, Maria; Friedlander, Martin; Fruttiger, Marcus; Greenwood, John; Moss, Stephen E.; Smith, Lois E.H.; Toomes, Carmel; Inglehearn, Chris F.

    2010-01-01

    Purpose To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach. Methods Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes. Identified nonsynonymous variants were analyzed to determine whether they co-segregate with the disease in families. Allele frequencies were determined by TaqMan analysis of the large MacTel and control cohorts. Results We identified 23 nonsynonymous variants in 27 candidate genes in at least one proband. Of these, eight were known single nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants were excluded from further analyses. Three previously unidentified missense variants, three missense variants with reported disease association, and five rare variants were analyzed for segregation and/or allele frequencies. No variant fulfilled the criteria of being causal for MacTel. A missense mutation, p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a disease-causing variant in familial exudative vitreoretinopathy, was determined to be a rare benign polymorphism. Conclusions We have ruled out the exons and flanking intronic regions in 27 candidate genes as harboring causal mutations for MacTel. PMID:21179236

  19. Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal Cells: Role in Chemokine Receptor Mediated Age-related Macular Degeneration

    PubMed Central

    Nagineni, Chandrasekharam N.; Kommineni, Vijay K.; Ganjbaksh, Nader; Nagineni, Krishnasai K.; Hooks, John J.; Detrick, Barbara

    2015-01-01

    Chemokine reeptor-3 (CCR-3) was shown to be associated with choroidal neovascularization (CNV) in age-related macular degeneration (AMD). AMD is a vision threatening retinal disease that affects the aging population world-wide. Retinal pigment epithelium and choroid in the posterior part of the retina are the key tissues targeted in the pathogenesis of CNV in AMD. We used human retinal pigment epithelial (HRPE) and choroidal fibroblast (HCHF) cells, prepared from aged adult human donor eyes, to evaluate the expression of major CCR-3 ligands, CCL-5, CCL -7, CCL-11,CCL-24 and CCL-26. Microarray analysis of gene expression in HRPE cells treated with inflammatory cytokine mix (ICM= IFN-γ+TNF-α+IL-1β) revealed 75 and 23-fold increase in CCL-5 and CCL-7 respectively, but not CCL-11, CCL-24 and CCL-26. Chemokine secretion studies of the production of CCL5 and CCL7 by HRPE corroborated with the gene expression analysis data. When the HRPE cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent manner. Similar to the gene expression data, the ICM did not enhance HRPE production of CCL-11, CCL-24 and CCL-26. CCL-11 and CCL-26 were increased with IL-4 treatment and this HRPE production was augmented in the presence of TNF-α and IL1β. When HCHF cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent fashion. IL-4 induced low levels of CCL-11 and CCL-26 in HCHF and this production was significantly enhanced by TNF-α. Under these conditions, neither HRPE nor HCHF were demonstrated to produce CCL-24. These data demonstrate that chronic inflammation triggers CCL-5 and CCL-7 release by HRPE and HCHF and the subsequent interactions with CCR3 may participate in pathologic processes in AMD. PMID:26618046

  20. Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

    PubMed

    Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

    2016-01-01

    Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy.

  1. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.

    PubMed

    Schmidt-Erfurth, Ursula; Waldstein, Sebastian M

    2016-01-01

    Neovascular age-related macular degeneration (AMD) has undergone substantial break-throughs in diagnostic as well as therapeutic respect, with optical coherence tomography (OCT) allowing to identify disease morphology in great detail, and intravitreal anti-vascular endothelial growth factor therapy providing unprecedented benefit. However, these two paths have yet not been combined in an optimal way, real-world outcomes are inferior to expectations, and disease management is largely inefficient in the real-world setting. This dilemma can be solved by identification of valid biomarkers relevant for visual function, disease activity and prognosis, which can provide solid guidance for therapeutic management on an individual level as well as on the population base. Qualitative and quantitative morphological features obtained by advanced OCT provide novel insight into exudative and degenerative stages of neovascular AMD. However, conclusions from structure/function correlations evolve differently from previous paradigms. While central retinal thickness was used as biomarker for guiding retreatment management in clinical trials and practice, fluid localization in different compartments offers superior prognostic value: Intraretinal cystoid fluid has a negative impact on visual acuity and is considered as degenerative when persisting through the initial therapeutic interval. Subretinal fluid is associated with superior visual benefit and a lower rate of progression towards geographic atrophy. Detachment of the retinal pigment epithelium was identified as most pathognomonic biomarker, often irresponsive to therapy and responsible for visual decline during a pro-re-nata regimen. Alterations of neurosensory tissue are usually associated with irreversible loss of functional elements and a negative prognosis. Novel OCT technologies offer crucial insight into corresponding changes at the level of the photoreceptor--retinal pigment epithelial--choriocapillary unit, identifying

  2. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.

    PubMed

    Schmidt-Erfurth, Ursula; Waldstein, Sebastian M

    2016-01-01

    Neovascular age-related macular degeneration (AMD) has undergone substantial break-throughs in diagnostic as well as therapeutic respect, with optical coherence tomography (OCT) allowing to identify disease morphology in great detail, and intravitreal anti-vascular endothelial growth factor therapy providing unprecedented benefit. However, these two paths have yet not been combined in an optimal way, real-world outcomes are inferior to expectations, and disease management is largely inefficient in the real-world setting. This dilemma can be solved by identification of valid biomarkers relevant for visual function, disease activity and prognosis, which can provide solid guidance for therapeutic management on an individual level as well as on the population base. Qualitative and quantitative morphological features obtained by advanced OCT provide novel insight into exudative and degenerative stages of neovascular AMD. However, conclusions from structure/function correlations evolve differently from previous paradigms. While central retinal thickness was used as biomarker for guiding retreatment management in clinical trials and practice, fluid localization in different compartments offers superior prognostic value: Intraretinal cystoid fluid has a negative impact on visual acuity and is considered as degenerative when persisting through the initial therapeutic interval. Subretinal fluid is associated with superior visual benefit and a lower rate of progression towards geographic atrophy. Detachment of the retinal pigment epithelium was identified as most pathognomonic biomarker, often irresponsive to therapy and responsible for visual decline during a pro-re-nata regimen. Alterations of neurosensory tissue are usually associated with irreversible loss of functional elements and a negative prognosis. Novel OCT technologies offer crucial insight into corresponding changes at the level of the photoreceptor--retinal pigment epithelial--choriocapillary unit, identifying

  3. Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration.

    PubMed

    Singh, Ruchira; Kuai, David; Guziewicz, Karina E; Meyer, Jackelyn; Wilson, Molly; Lu, Jianfeng; Smith, Molly; Clark, Eric; Verhoeven, Amelia; Aguirre, Gustavo D; Gamm, David M

    2015-11-01

    Degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is essential for vision, and studies have implicated altered POS processing in the pathogenesis of some retinal degenerative diseases. Consistent with this concept, a recently established hiPSC-RPE model of inherited macular degeneration, Best disease (BD), displayed reduced rates of POS breakdown. Herein we utilized this model to determine (i) if disturbances in protein degradation pathways are associated with delayed POS digestion and (ii) whether such defect(s) can be pharmacologically targeted. We found that BD hiPSC-RPE cultures possessed increased protein oxidation, decreased free-ubiquitin levels, and altered rates of exosome secretion, consistent with altered POS processing. Application of valproic acid (VPA) with or without rapamycin increased rates of POS degradation in our model, whereas application of bafilomycin-A1 decreased such rates. Importantly, the negative effect of bafilomycin-A1 could be fully reversed by VPA. The utility of hiPSC-RPE for VPA testing was further evident following examination of its efficacy and metabolism in a complementary canine disease model. Our findings suggest that disturbances in protein degradation pathways contribute to the POS processing defect observed in BD hiPSC-RPE, which can be manipulated pharmacologically. These results have therapeutic implications for BD and perhaps other maculopathies. PMID:26300224

  4. Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration.

    PubMed

    Karan, G; Lillo, C; Yang, Z; Cameron, D J; Locke, K G; Zhao, Y; Thirumalaichary, S; Li, C; Birch, D G; Vollmer-Snarr, H R; Williams, D S; Zhang, K

    2005-03-15

    Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness. PMID:15749821

  5. Regulation of age-related macular degeneration-like pathology by complement factor H

    PubMed Central

    Toomey, Christopher B.; Kelly, Una; Saban, Daniel R.; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/− and Cfh−/− mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/− and Cfh−/− mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/− mice. We demonstrate that such pathology is a function of excess complement activation in Cfh+/− mice versus complement deficiency in Cfh−/− animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

  6. UV-induced retinal proteome changes in the rat model of age-related macular degeneration.

    PubMed

    Kraljević Pavelić, Sandra; Klobučar, Marko; Sedić, Mirela; Micek, Vedran; Gehrig, Peter; Grossman, Jonas; Pavelić, Krešimir; Vojniković, Božidar

    2015-09-01

    Age-related macular degeneration (AMD) is characterized by irreversible damage of photoreceptors in the central posterior part of the retina, called the macula and is the most common cause of vision loss in those aged over 50. A growing body of evidence shows that cumulative long-term exposure to UV radiation may be harmful to the retina and possibly leads to AMD irrespective of age. In spite of many research efforts, cellular and molecular mechanisms leading to UV-induced retinal damage and possibly retinal diseases such as AMD are not completely understood. In the present study we explored damage mechanisms accounting for UV-induced retinal phototoxicity in the rats exposed to UVA and UVB irradiation using a proteomics approach. Our study showed that UV irradiation induces profound changes in the retinal proteomes of the rats associated with the disruption of energy homeostasis, oxidative stress, DNA damage response and structural and functional impairments of the interphotoreceptor matrix components and their cell surface receptors such as galectins. Two small leucine-rich proteoglycans, biglycan and lumican, were identified as phototoxicity biomarkers associated with UV-induced disruption of interphotoreceptor matrix (IPM). In addition, UVB induced activation of Src kinase, which could account for cytoskeletal rearrangements in the retina was observed at the proteomics level. Pharmacological intervention either to target Src kinase with the aim of preventing cytoskeletal rearrangements in the retinal pigment epithelium (RPE) and neuronal retina or to help rebuild damaged IPM may provide fresh avenues of treatment for patients suffering from AMD. PMID:26071645

  7. Digital image processing-an alternate tool for monitoring of pigment levels in cultured cells with special reference to green alga Haematococcus pluvialis.

    PubMed

    Kamath, Sandesh B; Chidambar, Shalini; Brinda, B R; Kumar, M A; Sarada, R; Ravishankar, G A

    2005-11-15

    A method for analyzing carotenoid content in Haematococcus pluvialis, a green alga was developed using digital image processing (DIP) and an artificial neural network (ANN) model. About 90 images of algal cells in various phases of growth were processed with the tools of DIP. A good correlation of R(2)=0.967 was observed between carotenoid content as estimated by analytical method and DIP. Similar correlation was also observed in case of chlorophyll. Since the conventional methods of carotenoid estimation are time consuming and result in loss of pigments during analysis, DIP method was found to be an effective online monitoring method. This method will be useful in measurement of pigments in cultured cells.

  8. Macular Hole Formation After Intravitreal Ranibizumab Injection in Wet Age-Related Macular Degeneration

    PubMed Central

    Mukherjee, Chandoshi; Mitra, Arijit; Kumar, N. Ajith; Elsherbiny, Samer; Lip, Peck Lin

    2015-01-01

    Ranibizumab is a monoclonal antibody fragment that inhibits angiogenesis by inhibiting vascular endothelial growth factor A, used as a treatment for patients with wet aged-related macular degeneration (ARMD). Adverse effects from intravitreal Ranibizumab injections are well recognised. Macular hole formation following Ranibizumab injection is a complication that has been recently reported in few case reports. We present a larger case series of five patients, who developed full thickness macular holes (FTMH) after intravitreal Ranibizumab injections for treatment of wet ARMD that we were aware of between 2009 and 2013. PMID:26962382

  9. Acute serous macular detachment and cystoid macular edema after uncomplicated phacoemulsification using standard dose subconjunctival cefuroxime.

    PubMed

    Kontos, Andreas; Mitry, Danny; Althauser, Susanne; Jain, Saurabh

    2014-09-01

    Acute toxic serous macular detachment after cataract surgery is very rare, and has been described previously with the use of high concentrations of intra-cameral cefuroxime. We report a case of serous macular detachment and cystoid macular edema 1 day after uncomplicated phacoemulsification using standard dose subconjunctival cefuroxime at the end of surgery. Our case demonstrates that subconjunctival cefuroxime may cause retinal toxicity in a similar fashion to intra-cameral cefuroxime, possibly due to entry of the drug into the anterior chamber through the section or trans-scleral absorption. To our knowledge, this is the first report of this complication with subconjunctival administration of cefuroxime.

  10. Squalamine lactate for exudative age-related macular degeneration.

    PubMed

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies. PMID:16935213

  11. Ion transport in pigmentation

    PubMed Central

    Bellono, Nicholas W.; Oancea, Elena V.

    2014-01-01

    Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in mammals. Defects in the complex mechanisms involved in melanin synthesis and regulation result in vision and pigmentation deficits, impaired development of the visual system,, and increased susceptibility to skin and eye cancers. Ion transport across cellular membranes is critical for many biological processes, including pigmentation, but the molecular mechanisms by which it regulates melanin synthesis, storage, and transfer are not understood. In this review we first discuss ion channels and transporters that function at the plasma membrane of melanocytes; in the second part we consider ion transport across the membrane of intracellular organelles, with emphasis on melanosomes. We discuss recently characterized lysosomal and endosomal ion channels and transporters associated with pigmentation phenotypes. We then review the evidence for melanosomal channels and transporters critical for pigmentation, discussing potential molecular mechanisms mediating their function. The studies investigating ion transport in pigmentation physiology open new avenues for future research and could reveal novel molecular mechanisms underlying melanogenesis. PMID:25034214

  12. Ion transport in pigmentation.

    PubMed

    Bellono, Nicholas W; Oancea, Elena V

    2014-12-01

    Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in mammals. Defects in the complex mechanisms involved in melanin synthesis and regulation result in vision and pigmentation deficits, impaired development of the visual system, and increased susceptibility to skin and eye cancers. Ion transport across cellular membranes is critical for many biological processes, including pigmentation, but the molecular mechanisms by which it regulates melanin synthesis, storage, and transfer are not understood. In this review we first discuss ion channels and transporters that function at the plasma membrane of melanocytes; in the second part we consider ion transport across the membrane of intracellular organelles, with emphasis on melanosomes. We discuss recently characterized lysosomal and endosomal ion channels and transporters associated with pigmentation phenotypes. We then review the evidence for melanosomal channels and transporters critical for pigmentation, discussing potential molecular mechanisms mediating their function. The studies investigating ion transport in pigmentation physiology open new avenues for future research and could reveal novel molecular mechanisms underlying melanogenesis.

  13. Protective responses to sublytic complement in the retinal pigment epithelium.

    PubMed

    Tan, Li Xuan; Toops, Kimberly A; Lakkaraju, Aparna

    2016-08-01

    The retinal pigment epithelium (RPE) is a key site of injury in inherited and age-related macular degenerations. Abnormal activation of the complement system is a feature of these blinding diseases, yet how the RPE combats complement attack is poorly understood. The complement cascade terminates in the cell-surface assembly of membrane attack complexes (MACs), which promote inflammation by causing aberrant signal transduction. Here, we investigated mechanisms crucial for limiting MAC assembly and preserving cellular integrity in the RPE and asked how these are compromised in models of macular degeneration. Using polarized primary RPE and the pigmented Abca4(-/-) Stargardt disease mouse model, we provide evidence for two protective responses occurring within minutes of complement attack, which are essential for maintaining mitochondrial health in the RPE. First, accelerated recycling of the membrane-bound complement regulator CD59 to the RPE cell surface inhibits MAC formation. Second, fusion of lysosomes with the RPE plasma membrane immediately after complement attack limits sustained elevations in intracellular calcium and prevents mitochondrial injury. Cholesterol accumulation in the RPE, induced by vitamin A dimers or oxidized LDL, inhibits these defense mechanisms by activating acid sphingomyelinase (ASMase), which increases tubulin acetylation and derails organelle traffic. Defective CD59 recycling and lysosome exocytosis after complement attack lead to mitochondrial fragmentation and oxidative stress in the RPE. Drugs that stimulate cholesterol efflux or inhibit ASMase restore both these critical safeguards in the RPE and avert complement-induced mitochondrial injury in vitro and in Abca4(-/-) mice, indicating that they could be effective therapeutic approaches for macular degenerations. PMID:27432952

  14. Intraoperative electrophysiological evaluations of macular function during peripheral scleral indentation

    PubMed Central

    Akiyama, Goichi; Matsumoto, Celso Soiti; Shinoda, Kei; Terauchi, Gaku; Matsumoto, Harue; Watanabe, Emiko; Iwata, Takeshi; Mizota, Atsushi; Miyake, Yozo

    2016-01-01

    Scleral indentation is widely used to examine the peripheral fundus, however it can increase the intraocular pressure (IOP) to high levels which can then affect retinal function. We evaluated the effects of scleral indentation on the macular function electrophysiologically. Intraoperative focal macular electroretinograms (iFMERGs) were recorded with and without controlling the IOP in 7 eyes. Without IOP control, the IOP increased from 21.7 ± 4.9 to 92.7 ± 20.2 mmHg significantly (P = 0.020) and the amplitudes of the b-wave (from 6.29 ± 1.160 to 3.71 ± 1.98 uV, P = 0.007), on-photopic negative response (from 2.29 ± 0.99 to 0.72 ± 0.47 uV, on-PhNR, P = 0.005), and d-wave (from 2.57 ± 0.41 to 1.64 ± 0.69 uV, P = 0.007) decreased significantly soon after beginning the indentation. All values returned to the baseline levels after releasing the indentation. In the eyes with IOP controlled, the IOP and the amplitude of all components did not change significantly during and after the indentation except the on-PhNR amplitude which was significantly reduced during the indentation. The changes in the iFMERGs and macular function caused by scleral indentation were transient and reversible. The changes can be minimized by controlling the IOP. PMID:27762313

  15. Simulating vision with and without macular disease.

    PubMed

    Marmor, David J; Marmor, Michael F

    2010-01-01

    Conventional photographs do not show how, at any moment of visual fixation, neural vision is clear only in the foveal center. We have developed new computer simulations to show both normal vision and vision with macular disease. These simulations show the nature of momentary vision for life tasks such as reading, facial recognition, and walking in the street. They also dramatically show the impact of macular disease (with scotomas and visual distortion), as there is no surrounding region of clarity. We hope these images will be instructive to both physicians and patients.

  16. Macular thickness measured by stratus optical coherence tomography in patients with diabetes type 2 and mild nonproliferative retinopathy without clinical evidence of macular edema.

    PubMed

    Pires, Isabel; Santos, Ana Rita; Nunes, Sandrina; Lobo, Conceição

    2013-01-01

    To evaluate macular thickness in eyes with mild nonproliferative diabetic retinopathy (NPDR), patients with diabetes type 2, NPDR level 20 or 35, and without evidence of clinical macular edema underwent best-corrected visual acuity assessment, color fundus photography and Stratus optical coherence tomography. Mean center point thickness (CPT) and mean central subfield (CSF) thickness were compared with those of a healthy control population. 410 eyes/patients aged 61.2 ± 8.3 years, and with glycosylated hemoglobin of 7.9 ± 1.5% were included. Mean CPT and CSF were 186.6 ± 28.4 and 215.2 ± 25 µm, respectively, significantly increased compared to healthy subjects (p < 0.001). CSF thickness was abnormally increased in 17.6% of the patients, with values within the normal range in 79.5%, and abnormally decreased in 2.9%. CPT and CSF thickness were significantly thicker in men. No systemic factors showed a significant association. A significant increase in the macular thickness was found in eyes/patients with mild NPDR without clinical macular edema; however, only 17.6% of the eyes/patients had abnormally increased values and less than 3% abnormally decreased values.

  17. Dynamics of the Macular Hole-Silicone Oil Tamponade Interface with Patient Positioning as Imaged by Spectral Domain Optical Coherence Tomography

    PubMed Central

    Oster, Stephen F.; Mojana, Francesca; Bartsch, Dirk-Uwe G.; Goldbaum, Michael; Freeman, William R.

    2010-01-01

    Purpose To evaluate with spectral domain optical coherence tomography (SD-OCT) the relationship between the retina and overlying silicone oil tamponade after macular hole surgery, and to evaluate how this relationship changes with patient positioning. Patients and Methods Retrospective consecutive case series of 10 eyes from 9 patients who underwent macular hole surgery with silicone oil tamponade and subsequent SD-OCT scans. Four of the included eyes were also imaged with patients in face-down posture to determine if the silicone-retina apposition changes with prone positioning. Finally, a single patient was additionally scanned in the lateral and supine positions. Results The posterior surface of the silicone oil bubble was well visualized in all 10 eyes. In the majority of eyes (7/10) the oil tamponade bridged across the macular hole creating a pre-foveal fluid space, but in 3 eyes the silicone oil filled the macular hole and was seen in touch with the underlying foveal depression or retinal pigment epithelium. In 75% of eyes (3/4) the silicone oil-retinal approximation did not vary with face-down position. Supine positioning clearly floated the silicone tamponade anteriorly and off of the retinal surface. Conclusions Silicone oil tamponade can either bridge across macular holes, or in a novel finding, can fill the underlying foveal depression or macular hole space. Generally, the oil position is stable between face-forward and prone SD-OCT images, suggesting that either of these patient positions allows waterproofing of the underlying macular hole. Finally, our images confirm that supine positioning should be avoided post-operatively as it leads to loss of oil-retinal tamponade. PMID:20531144

  18. Current therapeutic developments in atrophic age-related macular degeneration.

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age-Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  19. Current Therapeutic Development for Atrophic Age-related Macular Degeneration

    PubMed Central

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  20. Pigment-protein complexes

    SciTech Connect

    Siegelman, H W

    1980-01-01

    The photosynthetically-active pigment protein complexes of procaryotes and eucaryotes include chlorophyll proteins, carotenochlorophyll proteins, and biliproteins. They are either integral components or attached to photosynthetic membranes. Detergents are frequently required to solubilize the pigment-protein complexes. The membrane localization and detergent solubilization strongly suggest that the pigment-protein complexes are bound to the membranes by hydrophobic interactions. Hydrophobic interactions of proteins are characterized by an increase in entropy. Their bonding energy is directly related to temperature and ionic strength. Hydrophobic-interaction chromatography, a relatively new separation procedure, can furnish an important method for the purification of pigment-protein complexes. Phycobilisome purification and properties provide an example of the need to maintain hydrophobic interactions to preserve structure and function.

  1. Assessment of Macular Function during Vitrectomy: New Approach Using Intraoperative Focal Macular Electroretinograms

    PubMed Central

    Matsumoto, Celso Soiti; Shinoda, Kei; Terauchi, Gaku; Matsumoto, Harue; Mizota, Atsushi; Miyake, Yozo

    2015-01-01

    Purpose To describe a new technique to record focal macular electroretinograms (FMERGs) during vitrectomy to assess macular function. Methods Intraoperative FMERGs (iFMERGs) were recorded in ten patients (10 eyes) who undergo vitrectomy. iFMERGs were elicited by focal macular stimulation. The stimulus light was directed to the macular area through a 25 gauge (25G) glass fiber optic bundle. Background light was delivered through a dual chandelier-type light fiber probe. Focal macular responses elicited with combinations of stimulus and background luminances were analyzed. Results A stimulus luminance that was approximately 1.75 log units brighter than the background light was able to elicit focal macular responses that were not contaminated by stray light responses. Thus, a stimulus luminance of 160 cd/m2 delivered on a background of 3 cd/m2 elicited iFMEGs from only the stimulated area. This combination of stimulus and background luminances did not elicit a response when the stimulus was projected onto the optic nerve head. The iFMERGs elicited by a 10° stimulus with a duration of 100 ms and an interstimulus interval of 150 ms consisted of an a-, b-, and d-waves, the oscillatory potentials, and the photopic negative response (PhNR). Conclusions Focal ERGs with all components can be recorded from the macula and other retinal areas during vitreous surgery. This new technique will allow surgeons to assess the function of focal areas of the retina intraoperatively. PMID:26658489

  2. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  3. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  4. Management of traumatic macular holes: case report.

    PubMed

    Brasil, Oswaldo Ferreira Moura; Brasil, Oswaldo Moura

    2008-01-01

    Traumatic macular hole is a disease whose pathogenesis is not fully understood and the best treatment guideline is controversial. We report 2 cases of traumatic macular hole with different treatment approaches. In the first case, a 9-year-old boy presented with a traumatic macular hole secondary to blunt ocular trauma with a stone, and initial vision of 20/300. He underwent surgical repair and his final vision was 20/70 with hole closure after a 1 year follow-up. In the second case, a 20-year-old woman suffered a penetrating bullet wound on the left side of her forehead. The injury caused optic nerve head avulsion in the left eye with loss of light perception. The right eye had a traumatic macular hole and signs suggestive of sclopetaria chorioretinitis, with 20/60 vision. This case was initially observed and vision improved to 20/30 with reduction of the hole diameter. Vision and hole diameter remained stable after 8 months.

  5. Macular Amyloidosis and Epstein-Barr Virus

    PubMed Central

    Nahidi, Yalda; Tayyebi Meibodi, Naser; Meshkat, Zahra; Nazeri, Narges

    2016-01-01

    Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV) DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group). There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8%) and control (23.8%) groups (P = 0.08). Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis. PMID:26981113

  6. Cental Macular Thickness in Patients with Type 2 Diabetes Mellitus without Clinical Retinopathy.

    PubMed

    Demir, Mehmet; Dirim, Burcu; Acar, Zeynep; Yılmaz, Murat; Sendul, Yekta

    2013-01-01

    Objective. To compare central macular thickness (CMT) of diabetic patients with type 2 diabetes without clinical retinopathy and healthy subjects. Materials and Methods. Optical coherence tomography (OCT) measurements were performed in 124 eyes of 62 subjects with diabetes mellitus without clinical retinopathy (study group: 39 females, 23 males; mean age: 55.06 ± 9.77 years) and in 120 eyes of 60 healthy subjects (control group: 35 females, 25 males; mean age: 55.78 ± 10.34 years). Blood biochemistry parameters were analyzed in all cases. The data for central macular thickness (at 1 mm), the levels of fasting plasma glucose, and glycosylated hemoglobin (HbA1c) were compared in both groups. Results. The mean central macular thickness was 232.12 ± 24.41 µm in the study group and 227.19 ± 29.94 µm in the control group. The mean HbA1c level was 8.92 ± 2.58% in the study group and 5.07 ± 0.70% in the control group (P = 0.001). No statistically significant relationship was found between CMT, HbA1c, and fasting plasma glucose level in either group (P > 0.05). Conclusions. Central macular thickness was not significantly thicker in patients with type 2 diabetes without clinical retinopathy than in healthy subjects. PMID:23691279

  7. Ocular Risk Factors for Age-related Macular Degeneration: The Los Angeles Latino Eye Study (LALES)

    PubMed Central

    Fraser-Bell, Samantha; Choudhury, Farzana; Klein, Ronald; Azen, Stanley; Varma, Rohit

    2010-01-01

    Purpose To assess the association of ocular factors and age-related macular degeneration (AMD) in Latinos. Design Population-based, cross-sectional study of 6357 self-identified Latinos aged 40 years and older. Methods Ophthalmic examination included subjective refraction, measurement of axial length, evaluation of iris color, Lens Opacities Classification System II (LOCS II) grading of cataracts, and stereoscopic macular photographs for AMD lesions. Generalized estimating equation analysis incorporated data from both eyes to estimate odds ratios adjusted for covariates. Results After controlling for confounders (age, gender and smoking), prior cataract surgery was associated with advanced AMD (OR: 2.8, 95% CI 1.0, 7.8), increased retinal pigment (OR: 1.6, 95% CI 1.0, 1.5) and retinal pigment epithelial depigmentation (OR: 2.2, 95% CI 1.1, 4.4). The presence of any lens opacity was associated with soft drusen (OR: 1.2; 95% CI 1.0, 1.5). Longer axial length (per mm) was associated with a decreased odds of soft drusen, increased retinal pigment, and geographic atrophy (GA) (ORs: 0.8 [95% CI 0.7, 0.9], 0.8 [95% CI 0.7, 0.9], 0.7 [95% CI 0.5, 0.9], respectively. Myopia was inversely associated with soft drusen (OR: 0.8; 95% CI 0.7, 1.0). Lighter colored irises were associated with GA (OR: 5.0; 95% CI 1.0, 25.3). Conclusions Cross-sectional associations of ocular factors such as cataract, cataract surgery, and refractive errors with early AMD lesions found in Latinos were consistent with those in whites. Additionally, prior cataract surgery was associated with advanced AMD. PMID:20138605

  8. Isotretinoin treatment inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration.

    PubMed

    Radu, Roxana A; Mata, Nathan L; Nusinowitz, Steven; Liu, Xinran; Travis, Gabriel H

    2004-01-01

    Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's discase is accumulation of toxic lipofuscin pigments such as N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment epithelium (RPE). This accumulation appears to be responsible for the photoreceptor death and severe visual loss in Stargardt's patients. Here, we tested a novel therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the synthesis of 11-cis-retinaldehyde (11cRAL) and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase (11cRDH) in the visual cycle. Light activation of rhodopsin results in its release of all-trans-retinaldehyde (atRAL), which constitutes the first reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin on lipofuscin accumulation in abcr-/- knockout mice. Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy. We observed no significant visual loss in treated abcr-/- mice by electroretinography. Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in wild-type mice. These results corroborate the proposed mechanism of A2E biogenesis. Further, they suggest that treatment with isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's patients. Finally, the results suggest that isotretinoin may be an effective treatment for other forms of retinal or macular degeneration associated with lipofuscin accumulation.

  9. Confirmation of linkage of Best`s macular dystrophy to 11q13, and evidence for genetic heterogeneity

    SciTech Connect

    Mansergh, F.C.; Kenna, P.F.; Farrar, G.J.

    1994-09-01

    Best`s macular dystrophy, also known as vitelliform macular degeneration, is an autosomal dominant, early onset form of macular degeneration. The disease is characterized by a roughly circular deposit of lipofuscin beneath the pigment epithelium of the retinal macula. Linkage studies were performed in two families, one Irish and one German, segregating typical Best`s macular dystrophy. In the Irish family (BTMD1), linkage analysis mapped the disease causing gene to chromosome 11q13, in a 10 cM region between the microsatellite markers PYGM and D11S871. Both markers showed different recombinants with the disease phenotype. This is a region that has previously shown linkage in families affected with Best`s macular dystrophy. Lod scores of 9.63, 9.12, 6.92, and 6.83 at zero recombination, were obtained with markers D11S1344, D11S1361, D11S1357 and D11S903, respectively. This data places the disease locus definitvely within the region between PYGM and D11S871. Linkage has been significantly excluded in this region in the German family (FamE), thereby providing evidence for genetic heterogeneity in this disease. The retinal specific gene, rod outer membrane protein 1 (ROM1), which maps to this region, has been screened for mutations in family BTMD1 by SSCPE analysis and by direct sequencing. Some of the promoter region, the three exons, and both introns have been sequenced; however, no mutations were found. It is likely that a gene other than ROM1 within this region may be responsible for causing the disease phenotype.

  10. The Intravitreal Autologous Platelet Concentrate Injection as an Adjunct of Vitrectomy for the Treatment of Refractory Macular Holes

    ClinicalTrials.gov

    2014-03-06

    Macular Hole With High Myopia (Spherical Equivalent ≤ -6.0 Diopters) or,; Large Size Macular Hole (Diameter > 600 Microns) or; Recurred or Failed Macular Hole From Previous Surgery; or Chronic Macular Hole (Symptom Duration > 6 Months)

  11. A2E and lipofuscin distributions in macaque retinal pigment epithelium are similar to human.

    PubMed

    Pallitto, Patrick; Ablonczy, Zsolt; Jones, E Ellen; Drake, Richard R; Koutalos, Yiannis; Crouch, Rosalie K; Donello, John; Herrmann, Julia

    2015-10-01

    The accumulation of lipofuscin, an autofluorescent aging marker, in the retinal pigment epithelium (RPE) has been implicated in the development of age-related macular degeneration (AMD). Lipofuscin contains several visual cycle byproducts, most notably the bisretinoid N-retinylidene-N-retinylethanolamine (A2E). Previous studies with human donor eyes have shown a significant mismatch between lipofuscin autofluorescence (AF) and A2E distributions. The goal of the current project was to examine this relationship in a primate model with a retinal anatomy similar to that of humans. Ophthalmologically naive young (<10 years., N = 3) and old (>10 years., N = 4) Macaca fascicularis (macaque) eyes, were enucleated, dissected to yield RPE/choroid tissue, and flat-mounted on indium-tin-oxide-coated conductive slides. To compare the spatial distributions of lipofuscin and A2E, fluorescence and mass spectrometric imaging were carried out sequentially on the same samples. The distribution of lipofuscin fluorescence in the primate RPE reflected previously obtained human results, having the highest intensities in a perifoveal ring. Contrarily, A2E levels were consistently highest in the periphery, confirming a lack of correlation between the distributions of lipofuscin and A2E previously described in human donor eyes. We conclude that the mismatch between lipofuscin AF and A2E distributions is related to anatomical features specific to primates, such as the macula, and that this primate model has the potential to fill an important gap in current AMD research. PMID:26223373

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

    SciTech Connect

    Vargis, Elizabeth A.; Peterson, Cristen B.; Morrell-Falvey, Jennifer L.; Retterer, Scott T.; Collier, Charles Patrick

    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 that 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.

  13. 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.; Retterer, Scott T.; Collier, Charles Patrick

    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

  14. Pathological consequences of long-term mitochondrial oxidative stress in the mouse retinal pigment epithelium.

    PubMed

    Seo, Soo-jung; Krebs, Mark P; Mao, Haoyu; Jones, Kyle; Conners, Mandy; Lewin, Alfred S

    2012-08-01

    Oxidative stress in the retinal pigment epithelium (RPE) is hypothesized to be a major contributor to the development of age-related macular degeneration (AMD). Mitochondrial manganese superoxide dismutase (MnSOD) is a critical antioxidant protein that scavenges the highly reactive superoxide radical. We speculated that specific reduction of MnSOD in the RPE will increase the level of reactive oxygen species in the retina/RPE/choroid complex leading to pathogenesis similar to geographic atrophy. To test this hypothesis, an Sod2-specific hammerhead ribozyme (Rz), delivered by AAV2/1 and driven by the human VMD2 promoter was injected subretinally into C57BL/6J mice. Dark-adapted full field electroretinogram (ERG) detected a decrease in the response to light. We investigated the age-dependent phenotypic and morphological changes of the outer retina using digital fundus imaging and SD-OCT measurement of ONL thickness. Fundus microscopy revealed pigmentary abnormalities in the retina and these corresponded to sub-retinal and sub-RPE deposits seen in SD-OCT B-scans. Light and electron microscopy documented the localization of apical deposits and thickening of the RPE. In RPE flat-mounts we observed abnormally displaced nuclei and regions of apparent fibrosis in the central retina of the oldest mice. This region was surrounded by enlarged and irregular RPE cells that have been observed in eyes donated by AMD patients and in other mouse models of AMD.

  15. Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis

    PubMed Central

    Liu, Jian; Copland, David A.; Theodoropoulou, Sofia; Chiu, Hsi An Amy; Barba, Miriam Durazo; Mak, Ka Wang; Mack, Matthias; Nicholson, Lindsay B.; Dick, Andrew D.

    2016-01-01

    Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2+ monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development. PMID:26847702

  16. Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration.

    PubMed

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

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness. PMID:27605007

  17. Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration

    PubMed Central

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

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness. PMID:27605007

  18. Biology of pigmentation

    SciTech Connect

    Parker, F.

    1981-01-01

    The many factors involved in the normal pigmentation of human skin are highly complex involving anatomic, biochemical, and genetic aspects of melanocytes in the skin and the influence of UV light and various hormones on the melanocytes. It is probably more than just coincidence that the melanocytes, which are of neurogenic origin, are so responsive to several trophic hormones produced in the brain. Understanding of the various factors involved in the normal pigmentary process is crucial to explaining the many alterations and anomalies in human pigmentation.

  19. [Effect of prostaglandin synthesis inhibitors of diabetic cystoid macular edema].

    PubMed

    Kieselbach, G; Juen, S

    1990-01-01

    In most cases, diabetic macular edema is treated successfully with central laser photocoagulation. However, only few studies report such favorable results in cystoid macular edema, which has a poor visual prognosis. In the present prospective study on diabetics with cystoid macular edema, aged less than 40 years, a better visual outcome was obtained in patients treated with prostaglandin synthesis inhibitors than in an untreated group. PMID:2345629

  20. Pigments in avocado tissue and oil.

    PubMed

    Ashton, Ofelia B O; Wong, Marie; McGhie, Tony K; Vather, Rosheila; Wang, Yan; Requejo-Jackman, Cecilia; Ramankutty, Padmaja; Woolf, Allan B

    2006-12-27

    Pigments are important contributors to the appearance and healthful properties of both avocado fruits and the oils extracted from these fruits. This study determined carotenoid and chlorophyll pigment concentrations in the skin and three sections of the flesh (outer dark green, middle pale green, and inner yellow flesh-nearest the seed) and anthocyanin concentrations in the skin of Hass avocado during ripening at 20 degrees C. Pigments were extracted from frozen tissue with acetone and measured using high-performance liquid chromatography. Pigments were also measured in the oil extracted from freeze-dried tissue sections by an accelerated solvent extraction system using hexane. Carotenoids and chlorophylls identified in the skin, flesh, and oil were lutein, alpha-carotene, beta-carotene, neoxanthin, violaxanthin, zeaxanthin, antheraxanthin, chlorophylls a and b, and pheophytins a and b with the highest concentrations of all pigments in the skin. Chlorophyllides a and b were identified in the skin and flesh tissues only. As the fruit ripened and softened, the skin changed from green to purple/black, corresponding to changes in skin hue angle, and a concomitant increase in cyanidin 3-O-glucoside and the loss of chlorophyllide a. In flesh tissue, chroma and lightness values decreased with ripening, with no changes in hue angle. The levels of carotenoids and chlorophylls did not change significantly during ripening. As fruit ripened, the total chlorophyll level in the oil from the flesh sections remained constant but declined in the oil extracted from the skin.

  1. Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

    PubMed Central

    Shimada, Yoshiaki; Horiguchi, Masayuki

    2016-01-01

    ABSTRACT Leber hereditary optic neuropathy (LHON) causes visual loss, predominantly in healthy young men. We recently examined a patient who previously had bilateral macular holes and subsequently developed LHON at 74 years of age. Although his central scotomas were initially attributed to the macular holes, his visual acuity declined following an initial improvement after operative closure of the macular holes; thus, other diagnoses, including LHON, were considered. Furthermore, macular optical coherence tomography (OCT) images remained unchanged in this time. A mitochondrial genetic analysis identified a 11778G→A mutation. From this case, we propose that LHON remains in the differential diagnosis even in older patients, as has previously been reported. PMID:27335507

  2. Management of pseudophakic cystoid macular edema.

    PubMed

    Guo, Suqin; Patel, Shriji; Baumrind, Ben; Johnson, Keegan; Levinsohn, Daniel; Marcus, Edward; Tannen, Brad; Roy, Monique; Bhagat, Neelakshi; Zarbin, Marco

    2015-01-01

    Pseudophakic cystoid macular edema (PCME) is a common complication following cataract surgery. Acute PCME may resolve spontaneously, but some patients will develop chronic macular edema that affects vision and is difficult to treat. This disease was described more than 50 years ago, and there are multiple options for clinical management. We discuss mechanisms, clinical efficacy, and adverse effects of these treatment modalities. Topical non-steroidal anti-inflammatory agents and corticosteroids are widely used and, when combined, may have a synergistic effect. Intravitreal corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) agents have shown promise when topical medications either fail or have had limited effects. Randomized clinical studies evaluating anti-VEGF agents are needed to fully evaluate benefits and risks. When PCME is either refractory to medical therapy or is associated with significant vitreous involvement, pars plana vitrectomy has been shown to improve outcomes, though it is associated with additional risks.

  3. [Functional characteristics of macular telangiectasia type 2].

    PubMed

    Heeren, T F C; Krüger, E; Holz, F G; Charbel Issa, P

    2014-09-01

    The first symptoms of macular telangiectasia type 2 usually occur between 50 and 70 years of age. Functional alterations topographically correspond to the morphological changes. Characteristic paracentral scotomata due to focal photoreceptor atrophy can be detected using microperimetry. The predominant paracentral functional loss may cause reading difficulties despite visual acuity in the range between 20/20 and 20/50. Visual acuity around 20/200 may occur once the paracentral photoreceptor atrophy extends centrally, or due to the development of a macular hole or a secondary neovascular membrane. Progression of functional loss can often only be detected by mapping scotoma size or occurrence using microperimetry, while visual acuity may remain unchanged. PMID:25204528

  4. Increased resolution macular thickness mapping by OCT.

    PubMed

    Bernardes, Rui; Santos, Torcato; Cunha-Vaz, José

    2006-01-01

    Optical coherence tomography (OCT) poor mapping resolution has been pointed out as the biggest disadvantage of this technique when compared to others, e.g., retinal thickness analyzer. In this work we were able to solve this problem by developing an atlas of macular thickness of the human retina into which OCT scans were thereafter registered. This atlas is used to allow registering OCT scans from the Fast Macular Protocol, thus bringing OCT scans into the atlas coordinates, therefore correcting for misfixations, while simultaneously allowing to perform OCT inter-scan registration. From this initial registration, we were able to compute a thickness map into which Fast RNFL Protocol scans were merged, thus allowing for increased OCT mapping resolution. PMID:17946646

  5. 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

  6. Macular hole surgery using silicone oil tamponade

    PubMed Central

    Karia, N; Laidlaw, A; West, J; Ezra, E; Gregor, M

    2001-01-01

    BACKGROUND/AIMS—Most surgeons performing macular hole surgery using long acting gas recommend strict postoperative face down posturing for 10-15 days. Patients with chronic systemic illness such as arthritis may be unable to carry out this postoperative regime. Thus there is a need for alternative techniques that would eliminate such a regime. The authors review a series of patients who underwent macular hole surgery using silicone oil without any postoperative posturing.
METHODS—A retrospective case note review was performed of patients who had undergone macular hole surgery with silicone oil tamponade. The patients were unable to posture due to chronic illness and had stage 2, 3, or 4 full thickness macular holes. Removal of silicone oil performed with or without cataract surgery was arranged 3 months or more after surgery.
RESULTS—10 eyes of 10 patients underwent surgery. Duration of oil tamponade ranged from 3-9 months. Following oil removal the hole was closed in eight eyes (80%), of which only three showed any improvement in visual acuity (38%) even after cataract extraction. All eyes developed cataract to varying degrees and one eye developed raised intraocular pressure which settled after oil removal. A serious complication, endophthalmitis, occurred in one eye following removal of sutures after cataract extraction.
CONCLUSION—The anatomical results (80%) in this series are in keeping with those reported in other studies using gas tamponade. The visual results are disappointing and less rewarding than those obtained after successful surgery using gas tamponade.

 PMID:11673298

  7. [Epidemiology of age related macular degeneration].

    PubMed

    Leveziel, N; Delcourt, C; Zerbib, J; Dollfus, H; Kaplan, J; Benlian, P; Coscas, G; Souied, E H; Soubrane, G

    2009-06-01

    Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease. PMID:19515460

  8. Macular Bioaccelerometers on Earth and in Space

    NASA Technical Reports Server (NTRS)

    Ross, M. D.; Cutler, L.; Meyer, G.; Vazin, P.; Lam, T.

    1991-01-01

    Space flight offers the opportunity to study linear bioaccelerometers (vestibular maculas) in the virtual absence of a primary stimulus, gravitational acceleration. Macular research in space is particularly important to NASA because the bioaccelerometers are proving to be weighted neural networks in which information is distributed for parallel processing. Neural networks are plastic and highly adaptive to new environments. Combined morphological-physiological studies of maculas fixed in space and following flight should reveal macular adaptive responses to microgravity, and their time-course. Ground-based research, already begun, using computer-assisted, 3-dimensional reconstruction of macular terminal fields will lead to development of computer models of functioning maculas. This research should continue in conjunction with physiological studies, including work with multichannel electrodes. The results of such a combined effort could usher in a new era in understanding vestibular function on Earth and in space. They can also provide a rational basis for counter-measures to space motion sickness, which may prove troublesome as space voyager encounter new gravitational fields on planets, or must re-adapt to 1 g upon return to earth.

  9. An Improved Method for Extraction and Separation of Photosynthetic Pigments

    ERIC Educational Resources Information Center

    Katayama, Nobuyasu; Kanaizuka, Yasuhiro; Sudarmi, Rini; Yokohama, Yasutsugu

    2003-01-01

    The method for extracting and separating hydrophobic photosynthetic pigments proposed by Katayama "et al." ("Japanese Journal of Phycology," 42, 71-77, 1994) has been improved to introduce it to student laboratories at the senior high school level. Silica gel powder was used for removing water from fresh materials prior to extracting pigments by a…

  10. BASIS FOR ENHANCED BARRIER FUNCTION OF PIGMENTED SKIN

    PubMed Central

    Man, Mao-Qiang; Lin, Tzu-Kai; Santiago, Juan Luis; Celli, Anna; Zhong, Lily; Huang, Zhi-Ming; Roelandt, Truus; Hupe, Melanie; Sundberg, John P.; Silva, Kathleen A.; Crumrine, Debra; Martin-Ezquerra, Gemma; Trullas, Carles; Sun, Richard; Wakefield, Joan S.; Wei, Maria L.; Feingold, Kenneth R.; Mauro, Theodora M.; Elias, Peter M.

    2014-01-01

    Humans with darkly-pigmented skin display superior permeability barrier function in comparison to humans with lightly-pigmented skin. The reduced pH of the stratum corneum (SC) of darkly-pigmented skin could account for enhanced function, because acidifying lightly-pigmented human SC resets barrier function to darkly-pigmented levels. In SKH1 (non-pigmented) vs. SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J vs. SKH1 mice, correlating with a reduced pH in the lower SC that co-localizes with the extrusion of melanin granules. Darkly-pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate re-acidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly-pigmented-bearing human keratinocytes display enhanced barrier function in comparison to lightly-pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression. PMID:24732399

  11. Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration

    PubMed Central

    Brilliant, Murray H.; Vaziri, Kamyar; Connor, Thomas B.; Schwartz, Stephen G.; Carroll, Joseph J.; McCarty, Catherine A.; Schrodi, Steven J.; Hebbring, Scott J.; Kishor, Krishna S.; Flynn, Harry W.; Moshfeghi, Andrew A.; Moshfeghi, Darius M.; Fini, M. Elizabeth; McKay, Brian S.

    2016-01-01

    BACKGROUND Age-related macular degeneration (AMD) is a leading cause of visual loss among the elderly. A key cell type involved in AMD, the retinal pigment epithelium, expresses a G protein–coupled receptor that, in response to its ligand, L-DOPA, up-regulates pigment epithelia–derived factor, while down-regulating vascular endothelial growth factor. In this study we investigated the potential relationship between L-DOPA and AMD. METHODS We used retrospective analysis to compare the incidence of AMD between patients taking vs not taking L-DOPA. We analyzed 2 separate cohorts of patients with extensive medical records from the Marshfield Clinic (approximately 17,000 and approximately 20,000) and the Truven MarketScan outpatient and databases (approximately 87 million) patients. We used International Classification of Diseases, 9th Revision codes to identify AMD diagnoses and L-DOPA prescriptions to determine the relative risk of developing AMD and age of onset with or without an L-DOPA prescription. RESULTS In the retrospective analysis of patients without an L-DOPA prescription, AMD age of onset was 71.2, 71.3, and 71.3 in 3 independent retrospective cohorts. Age-related macular degeneration occurred significantly later in patients with an L-DOPA prescription, 79.4 in all cohorts. The odds ratio of developing AMD was also significantly negatively correlated by L-DOPA (odds ratio 0.78; confidence interval, 0.76–0.80; P <.001). Similar results were observed for neovascular AMD (P <.001). CONCLUSIONS Exogenous L-DOPA was protective against AMD. L-DOPA is normally produced in pigmented tissues, such as the retinal pigment epithelium, as a byproduct of melanin synthesis by tyrosinase. GPR143 is the only known L-DOPA receptor; it is therefore plausible that GPR143 may be a fruitful target to combat this devastating disease. PMID:26524704

  12. Investigating Mitochondria as a Target for Treating Age-Related Macular Degeneration

    PubMed Central

    Terluk, Marcia R.; Kapphahn, Rebecca J.; Soukup, Lauren M.; Gong, Hwee; Gallardo, Christopher; Montezuma, Sandra R.

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. Although the pathological mechanisms have not been definitively elucidated, evidence suggests a key role for mitochondrial (mt) dysfunction. The current study used our unique collection of human retinal samples graded for the donor's stage of AMD to address fundamental questions about mtDNA damage in the retina. To evaluate the distribution of mtDNA damage in the diseased retina, damage in the retinal pigment epithelium (RPE) and neural retina from individual donors were compared. To directly test a long-held belief that the macula is selectively damaged with AMD, RPE mtDNA damage was measured in the macula and peripheral sections from individual donors. Small segments of the entire mt genome were examined to determine whether specific regions are preferentially damaged. Our results show that mtDNA damage is limited to the RPE, equivalent mtDNA damage is found in the macular and peripheral RPE, and sites of damage are localized to regions of the mt genome that may impact mt function. These results provide a scientific basis for targeting the RPE mitochondria with therapies that protect and enhance mt function as a strategy for combating AMD. PMID:25948278

  13. Investigating mitochondria as a target for treating age-related macular degeneration.

    PubMed

    Terluk, Marcia R; Kapphahn, Rebecca J; Soukup, Lauren M; Gong, Hwee; Gallardo, Christopher; Montezuma, Sandra R; Ferrington, Deborah A

    2015-05-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. Although the pathological mechanisms have not been definitively elucidated, evidence suggests a key role for mitochondrial (mt) dysfunction. The current study used our unique collection of human retinal samples graded for the donor's stage of AMD to address fundamental questions about mtDNA damage in the retina. To evaluate the distribution of mtDNA damage in the diseased retina, damage in the retinal pigment epithelium (RPE) and neural retina from individual donors were compared. To directly test a long-held belief that the macula is selectively damaged with AMD, RPE mtDNA damage was measured in the macula and peripheral sections from individual donors. Small segments of the entire mt genome were examined to determine whether specific regions are preferentially damaged. Our results show that mtDNA damage is limited to the RPE, equivalent mtDNA damage is found in the macular and peripheral RPE, and sites of damage are localized to regions of the mt genome that may impact mt function. These results provide a scientific basis for targeting the RPE mitochondria with therapies that protect and enhance mt function as a strategy for combating AMD. PMID:25948278

  14. Choroidal ischemia and serous macular detachment associated with severe postoperative pain.

    PubMed

    Jung, Jee Woong; Lee, Dae Young; Nam, Dong Heun

    2008-06-01

    To report the association of a unilateral serous macular detachment with severe postoperative pain. A 71-year-old woman presented with a sudden decrease in vision in the right eye, seven days after a total knee replacement arthroplasty. The patient's history was unremarkable except for a severe pain greater than the visual analog scale of 8 points for about 2 days after surgery. Retinal examination showed a well differentiated serous detachment that was about 3.5 disc diameter in size and located in the macular area. Fluorecein angiography and indocyanine green angiography showed delayed perfusion of the choriocapillaris without leakage points in the early phase and persistent hypofluorescence with pooling of dye in the subretinal space in the late phase. There was a spontaneous resolution of the serous detachment and the choroidal changes with residual pigment epithelial changes. Severe postoperative pain may influence the sympathetic activity and introduce an ischemic injury with a focal, choroidal vascular compromise and secondary dysfunction of overlying RPE cells in select patients.

  15. Bicyclic [3.3.0]-Octahydrocyclopenta[c]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease.

    PubMed

    Cioffi, Christopher L; Racz, Boglarka; Freeman, Emily E; Conlon, Michael P; Chen, Ping; Stafford, Douglas G; Schwarz, Daniel M C; Zhu, Lei; Kitchen, Douglas B; Barnes, Keith D; Dobri, Nicoleta; Michelotti, Enrique; Cywin, Charles L; Martin, William H; Pearson, Paul G; Johnson, Graham; Petrukhin, Konstantin

    2015-08-13

    Antagonists of retinol-binding protein 4 (RBP4) impede ocular uptake of serum all-trans retinol (1) and have been shown to reduce cytotoxic bisretinoid formation in the retinal pigment epithelium (RPE), which is associated with the pathogenesis of both dry age-related macular degeneration (AMD) and Stargardt disease. Thus, these agents show promise as a potential pharmacotherapy by which to stem further neurodegeneration and concomitant vision loss associated with geographic atrophy of the macula. We previously disclosed the discovery of a novel series of nonretinoid RBP4 antagonists, represented by bicyclic [3.3.0]-octahydrocyclopenta[c]pyrrolo analogue 4. We describe herein the utilization of a pyrimidine-4-carboxylic acid fragment as a suitable isostere for the anthranilic acid appendage of 4, which led to the discovery of standout antagonist 33. Analogue 33 possesses exquisite in vitro RBP4 binding affinity and favorable drug-like characteristics and was found to reduce circulating plasma RBP4 levels in vivo in a robust manner (>90%). PMID:26181715

  16. Age-Related Macular Degeneration: Genetics and Biology.

    PubMed

    Kumaramanickavel, Govindasamy

    2016-01-01

    Age-related macular degeneration (AMD), widely prevalent across the globe, is a major stakeholder among adult visual morbidity and blindness, not only in the Western world but also in Asia. Several risk factors have been identified, including critical genetic factors, which were never imagined 2 decades ago. The etiopathogenesis is emerging to demonstrate that immune and complement-related inflammation pathway members chronically exposed to environmental insults could justifiably influence disease morbidity and treatment outcomes. Approximately half a dozen physiological and biochemical cascades are disrupted in the AMD disease genesis, eventually leading to the distortion and disruption of the subretinal space, subretinal pigment epithelium, and Bruch membrane, thus setting off chaos and disorder for signs and symptoms to manifest. Approximately 3 dozen genetic factors have so far been identified, including the recent ones, through powerful genomic technologies and large robust sample sizes. The noteworthy genetic variants (common and rare) are complement factor H, complement factor H-related genes 1 to 5, C3, C9, ARMS2/HTRA1, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2/KDR, and rare variants (show causal link) such as TIMP3, fibrillin, COL4A3, MMP19, and MMP9. Despite the enormous amount of scientific information generated over the years, diagnostic genetic or biomarker tests are still not available for clinicians to understand the natural course of the disease and its management in a patient. However, further research in the field should reduce this gap not only by aiding the clinician but also through the possibilities of clinical intervention with complement pathway-related inhibitors entering preclinical and clinical trials in the near future. PMID:27488064

  17. Progressive macular hypomelanosis among Egyptian patients: a clinicopathological study

    PubMed Central

    Selim, Mohamed Khaled; Ahmed, El-Shahat Farag; Abdelgawad, Mamdouh Morsy; El-Kamel, Mohammed Fawzy

    2011-01-01

    Background: Progressive macular hypomelanosis (PMH) is a disease of unclear etiology. Propionbacterium acnes (P. acnes) was claimed to be an etiological factor. Objectives: The purpose of this study was to document the clinicopathological features of PMH in Egyptian patients and to evaluate the therapeutic outcome. Methods: Patients with clinical features of PMH were recruited. Wood’s lamp examination, skin scrapings for fungi, and skin biopsy specimens were obtained. Biopsies were stained with hematoxylin and eosin, PAS, Fontana-Masson, and S100 protein. Patients received either narrow-band UVB (nbUVB) or nbUVB plus daily topical clindamycin 1% and benzoyl peroxide gel 5% (bcUVB). The period of active treatment was 14 weeks followed by a follow-up period of 24 weeks. Results: Twenty-nine patients were included. Microscopic evaluation of skin biopsy specimens showed no significant differences between lesional and normal skin. Fontana-Masson stained sections showed overall reduction of melanin granules in the basal layer of lesional skin only and S100 staining did not detect significant differences in the number of melanocytes in lesional and normal skin. Nearly complete repigmentation was reported in 10 patients treated with bcUVB compared to 9 patients treated with nbUVb with no significant differences between both groups after 14 weeks. Only 2 patients in each group retained the pigmentation and the remaining patients returned to the baseline color before treatment. Conclusions: This study documented the clinicopathological features of PMH among Egyptians. No permanently effective treatment is available. Further studies are needed to prove or disprove the pathogenic role of P. acnes in PMH. PMID:24396712

  18. Changes in pigment, spectral transmission and element content of pink chicken eggshells with different pigment intensity during incubation

    PubMed Central

    Yu, Yue; Li, Zhanming

    2016-01-01

    Objective. The objective of this study was to investigate changes in pigment, spectral transmission and element content of chicken eggshells with different intensities of pink pigment during the incubation period. We also investigated the effects of the region (small pole, equator and large pole) and pink pigment intensity of the chicken eggshell on the percent transmission of light passing through the chicken eggshells. Method. Eggs of comparable weight from a meat-type breeder (Meihuang) were used, and divided based on three levels of pink pigment (light, medium and dark) in the eggshells. During the incubation (0–21 d), the values of the eggshell pigment (ΔE, L∗, a∗, b∗) were measured. The percent transmission of light for different regions and intensities of eggshell pigmentation was measured by using the visible wavelength range of 380–780 nm. Result. Three measured indicators of eggshell color, ΔE, L∗ and a∗, did not change significantly during incubation. Compared with other regions and pigment intensities, eggshell at the small pole and with light pigmentation intensity showed the highest percent transmission of light. The transmission value varied significantly (P < 0.001) with incubation time. The element analysis of eggshells with different levels of pink pigment showed that the potassium content of the eggshells for all pigment levels decreased significantly during incubation. Conclusion. In summary, pigment intensity and the region of the eggshell influenced the percent transmission of light of eggshell. Differences in the spectral characteristics of different eggshells may influence the effects of photostimulation during the incubation of eggs. All of these results will be applicable for perfecting the design of light intensity for lighted incubation to improve productivity. PMID:27019785

  19. Changes in pigment, spectral transmission and element content of pink chicken eggshells with different pigment intensity during incubation.

    PubMed

    Yu, Yue; Li, Zhanming; Pan, Jinming

    2016-01-01

    Objective. The objective of this study was to investigate changes in pigment, spectral transmission and element content of chicken eggshells with different intensities of pink pigment during the incubation period. We also investigated the effects of the region (small pole, equator and large pole) and pink pigment intensity of the chicken eggshell on the percent transmission of light passing through the chicken eggshells. Method. Eggs of comparable weight from a meat-type breeder (Meihuang) were used, and divided based on three levels of pink pigment (light, medium and dark) in the eggshells. During the incubation (0-21 d), the values of the eggshell pigment (ΔE, L (∗), a (∗), b (∗)) were measured. The percent transmission of light for different regions and intensities of eggshell pigmentation was measured by using the visible wavelength range of 380-780 nm. Result. Three measured indicators of eggshell color, ΔE, L (∗) and a (∗), did not change significantly during incubation. Compared with other regions and pigment intensities, eggshell at the small pole and with light pigmentation intensity showed the highest percent transmission of light. The transmission value varied significantly (P < 0.001) with incubation time. The element analysis of eggshells with different levels of pink pigment showed that the potassium content of the eggshells for all pigment levels decreased significantly during incubation. Conclusion. In summary, pigment intensity and the region of the eggshell influenced the percent transmission of light of eggshell. Differences in the spectral characteristics of different eggshells may influence the effects of photostimulation during the incubation of eggs. All of these results will be applicable for perfecting the design of light intensity for lighted incubation to improve productivity.

  20. Age-related macular degeneration and the complement system.

    PubMed

    Khandhadia, S; Cipriani, V; Yates, J R W; Lotery, A J

    2012-02-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a complex multifactorial disease, and despite new advances in treatment, many patients still succumb to visual impairment. The complement pathway has been implicated in the pathogenesis of many diseases, and recently variants in several genes encoding complement pathway proteins have been associated with AMD. Complement proteins have been found in histological specimens of eyes with AMD. Altered levels of both intrinsic complement proteins and activated products have been found in the circulation of patients with AMD. Complement activation may be triggered by oxidative stress, resulting from retinal exposure to incoming light; indeed an inter-play between these two pathological processes seems to exist. Finally, complement inhibitors are currently being evaluated in clinical trials. This article reviews the role of the complement system in AMD, and the potential of complement inhibition in preventing the devastating blindness resulting from this disease.

  1. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. PMID:26572116

  2. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index.

  3. Spontaneous closure of macular hole following blunt trauma.

    PubMed

    Freitas-Neto, Clovis Arcoverde; Pigosso, Douglas; Pacheco, Katia Delalíbera; Pereira, Viviane Oliveira; Patel, Pranav; Freitas, Luiz Guilherme; Ávila, Marcos Pereira

    2016-01-01

    Ocular trauma can result in macular hole and it can lead to complete loss of central vision. We are reporting a case of traumatic macular hole associated with retinal hemorrhages and choroidal ruptures with spontaneous resolution and total vision recovery. PMID:27433039

  4. High glucose promotes the migration of retinal pigment epithelial cells through increased oxidative stress and PEDF expression.

    PubMed

    Farnoodian, Mitra; Halbach, Caroline; Slinger, Cassidy; Pattnaik, Bikash R; Sorenson, Christine M; Sheibani, Nader

    2016-09-01

    Defects in the outer blood-retinal barrier have significant impact on the pathogenesis of diabetic retinopathy and macular edema. However, the detailed mechanisms involved remain largely unknown. This is, in part, attributed to the lack of suitable animal and cell culture models, including those of mouse origin. We recently reported a method for the culture of retinal pigment epithelial (RPE) cells from wild-type and transgenic mice. The RPE cells are responsible for maintaining the integrity of the outer blood-retinal barrier whose dysfunction during diabetes has a significant impact on vision. Here we determined the impact of high glucose on the function of RPE cells. We showed that high glucose conditions resulted in enhanced migration and increased the level of oxidative stress in RPE cells, but minimally impacted their rate of proliferation and apoptosis. High glucose also minimally affected the cell-matrix and cell-cell interactions of RPE cells. However, the expression of integrins and extracellular matrix proteins including pigment epithelium-derived factor (PEDF) were altered under high glucose conditions. Incubation of RPE cells with the antioxidant N-acetylcysteine under high glucose conditions restored normal migration and PEDF expression. These cells also exhibited increased nuclear localization of the antioxidant transcription factor Nrf2 and ZO-1, reduced levels of β-catenin and phagocytic activity, and minimal effect on production of vascular endothelial growth factor, inflammatory cytokines, and Akt, MAPK, and Src signaling pathways. Thus high glucose conditions promote RPE cell migration through increased oxidative stress and expression of PEDF without a significant effect on the rate of proliferation and apoptosis. PMID:27440660

  5. Photooxidations in pigmented Blepharisma.

    PubMed

    GIESE, A C; ZEUTHEN, E

    1949-03-20

    1. Blepharisma undulans, a protozoan with a reddish pigment, shows increased oxygen consumption under the influence of light. 2. If the light intensity is high, the animals are killed during a burst of oxygen consumption. 3. If the blepharismas are first bleached by exposure to light of low intensity they show only slightly increased oxygen consumption under the influence of light and they are not killed. 4. A preparation in which the animals are killed by heat still shows the increase in oxygen consumption on illumination with brilliant light. The supernatant solution does so as well, as does an alcohol extract of the dye. 5. The conclusion is drawn that the blepharismas are killed during photooxidation of the pigment, but the mechanism of action is not clear. Several possibilities are considered in the discussion.

  6. Acetazolamide for cystoid macular oedema in Bietti crystalline retinal dystrophy.

    PubMed

    Broadhead, Geoffrey K; Chang, Andrew A

    2014-04-01

    Bietti crystalline retinal dystrophy is a rare, inherited disorder whose hallmark is the presence of retinal crystal deposits associated with later chorioretinal degeneration. This condition may rarely be complicated by the development of cystoid macular oedema leading to rapid visual decline. Currently, treatment options for this complication of Bietti dystrophy are limited and the visual prognosis is poor. Here, we present a case of cystoid macular oedema associated with Bietti dystrophy that was successfully diagnosed using multimodal imaging techniques including optical coherence tomography and fluorescein angiography. These modalities confirmed the diagnosis of macular oedema and excluded other possible causes of oedema such as choroidal neovascularisation. In this patient, cystoid macular oedema was resolved with oral acetazolamide therapy, a treatment that has not been previously reported in this context. Acetazolamide treatment resulted in oedema resolution and improvement in visual function, and can be considered a therapeutic option for other patients with Bietti dystrophy who develop cystoid macular oedema.

  7. Macular edema in branch retinal vein occlusion: types and treatment.

    PubMed

    Jalkh, A E; Trempe, C L

    1989-01-01

    In this study of branch retinal vein occlusion, we distinguished between cystoid macular edema caused by increased capillary pressure and noncystoid edema due to hard exudates in the macula caused by chronic leakage from vascular abnormalities in the posterior pole or midperiphery. We performed laser photocoagulation in 51 eyes with cystoid macular edema to achieve focal narrowing of the retinal arterioles perfusing the macular area affected by the cystoid edema; good anatomic and functional results were achieved in 40 of these eyes (78%). In 25 of the five eyes, the treated segment of the retinal arteriole was outside the area of macular edema; results were successful in 19 of these eyes (76%). In 14 eyes with noncystoid exudative macular edema, we performed laser photocoagulation to the vascular abnormalities; good anatomic and functional results were obtained in 12 of these (86%). PMID:2927879

  8. MCP-1–Activated Monocytes Induce Apoptosis in Human Retinal Pigment Epithelium

    PubMed Central

    Yang, Dongli; Elner, Susan G.; Chen, Xun; Field, Matthew G.; Petty, Howard R.

    2011-01-01

    Purpose. The inflammatory response in age-related macular degeneration (AMD) is characterized by mononuclear leukocyte infiltration of the outer blood–retina barrier formed by the retinal pigment epithelium (RPE). A key mechanistic element in AMD progression is RPE dysfunction and apoptotic cell loss. The purpose of this study was to evaluate whether monocyte chemoattractant protein (MCP)-1–activated monocytes induce human RPE apoptosis and whether Ca2+ and reactive oxygen species (ROS) are involved in this process. Methods. A cell-based fluorometric assay was used to measure intracellular Ca2+ concentrations ([Ca2+]i) in RPE cells loaded with fluorescent Ca2+ indicator. Intracellular RPE ROS levels were measured by using the 5- and 6-chloromethyl-2′,7′-dichlorodihydrofluorescence diacetate acetyl ester (CM-H2DCFDA) assay. RPE apoptosis was evaluated by activated caspase-3, Hoechst staining, and apoptosis ELISA. Results. MCP-1–activated human monocytes increased [Ca2+]i, ROS levels, and apoptosis in RPE cells, all of which were inhibited by 8-bromo-cyclic adenosine diphosphoribosyl ribose (8-Br-cADPR), an antagonist of cADPR. Although the ROS scavengers pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) significantly inhibited ROS production and apoptosis induced by activated monocytes, they did not affect induced Ca2+ levels. The induced Ca2+ levels and apoptosis in RPE cells were inhibited by an antibody against cluster of differentiation antigen 14 (CD14), an adhesion molecule expressed by these cells. Conclusions. These results indicate that CD14, Ca2+, and ROS are involved in activated monocyte-induced RPE apoptosis and that cADPR contributes to these changes. Understanding the complex interactions among CD14, cADPR, Ca2+, and ROS may provide new insights and treatments of retinal diseases, including AMD. PMID:21447688

  9. Prodigiosin from Vibrio sp. DSM 14379; a new UV-protective pigment.

    PubMed

    Borić, Maja; Danevčič, Tjaša; Stopar, David

    2011-10-01

    Pigments such as melanin, scytonemin and carotenoids protect microbial cells against the harmful effects of ultraviolet (UV) radiation. The role in UV protection has never been assigned to the prodigiosin pigment. In this work, we demonstrate that prodigiosin provides a significant level of protection against UV stress in Vibrio sp. DSM 14379. In the absence of pigment production, Vibrio sp. was significantly more susceptible to UV stress, and there was no difference in UV survival between the wild-type strain and non-pigmented mutant. The pigment's protective role was more important at higher doses of UV irradiation and correlated with pigment concentration in the cell. Pigmented cells survived high UV exposure (324 J/m(2)) around 1,000-fold more successfully compared to the non-pigmented mutant cells. Resistance to UV stress was conferred to the non-pigmented mutant by addition of exogenous pigment extract to the growth medium. A level of UV protection equivalent to that exhibited by the wild-type strain was attained by the non-pigmented mutant once the prodigiosin concentration had reached comparable levels to those found in the wild-type strain. In co-culture experiments, prodigiosin acted as a UV screen, protecting both the wild-type and non-pigmented mutants. Our results suggest a new ecophysiological role for prodigiosin.

  10. Dissecting pigment architecture of individual photosynthetic antenna complexes in solution.

    PubMed

    Wang, Quan; Moerner, W E

    2015-11-10

    Oligomerization plays a critical role in shaping the light-harvesting properties of many photosynthetic pigment-protein complexes, but a detailed understanding of this process at the level of individual pigments is still lacking. To study the effects of oligomerization, we designed a single-molecule approach to probe the photophysical properties of individual pigment sites as a function of protein assembly state. Our method, based on the principles of anti-Brownian electrokinetic trapping of single fluorescent proteins, step-wise photobleaching, and multiparameter spectroscopy, allows pigment-specific spectroscopic information on single multipigment antennae to be recorded in a nonperturbative aqueous environment with unprecedented detail. We focus on the monomer-to-trimer transformation of allophycocyanin (APC), an important antenna protein in cyanobacteria. Our data reveal that the two chemically identical pigments in APC have different roles. One (α) is the functional pigment that red-shifts its spectral properties upon trimer formation, whereas the other (β) is a "protective" pigment that persistently quenches the excited state of α in the prefunctional, monomer state of the protein. These results show how subtleties in pigment organization give rise to functionally important aspects of energy transfer and photoprotection in antenna complexes. The method developed here should find immediate application in understanding the emergent properties of other natural and artificial light-harvesting systems.

  11. [Treatment of exudative age-related macular degeneration].

    PubMed

    Yuzawa, M

    2000-12-01

    I PROPHYLACTIC TREATMENT: We followed 75 eyes contralateral to eyes with exudative age-related macular degeneration (AMD), using indocyanine green angiography (IA), for more than one year. Hyperfluorescent areas in the late phase of IA were seen in 19 eyes at the initial examination, and in 25 eyes during follow-up. Exudative AMD developed in 9 of the 25 eyes. Using timetable analysis, we estimated that 11% of these 27 eyes developed AMD within one year and 55% within three years. The hyperfluorescent areas seen on IA appeared to be latent choroidal neovascularization (CNV) under the retinal pigment epithelium. We propose that photocoagulation aimed at hyperfluorescent areas should be considered in such cases. We performed prophylactic laser photocoagulation in 21 eyes, which were then followed up for at least six months. These eyes all had 10 or more serous drusen within 1,500 microns of the fovea and did not show hyperfluorescence, suggesting latent CNV in the late phase of IA. The majority or a small fraction of the serous drusen disappeared in 48% and 18% of the 21 eyes, respectively. CNV appeared adjacent to the laser scar in one eye (5%). Judging from these results, it is important to establish a method of definitively abolishing drusen and preventing the development of CNV. II TREATMENT OF CNV: Of 229 eyes which showed occult CNV in fluorescein angiography (FA), 124 eyes (54%) showed classic CNV outside the fovea on IA. One hundred and two of the 124 eyes (45%) underwent laser photocoagulation. We evaluated indocyanine green guided laser photocoagulation of extrafoveal CNV in 139 eyes. The success rate was 81% at 3 months after laser photocoagulation. This was estimated using timetable analyses to have decreased to 78% at one year and 71% at three years. Eighty percent of successfully treated eyes showed maintained or improved visual acuity. These results did not differ significantly from those obtained with laser photocoagulation based on FA findings. When

  12. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.

    PubMed

    Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

    2012-09-01

    Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy.

  13. Raman Spectroscopy of Microbial Pigments

    PubMed Central

    Edwards, Howell G. M.; Oren, Aharon

    2014-01-01

    Raman spectroscopy is a rapid nondestructive technique providing spectroscopic and structural information on both organic and inorganic molecular compounds. Extensive applications for the method in the characterization of pigments have been found. Due to the high sensitivity of Raman spectroscopy for the detection of chlorophylls, carotenoids, scytonemin, and a range of other pigments found in the microbial world, it is an excellent technique to monitor the presence of such pigments, both in pure cultures and in environmental samples. Miniaturized portable handheld instruments are available; these instruments can be used to detect pigments in microbiological samples of different types and origins under field conditions. PMID:24682303

  14. Black-pigmented sputum

    PubMed Central

    Martínez-Girón, Rafael; Mosquera-Martínez, Joaquín; Martínez-Torre, Santiago

    2013-01-01

    Black-pigmented sputum, also called “melanoptysis,” is a symptom that may be observed in certain pathologies such us coal workers’ pneumoconiosis (anthracosis). The cavitation and liquefaction of a fibrosed mass by an infectious process (tuberculosis, infections by anaerobes, etc.) or by ischemic necrosis may cause expectoration of a blackish secretion. We report the case of a patient with labor precedents as a coal worker, from whom abundant black sputum was obtained in the course of an incidental expectoration. Cyto-histological findings are shown and a differential diagnosis is established. PMID:24648674

  15. Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments

    PubMed Central

    Hofmann, Thomas; Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Rey Moreno, Maria; Neubauer, Nicole; Wohlleben, Wendel; Gröters, Sibylle; Wiench, Karin; Veith, Ulrich; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-01-01

    Abstract Diketopyrrolopyrroles (DPP) are a relatively new class of organic high-performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m3 as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID:27387137

  16. Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments.

    PubMed

    Hofmann, Thomas; Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Rey Moreno, Maria; Neubauer, Nicole; Wohlleben, Wendel; Gröters, Sibylle; Wiench, Karin; Veith, Ulrich; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-08-01

    Diketopyrrolopyrroles (DPP) are a relatively new class of organic high-performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m(3) as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID:27387137

  17. Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation.

    PubMed

    Wang, Junhua; Westenskow, Peter D; Fang, Mingliang; Friedlander, Martin; Siuzdak, Gary

    2016-10-28

    Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic 'fingerprint' of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques. A number of classes of metabolites were consistently dysregulated during degeneration: vitamin A analogues, fatty acid amides, long-chain polyunsaturated fatty acids, acyl carnitines and several phospholipid species. For the first time, a distinct temporal trend of several important metabolites including DHA (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), all-trans-retinal and its toxic end-product N-retinyl-N-retinylidene-ethanolamine were observed between healthy and dystrophic retinas. In this study, metabolomics was further used to determine the temporal effects of the therapeutic intervention of grafting stem cell-derived retinal pigment epithelium (RPE) in dystrophic retinas, which significantly prevented photoreceptor atrophy in our previous studies. The result revealed that lipid levels such as phosphatidylethanolamine in eyes were restored in those animals receiving the RPE grafts. In conclusion, this study provides insight into the metabolomics of retinal degeneration, and further understanding of the efficacy of RPE transplantation.This article is part of the themed issue 'Quantitative mass spectrometry'. PMID:27644974

  18. Photo-damage, photo-protection and age-related macular degeneration.

    PubMed

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD.

  19. The potential role of amyloid β in the pathogenesis of age-related macular degeneration

    PubMed Central

    Yoshida, Takeshi; Ohno-Matsui, Kyoko; Ichinose, Shizuko; Sato, Tetsuji; Iwata, Nobuhisa; Saido, Takaomi C.; Hisatomi, Toshio; Mochizuki, Manabu; Morita, Ikuo

    2005-01-01

    Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid β (Aβ) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Aβ on cultured human RPE cells as well as ocular findings in neprilysin gene–disrupted mice, which leads to an increased deposition Aβ. The results showed that Aβ treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Aβ-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene–disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Aβ accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Aβ reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD. PMID:16167083

  20. Photo-damage, photo-protection and age-related macular degeneration.

    PubMed

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD. PMID:26198091

  1. The effect of hypoxia upon macular recovery time in normal humans.

    PubMed

    Brinchmann-Hansen, O; Myhre, K

    1989-12-01

    Bright light illumination (photostress) of the macula produces a negative after-image in the form of a central scotoma. The time needed for restoring normal visual acuity function, "macular recovery time," may be measured using a nyctometer. We have measured the recovery in 30 normal men, aged 18 to 23 years, at sea level and at 8,000 ft (n = 10), 15,000 ft (n = 10), and 18,000 ft (n = 10) of simulated altitudes in a low pressure chamber. The degree of initial recovery (the first 30-40 s) was unaffected by hypoxia equivalent to 8,000, 15,000, and 18,000 ft. The recovery at 2 min was impaired by hypoxia at an altitude of 18,000 ft (p = 0.009) but not at 8,000 ft or 15,000 ft. The initial phase of recovery may represent the neural phase of macular function and appears to be more resistant to hypoxia than the recovery at 2 min, the latter probably being dominated by photochemical recovery. The study establishes a critical level of hypoxia where complete recovery of macular sensitivity is not achieved.

  2. Influence of anti-VEGF about cardiovascular biomarkers in age related macular degeneration.

    PubMed

    Manresa, N; Mulero, J; Losada, M; Zafrilla, P

    2015-02-01

    Systemic VEGF inhibition disrupts endothelial homeostasis and accelerates the atherogenesis, suggesting that these events contribute to the clinical cardiovascular adverse events of VEGF-inhibiting therapies. The objective of the current study was to analyze the effect of anti-VEGF therapy on cardiovascular risk factors in patients with exudative age related macular degeneration. A total of 73 patients with exudative age related macular degeneration (without previous anti-VEGF therapy) were treated with two anti-VEGF: Ranibizumab and Pegaptanib sodium. The follow up was 6 months. The following parameters were determined before and after treatment: homocysteine, lipids (total cholesterol, triglycerides, HDL-c, LDL-c), C-Reactive Protein and fibrinogen. There were not statistically significant differences in parameters studied before and after treatment with both Pegaptanib sodium and Ranibizumab, except C-Reactive Protein. Of all patients analyzed, only 3 of them have initially C-Reactive Protein levels above normal levels and after antiangiogenic therapy, there was a significant increase in C-Reactive Protein. We have not found results in our study who to suspect that treatment with anti-VEGF in the patients with exudative age related macular degeneration increases cardiovascular risk predictors. However, after therapy was increased the CRP and fibrinogen may mean that anti-VEGF contribute an alteration of endothelial homeostasis in exudative AMD.

  3. Iris angiography in cystoid macular edema after cataract extraction.

    PubMed

    Kottow, M; Hendrickson, P

    1975-07-01

    Iris angiography was performed on eight patients (nine eyes), who had cystoid macular edema postcataract extraction. The fundus fluorescein angiographies showed typical star-shaped, multiloculated staining of the macular area. The iris angiographies demonstrated moderate to massive leakage of dye from the iris, and possibly leakage of ciliary body vessels into the anterior chamber, thus evidencing the until now suspected but undocumented fact that fluorescein leakage is not restricted to the fundus vessels. These data tend to support the idea that this type of macular edema is due to a vascular abnormality, and not to altered vitreous mechanics.

  4. Vision loss without Amsler grid abnormalities in macular subretinal neovascularization.

    PubMed

    Roy, M S

    1985-01-01

    An 87-year-old woman, with known atrophic senile macular degeneration in one eye, had isolated decreased reading ability while Amsler grid testing was normal. This led to the early diagnosis of macular subretinal neovascularization in the other eye. Thus patients at high risk for neovascular macular degeneration should be made aware of possible subtle changes in vision as well as abnormalities in the Amsler grid. Regular visual acuity check and careful biomicroscopic examination of the macula should be part of each follow-up examination.

  5. Protective effects of retinoid x receptors on retina pigment epithelium cells.

    PubMed

    Ayala-Peña, Victoria Belén; Pilotti, Fiorella; Volonté, Yanel; Rotstein, Nora P; Politi, Luis E; German, Olga Lorena

    2016-06-01

    Age-related macular degeneration (AMD) is among the main pathologies leading to blindness in adults and has currently no cure or effective treatment. Selective apoptosis of retina pigment epithelial (RPE) cells results in the progressive loss of photoreceptor neurons, with the consequent gradual vision loss. Oxidative stress plays an important role in this process. We have previously determined that activation of RXRs protects rat photoreceptor neurons from oxidative stress-induced apoptosis. In this study we investigated whether RXR ligands prevented apoptosis in an RPE cell line, D407 cells, exposed to hydrogen peroxide (H2O2). H2O2 induced apoptosis of D407 cells, promoting p65NFκB nuclear translocation, increasing Bax mRNA expression, activating caspase-3 and altering cell morphology. We show, for the first time, that HX630, a RXR pan-agonist, protected D407 cells from H2O2-induced apoptosis, preventing p65NFκB nuclear translocation, increasing Bclxl and PPARγ mRNA levels and simultaneously decreasing Bax mRNA levels and caspase-3 activation. Pretreatment with a RXR antagonist blocked HX630 protection. LG100754, which binds RXRs but only activates heterodimers and is an antagonist of RXR homodimers, also had a protective effect. In addition, only agonists known to bind to RXR/PPARγ were protective. As a whole, our results suggest that RXR activation protects RPE cells from oxidative stress-induced apoptosis and this protection might involve signaling through a heterodimeric receptor, such as RXR/PPARγ. These data also imply that RXR agonists might provide potential pharmacological tools for treating retina degenerative diseases. PMID:26883505

  6. Absence of collagen XVIII in mice causes age-related insufficiency in retinal pigment epithelium proteostasis.

    PubMed

    Kivinen, Niko; Felszeghy, Szabolcs; Kinnunen, Aino I; Setälä, Niko; Aikio, Mari; Kinnunen, Kati; Sironen, Reijo; Pihlajaniemi, Taina; Kauppinen, Anu; Kaarniranta, Kai

    2016-08-01

    Collagen XVIII has the structural properties of both collagen and proteoglycan. It has been found at the basement membrane/stromal interface where it is thought to mediate their attachment. Endostatin, a proteolytic fragment from collagen XVIII C-terminal end has been reported to possess anti-angiogenic properties. Age-related vision loss in collagen XVIII mutant mice has been accompanied with a pathological accumulation of deposits under the retinal pigment epithelium (RPE). We have recently demonstrated that impaired proteasomal and autophagy clearance are associated with the pathogenesis of age-related macular degeneration. This study examined the staining levels of proteasomal and autophagy markers in the RPE of different ages of the Col18a1 (-/-) mice. Eyes from 3, 6-7, 10-13 and 18 months old mice were enucleated and embedded in paraffin according to the routine protocol. Sequential 5 μm-thick parasagittal samples were immunostained for proteasome and autophagy markers ubiquitin (ub), SQSTM1/p62 and beclin-1. The levels of immunopositivity in the RPE cells were evaluated by confocal microscopy. Collagen XVIII knock-out mice had undergone age-related RPE degeneration accompanied by an accumulation of drusen-like deposits. Ub protein conjugate staining was prominent in both RPE cytoplasm and extracellular space whereas SQSTM1/p62 and beclin-1 stainings were clearly present in the basal part of RPE cell cytoplasm in the Col18a1 (-/-) mice. SQSTM1/p62 displayed mild extracellular space staining. Disturbed proteostasis regulated by collagen XVIII might be responsible for the RPE degeneration, increased protein aggregation, ultimately leading to choroidal neovascularization. PMID:27125427

  7. Protective effects of retinoid x receptors on retina pigment epithelium cells.

    PubMed

    Ayala-Peña, Victoria Belén; Pilotti, Fiorella; Volonté, Yanel; Rotstein, Nora P; Politi, Luis E; German, Olga Lorena

    2016-06-01

    Age-related macular degeneration (AMD) is among the main pathologies leading to blindness in adults and has currently no cure or effective treatment. Selective apoptosis of retina pigment epithelial (RPE) cells results in the progressive loss of photoreceptor neurons, with the consequent gradual vision loss. Oxidative stress plays an important role in this process. We have previously determined that activation of RXRs protects rat photoreceptor neurons from oxidative stress-induced apoptosis. In this study we investigated whether RXR ligands prevented apoptosis in an RPE cell line, D407 cells, exposed to hydrogen peroxide (H2O2). H2O2 induced apoptosis of D407 cells, promoting p65NFκB nuclear translocation, increasing Bax mRNA expression, activating caspase-3 and altering cell morphology. We show, for the first time, that HX630, a RXR pan-agonist, protected D407 cells from H2O2-induced apoptosis, preventing p65NFκB nuclear translocation, increasing Bclxl and PPARγ mRNA levels and simultaneously decreasing Bax mRNA levels and caspase-3 activation. Pretreatment with a RXR antagonist blocked HX630 protection. LG100754, which binds RXRs but only activates heterodimers and is an antagonist of RXR homodimers, also had a protective effect. In addition, only agonists known to bind to RXR/PPARγ were protective. As a whole, our results suggest that RXR activation protects RPE cells from oxidative stress-induced apoptosis and this protection might involve signaling through a heterodimeric receptor, such as RXR/PPARγ. These data also imply that RXR agonists might provide potential pharmacological tools for treating retina degenerative diseases.

  8. Involvement of endoplasmic reticulum stress in all-trans-retinal-induced retinal pigment epithelium degeneration.

    PubMed

    Li, Jie; Cai, Xianhui; Xia, Qingqing; Yao, Ke; Chen, Jingmeng; Zhang, Yanli; Naranmandura, Hua; Liu, Xin; Wu, Yalin

    2015-01-01

    Excess accumulation of endogenous all-trans-retinal (atRAL) contributes to degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells, and plays a role in the etiologies of age-related macular degeneration (AMD) and Stargardt's disease. In this study, we reveal that human RPE cells tolerate exposure of up to 5 µM atRAL without deleterious effects, but higher concentrations are detrimental and induce cell apoptosis. atRAL treatment significantly increased production of intracellular reactive oxygen species (ROS) and up-regulated mRNA expression of Nrf2, HO-1, and γ-GCSh within RPE cells, thereby causing oxidative stress. ROS localized to mitochondria and endoplasmic reticulum (ER). ER-resident molecular chaperone BiP, a marker of ER stress, was up-regulated at the translational level, and meanwhile, the PERK-eIF2α-ATF4 signaling pathway was activated. Expression levels of ATF4, CHOP, and GADD34 in RPE cells increased in a concentration-dependent manner after incubation with atRAL. Salubrinal, a selective inhibitor of ER stress, alleviated atRAL-induced cell death. The antioxidant N-acetylcysteine (NAC) effectively blocked RPE cell loss and ER stress activation, suggesting that atRAL-induced ROS generation is responsible for RPE degeneration and is an early trigger of ER stress. Furthermore, the mitochondrial transmembrane potential was lost after atRAL exposure, and was followed by caspase-3 activation and poly (ADP-ribose) polymerase cleavage. The results demonstrate that atRAL-driven ROS overproduction-induced ER stress is involved in cellular mitochondrial dysfunction and apoptosis of RPE cells. PMID:25331497

  9. Absence of collagen XVIII in mice causes age-related insufficiency in retinal pigment epithelium proteostasis.

    PubMed

    Kivinen, Niko; Felszeghy, Szabolcs; Kinnunen, Aino I; Setälä, Niko; Aikio, Mari; Kinnunen, Kati; Sironen, Reijo; Pihlajaniemi, Taina; Kauppinen, Anu; Kaarniranta, Kai

    2016-08-01

    Collagen XVIII has the structural properties of both collagen and proteoglycan. It has been found at the basement membrane/stromal interface where it is thought to mediate their attachment. Endostatin, a proteolytic fragment from collagen XVIII C-terminal end has been reported to possess anti-angiogenic properties. Age-related vision loss in collagen XVIII mutant mice has been accompanied with a pathological accumulation of deposits under the retinal pigment epithelium (RPE). We have recently demonstrated that impaired proteasomal and autophagy clearance are associated with the pathogenesis of age-related macular degeneration. This study examined the staining levels of proteasomal and autophagy markers in the RPE of different ages of the Col18a1 (-/-) mice. Eyes from 3, 6-7, 10-13 and 18 months old mice were enucleated and embedded in paraffin according to the routine protocol. Sequential 5 μm-thick parasagittal samples were immunostained for proteasome and autophagy markers ubiquitin (ub), SQSTM1/p62 and beclin-1. The levels of immunopositivity in the RPE cells were evaluated by confocal microscopy. Collagen XVIII knock-out mice had undergone age-related RPE degeneration accompanied by an accumulation of drusen-like deposits. Ub protein conjugate staining was prominent in both RPE cytoplasm and extracellular space whereas SQSTM1/p62 and beclin-1 stainings were clearly present in the basal part of RPE cell cytoplasm in the Col18a1 (-/-) mice. SQSTM1/p62 displayed mild extracellular space staining. Disturbed proteostasis regulated by collagen XVIII might be responsible for the RPE degeneration, increased protein aggregation, ultimately leading to choroidal neovascularization.

  10. The peripheral clock regulates human pigmentation.

    PubMed

    Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

    2015-04-01

    Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies. PMID:25310406

  11. The peripheral clock regulates human pigmentation.

    PubMed

    Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

    2015-04-01

    Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies.

  12. Cosmetic tattoo pigment reaction.

    PubMed

    Greywal, Tanya; Cohen, Philip R

    2016-01-01

    BackgroundCutaneous reactions to tattoos are most commonly granulomatous or lichenoid.PurposeWe describe a woman who developed a lymphocytic reaction following a cosmetic tattoo procedure with black dye. The reaction occurred not only at the site of the tattoos (eyebrows and eyelash lines), but also in non-tattooed skin (bilateral malar cheeks).Methods and MaterialsWe reviewed PubMed for the following terms: cosmetic, dye, granuloma, granulomatous, lichenoid, lymphocytic, perivascular, pigment, pseudolymphoma, reaction, and tattoo. We also reviewed papers containing these terms and their references.ResultsHistopathologic examination of the left eyebrow and left cheek punch biopsies showed predominantly a perivascular lymphocytic reaction secondary to exogenous tattoo pigment.ConclusionsPerivascular lymphocytic reaction is an uncommonly described complication of tattooing. Our patient had an atypical presentation since she had no prior tattoos, became symptomatic only a few days after the procedure, reacted to black dye, and involved skin both within and outside the confines of the tattoos. Her symptoms and lesions resolved after treatment with systemic and topical corticosteroids and oral antihistamines. PMID:27617722

  13. Effect of Hemodialysis on Retinal Thickness in Patients with Diabetic Retinopathy, with and without Macular Edema, Using Optical Coherence Tomography

    PubMed Central

    Azem, Nur; Spierer, Oriel; Shaked, Meital; Neudorfer, Meira

    2014-01-01

    Background. Effects of hemodialysis (HD) treatment on retinal thickness and macular edema are unclear. Objective. To evaluate changes in retinal thickness using optical coherence tomography (OCT) in end stage renal disease (ESRD) patients with diabetic retinopathy (DR), with and without diabetic macular edema (DME), undergoing HD. Methods. Nonrandomized prospective study. Forty eyes of DR patients with ESRD treated with HD were divided into two groups: patients with macular edema and patients without macular edema. Both eyes were analyzed. Patients underwent an ophthalmic examination including OCT measurements of retinal thickness, blood albumin and hemoglobin A1C levels, blood pressure, and body weight, 30 minutes before and after HD. Results. We found no significant effects of HD on retinal thickness among patients both with and without DME. The former showed a trend towards reduction in retinal thickness in foveal area following HD, while the latter showed an increase. There was no correlation between retinal thickness and mean blood pressure, weight, kinetic model value—Kt/V, glycemic hemoglobin, or albumin levels before and after HD. Conclusions. HD has no significant effect on retinal thickness among patients with or without DME. Further studies on larger cohorts and repeated OCT examinations are needed to confirm the preliminary findings in this study. PMID:25298889

  14. Effect of Hemodialysis on Retinal Thickness in Patients with Diabetic Retinopathy, with and without Macular Edema, Using Optical Coherence Tomography.

    PubMed

    Azem, Nur; Spierer, Oriel; Shaked, Meital; Neudorfer, Meira

    2014-01-01

    Background. Effects of hemodialysis (HD) treatment on retinal thickness and macular edema are unclear. Objective. To evaluate changes in retinal thickness using optical coherence tomography (OCT) in end stage renal disease (ESRD) patients with diabetic retinopathy (DR), with and without diabetic macular edema (DME), undergoing HD. Methods. Nonrandomized prospective study. Forty eyes of DR patients with ESRD treated with HD were divided into two groups: patients with macular edema and patients without macular edema. Both eyes were analyzed. Patients underwent an ophthalmic examination including OCT measurements of retinal thickness, blood albumin and hemoglobin A1C levels, blood pressure, and body weight, 30 minutes before and after HD. Results. We found no significant effects of HD on retinal thickness among patients both with and without DME. The former showed a trend towards reduction in retinal thickness in foveal area following HD, while the latter showed an increase. There was no correlation between retinal thickness and mean blood pressure, weight, kinetic model value-Kt/V, glycemic hemoglobin, or albumin levels before and after HD. Conclusions. HD has no significant effect on retinal thickness among patients with or without DME. Further studies on larger cohorts and repeated OCT examinations are needed to confirm the preliminary findings in this study. PMID:25298889

  15. Comparative chromatography of chloroplast pigment

    NASA Technical Reports Server (NTRS)

    Grandolfo, M.; Sherma, J.; Strain, H. H.

    1969-01-01

    Methods for isolation of low concentration pigments of the cocklebur species are described. The methods entail two step chromatography so that the different sorption properties of the various pigments in varying column parameters can be utilized. Columnar and thin layer methods are compared. Many conditions influence separability of the chloroplasts.

  16. Nonphotosynthetic pigments as potential biosignatures.

    PubMed

    Schwieterman, Edward W; Cockell, Charles S; Meadows, Victoria S

    2015-05-01

    Previous work on possible surface reflectance biosignatures for Earth-like planets has typically focused on analogues to spectral features produced by photosynthetic organisms on Earth, such as the vegetation red edge. Although oxygenic photosynthesis, facilitated by pigments evolved to capture photons, is the dominant metabolism on our planet, pigmentation has evolved for multiple purposes to adapt organisms to their environment. We present an interdisciplinary study of the diversity and detectability of nonphotosynthetic pigments as biosignatures, which includes a description of environments that host nonphotosynthetic biologically pigmented surfaces, and a lab-based experimental analysis of the spectral and broadband color diversity of pigmented organisms on Earth. We test the utility of broadband color to distinguish between Earth-like planets with significant coverage of nonphotosynthetic pigments and those with photosynthetic or nonbiological surfaces, using both 1-D and 3-D spectral models. We demonstrate that, given sufficient surface coverage, nonphotosynthetic pigments could significantly impact the disk-averaged spectrum of a planet. However, we find that due to the possible diversity of organisms and environments, and the confounding effects of the atmosphere and clouds, determination of substantial coverage by biologically produced pigments would be difficult with broadband colors alone and would likely require spectrally resolved data.

  17. Nonphotosynthetic Pigments as Potential Biosignatures

    PubMed Central

    Cockell, Charles S.; Meadows, Victoria S.

    2015-01-01

    Abstract Previous work on possible surface reflectance biosignatures for Earth-like planets has typically focused on analogues to spectral features produced by photosynthetic organisms on Earth, such as the vegetation red edge. Although oxygenic photosynthesis, facilitated by pigments evolved to capture photons, is the dominant metabolism on our planet, pigmentation has evolved for multiple purposes to adapt organisms to their environment. We present an interdisciplinary study of the diversity and detectability of nonphotosynthetic pigments as biosignatures, which includes a description of environments that host nonphotosynthetic biologically pigmented surfaces, and a lab-based experimental analysis of the spectral and broadband color diversity of pigmented organisms on Earth. We test the utility of broadband color to distinguish between Earth-like planets with significant coverage of nonphotosynthetic pigments and those with photosynthetic or nonbiological surfaces, using both 1-D and 3-D spectral models. We demonstrate that, given sufficient surface coverage, nonphotosynthetic pigments could significantly impact the disk-averaged spectrum of a planet. However, we find that due to the possible diversity of organisms and environments, and the confounding effects of the atmosphere and clouds, determination of substantial coverage by biologically produced pigments would be difficult with broadband colors alone and would likely require spectrally resolved data. Key Words: Biosignatures—Exoplanets—Halophiles—Pigmentation—Reflectance spectroscopy—Spectral models. Astrobiology 15, 341–361. PMID:25941875

  18. Role of inflammation in previously untreated macular edema with branch retinal vein occlusion

    PubMed Central

    2014-01-01

    Background The association of inflammatory factors and the aqueous flare value with macular edema in branch retinal vein occlusion (BRVO) patients remains unclear. The relationship between the aqueous flare value and the vitreous fluid levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble VEGF receptor-2 (sVEGFR-2) was evaluated to investigate the role of inflammation in BRVO associated with macular edema. Aqueous flare values and the vitreous levels of VEGF, IL-6, MCP-1, sICAM-1, and sVEGFR-2 were compared between previously untreated patients with BRVO and patients with macular hole (MH). Methods Vitreous samples were obtained from 45 patients during vitreoretinal surgery (28 patients with BRVO and 17 with MH), and the levels of VEGF, IL-6, MCP-1, sICAM-1, and sVEGFR-2 were measured by enzyme-linked immunosorbent assay. Retinal ischemia was evaluated by measuring the area of capillary non-perfusion using fluorescein angiography and the Scion Image program. Aqueous flare values were measured with a laser flare meter and macular edema was examined by optical coherence tomography. Results The median aqueous flare value was significantly higher in the BRVO group (12.1 photon counts/ms) than in the MH group (4.5 photon counts/ms, P < 0.001). There were significant correlations between the aqueous flare value and the vitreous levels of VEGF, IL-6, MCP-1, and sICAM-1 in the BRVO group (ρ = 0.54, P = 0.005; ρ = 0.56, P = 0.004; ρ = 0.52, P = 0.006; and ρ = 0.47, P = 0.015, respectively). The aqueous flare value was also significantly correlated with the foveal thickness in the BRVO group (ρ = 0.40, P = 0.037). Conclusions Inflammation may induce an increase of vascular permeability and disrupt the blood-aqueous barrier via release of inflammatory factors (VEGF, IL-6, MCP-1, and sICAM-1) in BRVO patients

  19. New directions in phthalocyanine pigments

    NASA Technical Reports Server (NTRS)

    Trinh, Diep VO

    1994-01-01

    Phthalocyanines have been used as a pigment in coatings and related applications for many years. These pigments are some of the most stable organic pigments known. The phthalo blue and green pigments have been known to be ultraviolet (UV) stable and thermally stable to over 400 C. These phthalocyanines are both a semiconductor and photoconductor, exhibiting catalytic activity and photostabilization capability of polymers. Many metal free and metallic phthalocyanine derivatives have been prepared. Development of the new classes of phthalocyanine pigment could be used as coating on NASA spacecraft material such as glass to decrease the optical degradation from UV light, the outside of the space station modules for UV protection, and coating on solar cells to increase lifetime and efficiency.

  20. Laser-induced macular holes demonstrate impaired choroidal perfusion

    NASA Astrophysics Data System (ADS)

    Brown, Jeremiah, Jr.; Allen, Ronald D.; Zwick, Harry; Schuschereba, Steven T.; Lund, David J.; Stuck, Bruce E.

    2003-06-01

    Choroidal perfusion was evaluated following the creation of a laser induced macular hole in a nonhuman primate model. Two Rhesus monkeys underwent macular exposures delivered by a Q-switched Nd:YAG laser. The lesions were evaluated with fluorescein angiography and indocyanine green (ICG) angiography . Each lesion produced vitreous hemorrhage and progressed to a full thickness macular hole. ICG angiography revealed no perfusion of the choriocapillaris beneath the lesion centers. Histopathologic evaluation showed replacement of the choriocapillaris with fibroblasts and connective tissue. Nd:YAG, laser-induced macular holes result in long term impairment of choroidal perfusion at the base of the hole due to choroidal scarring and obliteration of the choriocapillaris.

  1. Differences in spectral absorption properties between active neovascular macular degeneration and mild age related maculopathy.

    PubMed

    Balaskas, Konstantinos; Nourrit, Vincent; Dinsdale, Michelle; Henson, David B; Aslam, Tariq

    2013-05-01

    This study examines the differences in spectral absorption properties between the maculae of patients with active neovascular macular degeneration and those with early age related maculopathy (ARM). Patients attending for management of neovascular age related macular degeneration (AMD) underwent multispectral imaging with a system comprising of a modified digital fundus camera coupled with a 250-W tungsten-halogen lamp and a liquid crystal fast-tuneable filter. Images were obtained at 8 wavelengths between 496 and 700 nm. Aligned images were used to generate a DLA (differential light absorption, a measure of spectral absorption properties) map of the macular area. DLA maps were generated for both eyes of 10 sequential patients attending for anti-vascular endothelial growth factor injections. Each of these patients had active leaking neovascular AMD in one eye and early ARM or milder disease in the fellow eye. Eyes with neovascular AMD demonstrated lower average levels of DLA compared with their fellow eyes with early ARM (p=0.037, t test). The significant difference in DLA demonstrates the potential of multispectral imaging for differentiating the two pathologies non-invasively. PMID:23137662

  2. Prevalence and patterns of comorbid cognitive impairment in low vision rehabilitation (LVR) for macular disease

    PubMed Central

    Whitson, Heather E.; Ansah, Deidra; Whitaker, Diane; Potter, Guy; Cousins, Scott W.; MacDonald, Heather; Pieper, Carl F.; Landerman, Lawrence; Steffens, David C.; Cohen, Harvey J.

    2009-01-01

    The prevalence of comorbid cognitive impairment among older adults referred to LVR for macular disease is unknown. We performed cognitive testing on 101 adults aged 65 years or older with macular disease who were referred to The Duke LVR Clinic between September 2007 and March 2008. Scores on the telephone interview for cognitive status-modified (TICS-m) ranged from 7 to 44, with 18.8% of scores below an established cutoff for cognitive impairment (≤ 27) and an additional 27.7% of scores considered marginal (28-30). On letter fluency, 46% of participants scored at least 1 × S.D. below the mean for their age, gender, race, and education level, and 18% of participants scored at least 2 × S.D. below their demographic mean. On logical memory, 26% of participants scored at least 1 × S.D. below the mean for their age group and race and 6% scored at least 2 × S.D. below their demographic mean. High prevalence of cognitive impairment, with particular difficulty in verbal fluency and verbal memory, may compromise the success of low vision rehabilitation interventions among macular disease patients. Additional work is needed to develop strategies to maximize function in older adults with this common comorbidity. PMID:19427045

  3. Macular dazzling test on normal subjects.

    PubMed Central

    Gomez-Ulla, F; Louro, O; Mosquera, M

    1986-01-01

    The macular dazzling test was performed on 240 healthy eyes, classified into six groups according to the ages of the subjects. The test was used to assess both long distance and short distance vision with a simultaneous study of the influence of mydriasis and miosis. The MDT is a test easy to perform, requires a minimum of co-operation by the subject, and gives repeatable results. The MDT values increase significantly as the age of the subject increases. The sex of the subject has no influence on it, and there are no significant differences between a subject's right and left eyes. Mydriasis does not affect the MDT, but miosis reduces the recovery period. All the values are statistically greater for long distance vision than for short distance vision. PMID:3954979

  4. Update on corticosteroids for diabetic macular edema.

    PubMed

    Schwartz, Stephen G; Scott, Ingrid U; Stewart, Michael W; Flynn, Harry W

    2016-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME. PMID:27660409

  5. Update on corticosteroids for diabetic macular edema

    PubMed Central

    Schwartz, Stephen G; Scott, Ingrid U; Stewart, Michael W; Flynn, Harry W

    2016-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME. PMID:27660409

  6. Update on corticosteroids for diabetic macular edema

    PubMed Central

    Schwartz, Stephen G; Scott, Ingrid U; Stewart, Michael W; Flynn, Harry W

    2016-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME.

  7. [Epidemiology of age-related macular degeneration].

    PubMed

    Brandl, C; Stark, K J; Wintergerst, M; Heinemann, M; Heid, I M; Finger, R P

    2016-09-01

    Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies. PMID:27541733

  8. Pseudophakic cystoid macular edema: update 2016

    PubMed Central

    Grzybowski, Andrzej; Sikorski, Bartosz L; Ascaso, Francisco J; Huerva, Valentín

    2016-01-01

    Pseudophakic cystoid macular edema (PCME) is the most common complication of cataract surgery, leading in some cases to a decrease in vision. Although the pathogenesis of PCME is not completely understood, the contribution of postsurgical inflammation is generally accepted. Consequently, anti-inflammatory medicines, including steroids and nonsteroidal anti-inflammatory drugs, have been postulated as having a role in both the prophylaxis and treatment of PCME. However, the lack of a uniformly accepted PCME definition, conflicting data on some risk factors, and the scarcity of studies comparing the role of nonsteroidal anti-inflammatory drugs to steroids in PCME prevention make the problem of PCME one of the puzzles of ophthalmology. This paper presents an updated review on the pathogenesis, risk factors, and use of anti-inflammatory drugs in PCME that reflect current research and practice.

  9. Pseudophakic cystoid macular edema: update 2016

    PubMed Central

    Grzybowski, Andrzej; Sikorski, Bartosz L; Ascaso, Francisco J; Huerva, Valentín

    2016-01-01

    Pseudophakic cystoid macular edema (PCME) is the most common complication of cataract surgery, leading in some cases to a decrease in vision. Although the pathogenesis of PCME is not completely understood, the contribution of postsurgical inflammation is generally accepted. Consequently, anti-inflammatory medicines, including steroids and nonsteroidal anti-inflammatory drugs, have been postulated as having a role in both the prophylaxis and treatment of PCME. However, the lack of a uniformly accepted PCME definition, conflicting data on some risk factors, and the scarcity of studies comparing the role of nonsteroidal anti-inflammatory drugs to steroids in PCME prevention make the problem of PCME one of the puzzles of ophthalmology. This paper presents an updated review on the pathogenesis, risk factors, and use of anti-inflammatory drugs in PCME that reflect current research and practice. PMID:27672316

  10. 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

  11. [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES].

    PubMed

    Gorohivets, N A; Vedmedeva, E V

    2016-01-01

    Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly. PMID:27281924

  12. [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES].

    PubMed

    Gorohivets, N A; Vedmedeva, E V

    2016-01-01

    Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly.

  13. Altered levels of LIL3 isoforms in Arabidopsis lead to disturbed pigment-protein assembly and chlorophyll synthesis, chlorotic phenotype and impaired photosynthetic performance.

    PubMed

    Lohscheider, Jens N; Rojas-Stütz, Marc C; Rothbart, Maxi; Andersson, Ulrica; Funck, Dietmar; Mendgen, Kurt; Grimm, Bernhard; Adamska, Iwona

    2015-10-01

    Light-harvesting complex (LHC)-like (LIL) proteins contain two transmembrane helices of which the first bears a chlorophyll (Chl)-binding motif. They are widespread in photosynthetic organisms, but almost nothing is known about their expression and physiological functions. We show that two LIL3 paralogues (LIL3:1 and LIL3:2) in Arabidopsis thaliana are expressed in photosynthetically active tissues and their expression is differentially influenced by light stress. Localization studies demonstrate that both isoforms are associated with subcomplexes of LHC antenna of photosystem II. Transgenic plants with reduced amounts of LIL3:1 exhibited a slightly impaired growth and have reduced Chl and carotenoid contents as compared to wild-type plants. Ectopic overexpression of either paralogue led to a developmentally regulated switch to co-suppression of both LIL3 isoforms, resulting in a circular chlorosis of the leaf rosettes. Chlorotic sectors show severely diminished levels of LIL3 isoforms and other proteins, and thylakoid morphology was changed. Additionally, the levels of enzymes involved in Chl biosynthesis are altered in lil3 mutant plants. Our data support a role of LIL3 paralogues in the regulation of Chl biosynthesis under light stress and under standard growth conditions as well as in a coordinated ligation of newly synthesized and/or rescued Chl molecules to their target apoproteins.

  14. The orf162b Sequence of Rhodobacter capsulatus Encodes a Protein Required for Optimal Levels of Photosynthetic Pigment-Protein Complexes

    PubMed Central

    Aklujkar, Muktak; Harmer, Andrea L.; Prince, Roger C.; Beatty, J. Thomas

    2000-01-01

    The orf162b sequence, the second open reading frame 3′ of the reaction center (RC) H protein gene puhA in the Rhodobacter capsulatus photosynthesis gene cluster, is shown to be transcribed from a promoter located 5′ of puhA. A nonpolar mutation of orf162b was generated by replacing most of the coding region with an antibiotic resistance cartridge. Although the mutant strain initiated rapid photosynthetic growth, growth slowed progressively and cultures often entered a pseudostationary phase. The amounts of the RC and light harvesting complex I (LHI) in cells obtained from such photosynthetic cultures were abnormally low, but these deficiencies were less severe when the mutant was grown to a pseudostationary phase induced by low aeration in the absence of illumination. The orf162b mutation did not significantly affect the expression of a pufB::lacZ translationally in-frame gene fusion under the control of the puf promoter, indicating normal transcription and translation of RC and LHI genes. Spontaneous secondary mutations in the strain with the orf162b disruption resulted in a bypass of the photosynthetic growth retardation and reduced the level of light harvesting complex II. These results and the presence of sequences similar to orf162b in other species indicate that the Orf162b protein is required for normal levels of the photosynthetic apparatus in purple photosynthetic bacteria. PMID:10986247

  15. Effect of Amaranthus Pigments on Quality Characteristics of Pork Sausages

    PubMed Central

    Zhou, Cunliu; Zhang, Lin; Wang, Hui; Chen, Conggui

    2012-01-01

    The objective of this investigation was to evaluate the possibility of substituting Amaranthus pigments for nitrates in the of manufacture pork sausage. Five treatments of pork sausages (5% fat) with two levels of sodium nitrite (0 and 0.015%), or three levels (0.1%, 0.2% and 0.3%) of pigments extracted from red Amaranthus were produced. The addition of Amaranthus pigments resulted in the significant increase of a* values, sensory color, flavor and overall acceptance scores, but the significant reduction of b* values, TBA values and VBN values (p<0.05). Based mainly on the results of overall acceptance during 29 d storage, it could be concluded that Amaranthus pigments showed a potential as nitrite alternative for pork sausage manufacture. PMID:25049507

  16. Dissecting pigment architecture of individual photosynthetic antenna complexes in solution

    PubMed Central

    Wang, Quan; Moerner, W. E.

    2015-01-01

    Oligomerization plays a critical role in shaping the light-harvesting properties of many photosynthetic pigment−protein complexes, but a detailed understanding of this process at the level of individual pigments is still lacking. To study the effects of oligomerization, we designed a single-molecule approach to probe the photophysical properties of individual pigment sites as a function of protein assembly state. Our method, based on the principles of anti-Brownian electrokinetic trapping of single fluorescent proteins, step-wise photobleaching, and multiparameter spectroscopy, allows pigment-specific spectroscopic information on single multipigment antennae to be recorded in a nonperturbative aqueous environment with unprecedented detail. We focus on the monomer-to-trimer transformation of allophycocyanin (APC), an important antenna protein in cyanobacteria. Our data reveal that the two chemically identical pigments in APC have different roles. One (α) is the functional pigment that red-shifts its spectral properties upon trimer formation, whereas the other (β) is a “protective” pigment that persistently quenches the excited state of α in the prefunctional, monomer state of the protein. These results show how subtleties in pigment organization give rise to functionally important aspects of energy transfer and photoprotection in antenna complexes. The method developed here should find immediate application in understanding the emergent properties of other natural and artificial light-harvesting systems. PMID:26438850

  17. Natural pigments and sacred art

    NASA Astrophysics Data System (ADS)

    Kelekian, Lena, ,, Lady

    2010-05-01

    Since the dawn of mankind, cavemen has expressed himself through art. The earliest known cave paintings date to some 32,000 years ago and used 4 colours derived from the earth. These pigments were iron oxides and known as ochres, blacks and whites. All pigments known by the Egyptians, the Greeks, the Romans and Renaissance man were natural and it was not until the 18th century that synthetic pigments were made and widely used. Until that time all art, be it sacred or secular used only natural pigments, of which the preparation of many have been lost or rarely used because of their tedious preparation. As a geologist, a mineralogist and an artist specializing in iconography, I have been able to rediscover 89 natural pigments extracted from minerals. I use these pigments to paint my icons in the traditional Byzantine manner and also to restore old icons, bringing back their glamour and conserving them for years to come. The use of the natural pigments in its proper way also helps to preserve the traditional skills of the iconographer. In the ancient past, pigments were extremely precious. Many took an exceedingly long journey to reach the artists, and came from remote countries. Research into these pigments is the work of history, geography and anthropology. It is an interesting journey in itself to discover that the blue aquamarines came from Afghanistan, the reds from Spain, the greens Africa, and so on. In this contribution I will be describing the origins, preparation and use of some natural pigments, together with their history and provenance. Additionally, I will show how the natural pigments are used in the creation of an icon. Being a geologist iconographer, for me, is a sacrement that transforms that which is earthly, material and natural into a thing of beauty that is sacred. As bread and wine in the Eucharist, water during baptism and oil in Holy Union transmit sanctification to the beholder, natural pigments do the same when one considers an icon. The

  18. Propofol Decreases Endoplasmic Reticulum Stress–Mediated Apoptosis in Retinal Pigment Epithelial Cells

    PubMed Central

    Xu, Yue; Zhang, Ting; Zhang, Shaochong

    2016-01-01

    Age-related macular degeneration (AMD) is the major cause of loss of sight globally. There is currently no effective treatment available. Retinal pigment epithelial (RPE) cells are an important part of the outer blood-retina barrier and their death is a determinant of AMD. Propofol, a common clinically used intravenous anesthetic agent, has been shown to act as an efficacious neuroprotective agent with antioxidative and anti-inflammatory properties in vivo and in vitro. However, little is known about its effects on RPE cells. The purpose of our research was to investigate whether propofol could protect RPE cells from apoptosis through endoplasmic reticulum (ER) stress–dependent pathways. To this end, prior to stimulation with thapsigargin (TG), ARPE-19 cells were pretreated with varying concentrations of propofol. A protective effect of propofol in TG-treated ARPE-9 was apparent, TUNEL and flow cytometric assays showed decreased apoptosis. We further demonstrated that propofol pretreatment attenuated or inhibited the effects caused by TG, such as upregulation of Bax, BiP, C/EBP homologous protein (CHOP), active caspase 12, and cleaved caspase 3, and downregulation of Bcl2. It also decreased the TG-induced levels of ER stress–related molecules such as p-PERK, p-eIF2α, and ATF4. Furthermore, it downregulated the expression of nuclear factor κB (NF-κB). This study elucidated novel propofol-induced cellular mechanisms for antiapoptotic activities in RPE cells undergoing ER stress and demonstrated the potential value of using propofol in the treatment of AMD. PMID:27311010

  19. Involvement of TonEBP/NFAT5 in osmoadaptative response of human retinal pigmented epithelial cells to hyperosmolar stress

    PubMed Central

    Libert, Sarah; Willermain, François; Weber, Célia; Bryla, Angélic; Salik, Dany; Gregoire, Françoise; Bolaky, Nargis; Caspers, Laure; Perret, Jason

    2016-01-01

    Purpose: Macular edema, a frequently encountered complication of diabetic retinopathy (DR), results from alterations of the blood retinal barrier (BRB) and leads to modifications of the retinal pigmented epithelium (RPE) functions. Osmolar changes of the surrounding medium could be responsible for modifications of the RPE functions leading to disturbance of retinal homeostasis. The expression, activation and function of the key hyperosmolar response factor Tonicity Enhancer Binding Protein (TonEBP also called nuclear factor of activated T-cell 5 - NFTA5) was investigated in ARPE-19 cells, derived from human RPE, in response to hyperosmolar stimulation. Methods: ARPE-19 cells were exposed to hyperosmolar medium. TonEBP mRNA and protein levels were quantified by qRT-PCR and semi-quantitative Western blot. TonEBP nuclear translocation was investigated by immunofluorescence. TonEBP transactivation activity was measured using a reported plasmid containing TonEBP binding sites. Results: In response to hyperosmolar stimulation of ARPE-19 cells, a dose-dependent increase in TonEBP mRNA and protein levels, as well as TonEBP nuclear translocation were observed. TonEBP transactivation activity was further demonstrated using a reporter plasmid containing TonEBP binding sites. A dominant negative form of TonEBP abolished NaCl-induced increase in TonEBP transactivation activity, and inhibited the increase of the target genes aldose reductase and sodium-dependent taurine transporter mRNA levels. SB203580, an inhibitor of two of the p38 protein kinase’s isoforms (p38α and p38β) inhibited the TonEBP nuclear translocation and transactivation activity in ARPE-19 cells exposed to hyperosmolar stimulation. Conclusions: Our data demonstrates the involvement of TonEBP in the mechanisms responsible for osmoadaptation to hyperosmolar stress in RPE cells. Given the emerging role of TonEBP in different pathological pathways, these data open new perspectives for the analysis of the

  20. Low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular diseases: a pilot study.

    PubMed

    Vingolo, Enzo M; Salvatore, Serena; Cavarretta, Sonia

    2009-06-01

    Macular disease is one of the main causes of visual impairment. We studied the efficacy of low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular disease. Five patients were enrolled (3 female and 2 male, mean age 53.8 years) and a total of 9 eyes was examined: 2 eyes with vitelliform dystrophy, 1 with a post-traumatic macular scar, 2 with Stargardt disease, 2 with myopic macular degeneration, 2 with cone dystrophy. All the patients underwent the following tests: visual acuity, reading speed, fixation test, MP-1 microperimetry. Low-vision rehabilitation, which lasted 10 weeks, consisted of 10 training sessions of 10 min for each eye, performed once a week using the MP-1 biofeedback examination. Statistical analysis was performed using Student's t-test. p values less than 0.05 were considered statistically significant. After training all patients displayed an improvement in visual acuity, fixation behaviour, retinal sensitivity and reading speed. Fixation behaviour within the 2 degrees diameter circle improved and was statistically significant for reading speed (p = 0.01). Reading speed improved from a mean value of 64.3 to 92 words/min. Our results show that audio feedback can, by increasing attentional modulation, help the brain to fix the final preferred retinal locus. Audio feedback facilitates stimuli transmission between intraretinal neurons as well as between the retina and brain, which is where the highest level of stimuli processing occurs, thereby probably supporting a "remapping phenomenon".

  1. Cardiovascular Risk Factors and Age-related Macular Degeneration: The Los Angeles Latino Eye Study

    PubMed Central

    Fraser-Bell, Samantha; Wu, Joanne; Klein, Ronald; Azen, Stanley P.; Hooper, Claire; Foong, Athena W. P.; Varma, Rohit

    2008-01-01

    Purpose To assess the association of cardiovascular risk factors, ocular perfusion pressure with early and advanced age-related macular degeneration (AMD) in Latinos. Design Population-based, cross-sectional study. Methods Data were collected from a population-based sample of self-identified adult Latinos using standardized protocols for assessing blood pressure and intraocular pressure (IOP) measurement and stereoscopic macular photography. Hypertension was defined as either a history of hypertension or systolic blood pressure (SBP) >140mmHg +/− diastolic blood pressure (DBP) ≥85mmHg. Ocular perfusion pressure (OPP) was defined as the difference between mean arterial blood pressure and IOP. AMD was diagnosed from photographic grading by masked trained graders. Logistic regression was used to assess associations. Results Gradable retinal photographs were available in 5875 participants. After adjusting for age, sex, and cigarette smoking, higher DBP and uncontrolled diastolic hypertension were associated with exudative AMD (Odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1−2.8; and OR, 3.3; CI, 1.2−9.3, respectively). Higher OPP was associated with a decreased risk of GA (OR, 0.4 per 10mmHg; CI, 0.3−0.5). Low pulse pressure was associated with a lower risk of exudative AMD (OR, 0.2; CI, 0.1−0.6). Obesity was associated with increased retinal pigment (OR, 1.6; CI, 1.0−2.3). Conclusion These data suggest that in Latinos cardiovascular risk factors may play a role in advanced AMD. Given that Latinos have a high prevalence of cardiovascular risk factors, an intervention aimed at reducing these risk factors may also have a beneficial impact on the risk of having early and advanced AMD. PMID:18222193

  2. Automated diagnosis of Age-related Macular Degeneration using greyscale features from digital fundus images.

    PubMed

    Mookiah, Muthu Rama Krishnan; Acharya, U Rajendra; Koh, Joel E W; Chandran, Vinod; Chua, Chua Kuang; Tan, Jen Hong; Lim, Choo Min; Ng, E Y K; Noronha, Kevin; Tong, Louis; Laude, Augustinus

    2014-10-01

    Age-related Macular Degeneration (AMD) is one of the major causes of vision loss and blindness in ageing population. Currently, there is no cure for AMD, however early detection and subsequent treatment may prevent the severe vision loss or slow the progression of the disease. AMD can be classified into two types: dry and wet AMDs. The people with macular degeneration are mostly affected by dry AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These lesions are identified by manual inspection of fundus images by the ophthalmologists. It is a time consuming, tiresome process, and hence an automated diagnosis of AMD screening tool can aid clinicians in their diagnosis significantly. This study proposes an automated dry AMD detection system using various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS) bispectra features, Fractional Dimension (FD), and Gabor wavelet features extracted from greyscale fundus images. The features are ranked using t-test, Kullback-Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance (CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking methods in order to select optimum features and classified into normal and AMD classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers. The performance of the proposed system is evaluated using private (Kasturba Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) datasets. The proposed system yielded the highest average classification accuracies of 90.19%, 95.07% and 95% with 42, 54 and 38 optimal ranked features using SVM classifier for private, ARIA and STARE datasets respectively. This automated AMD detection system can be used for mass fundus image screening and aid clinicians by making better use of their expertise on selected images that

  3. Macular optical coherence tomography findings and GPR143 mutations in patients with ocular albinism.

    PubMed

    Sepúlveda-Vázquez, H E; Villanueva-Mendoza, C; Zenteno, J C; Villegas-Ruiz, V; Pelcastre-Luna, E; García-Aguirre, G

    2014-10-01

    The aim of this study was to describe macular findings using spectral-domain optical coherence tomography (SD-OCT) in patients with ocular albinism (OA) and their carrier mothers, and to identify the frequency of GPR143 gene mutations in these patients. The study included five patients with a clinical diagnosis of OA. SD-OCT of the macular area was performed in both patients and their mothers. The anatomical characteristics of the macula and retinal pigment epithelium (RPE), patterns of autofluorescence and infrared imaging were analyzed. Polymerase chain reaction amplification of the complete coding sequence of GPR 143 was performed and subsequently analyzed by direct sequencing in patients and their possible carrier mothers. SD-OCT images revealed the presence of inner retinal layers in the fovea, an abnormal disposition of the Henle layer and a lack of thickening in the perifoveal area. We found increased thickness in the RPE to the outer segment and in the outer segment to the outer nuclear layer that is associated with increased visual acuity. Autofluorescence images revealed an absence of normal hipoautofluorescence in the fovea. No changes were observed in the images of their carrier mothers. Mutation screening and sequence analysis of the GPR 143 gene revealed a novel pathological mutation in two patients. Abnormalities in the macula were observed in all patients. SD-OCT is a useful tool for the assessment of patients with OA. No changes were observed in the SD-OCT of carrier mothers. Only two patients had the GPR143 gene mutation. PMID:24526317

  4. Nutritional Risk Factors for Age-Related Macular Degeneration

    PubMed Central

    Ersoy, Lebriz; Lechanteur, Yara T.; Hoyng, Carel B.; Kirchhof, Bernd; den Hollander, Anneke I.

    2014-01-01

    Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10−6; 2–6x/week: OR: 1.67, P = 7.98 × 10−5) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2–6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD. PMID:25101280

  5. Dermoscopic findings and histological correlation of the acral volar pigmented maculae in Laugier-Hunziker syndrome.

    PubMed

    Sendagorta, Elena; Feito, Marta; Ramírez, Paloma; Gonzalez-Beato, María; Saida, Toshiaki; Pizarro, Angel

    2010-11-01

    Laugier-Hunziker syndrome (LHS) is an acquired, benign, macular hyperpigmentation of the lips and oral mucosa, often associated with pigmentation of the nails. Volar acral maculae on the palms and fingertips of patients affected by LHS are a typical feature of this rare entity. Dermoscopic examination of these maculae has been described in a previous report, in which authors found a parallel-furrow pattern. We describe two cases in which a parallel-ridge pattern (PRP) was found on the dermoscopic examination of the pigmented acral lesions. Histological examination showed increased melanin in basal keratinocytes, which was most prominent in those located at the crista intermedia profunda, that is, in the epidermal rete ridges underlying the surface ridges. In our study, dermoscopic features of the pigmented maculae found on LHS differed from those previously described. In addition, by means of this case report, the histological features of these lesions are described for the first time, showing an excellent correlation with dermoscopy. The reported cases prove that although the PRP is very specific of melanoma, it is also possible to find it in benign lesions. Therefore, we must be familiar with the differential diagnosis of PRP, and take into consideration the clinical context in which we find it. Further studies are needed to increase our knowledge on the histological and dermoscopic features of acral pigmented maculae of LHS.

  6. Relative Pigment Composition and Remote Sensing Reflectance of Caribbean Shallow-Water Corals.

    PubMed

    Torres-Pérez, Juan L; Guild, Liane S; Armstrong, Roy A; Corredor, Jorge; Zuluaga-Montero, Anabella; Polanco, Ramón

    2015-01-01

    Reef corals typically contain a number of pigments, mostly due to their symbiotic relationship with photosynthetic dinoflagellates. These pigments usually vary in presence and concentration and influence the spectral characteristics of corals. We studied the variations in pigment composition among seven Caribbean shallow-water Scleractinian corals by means of High Performance Liquid Chromatography (HPLC) analysis to further resolve the discrimination of corals. We found a total of 27 different pigments among the coral species, including some alteration products of the main pigments. Additionally, pigments typically found in endolithic algae were also identified. A Principal Components Analysis and a Hierarchical Cluster Analysis showed the separation of coral species based on pigment composition. All the corals were collected under the same physical environmental conditions. This suggests that pigment in the coral's symbionts might be more genetically-determined than influenced by prevailing physical conditions of the reef. We further investigated the use of remote sensing reflectance (Rrs) as a tool for estimating the total pigment concentration of reef corals. Depending on the coral species, the Rrs and the total symbiont pigment concentration per coral tissue area correlation showed 79.5-98.5% confidence levels demonstrating its use as a non-invasive robust technique to estimate pigment concentration in studies of coral reef biodiversity and health. PMID:26619210

  7. Relative Pigment Composition and Remote Sensing Reflectance of Caribbean Shallow-Water Corals

    PubMed Central

    Torres-Pérez, Juan L.; Guild, Liane S.; Armstrong, Roy A.; Corredor, Jorge; Zuluaga-Montero, Anabella; Polanco, Ramón

    2015-01-01

    Reef corals typically contain a number of pigments, mostly due to their symbiotic relationship with photosynthetic dinoflagellates. These pigments usually vary in presence and concentration and influence the spectral characteristics of corals. We studied the variations in pigment composition among seven Caribbean shallow-water Scleractinian corals by means of High Performance Liquid Chromatography (HPLC) analysis to further resolve the discrimination of corals. We found a total of 27 different pigments among the coral species, including some alteration products of the main pigments. Additionally, pigments typically found in endolithic algae were also identified. A Principal Components Analysis and a Hierarchical Cluster Analysis showed the separation of coral species based on pigment composition. All the corals were collected under the same physical environmental conditions. This suggests that pigment in the coral’s symbionts might be more genetically-determined than influenced by prevailing physical conditions of the reef. We further investigated the use of remote sensing reflectance (Rrs) as a tool for estimating the total pigment concentration of reef corals. Depending on the coral species, the Rrs and the total symbiont pigment concentration per coral tissue area correlation showed 79.5–98.5% confidence levels demonstrating its use as a non-invasive robust technique to estimate pigment concentration in studies of coral reef biodiversity and health. PMID:26619210

  8. Effects of ambient and elevated CO2 on growth, chlorophyll fluorescence, photosynthetic pigments, antioxidants, and secondary metabolites of Catharanthus roseus (L.) G Don. grown under three different soil N levels.

    PubMed

    Singh, Aradhana; Agrawal, Madhoolika

    2015-03-01

    Catharanthus roseus L. plants were grown under ambient (375 ± 30 ppm) and elevated (560 ± 25 ppm) concentrations of atmospheric CO2 at different rates of N supply (without supplemental N, 0 kg N ha(-1); recommended N, 50 kg N ha(-1); and double recommended N, 100 kg N ha(-1)) in open top chambers under field condition. Elevated CO2 significantly increased photosynthetic pigments, photosynthetic efficiency, and organic carbon content in leaves at recommended (RN) and double recommended N (DRN), while significantly decreased total nitrogen content in without supplemental N (WSN). Activities of superoxide dismutase, catalase, and ascorbate peroxidase were declined, while glutathione reductase, peroxidase, and phenylalanine-ammonia lyase were stimulated under elevated CO2. However, the responses of the above enzymes were modified with different rates of N supply. Elevated CO2 significantly reduced superoxide production rate, hydrogen peroxide, and malondialdehyde contents in RN and DRN. Compared with ambient, total alkaloids content increased maximally at recommended level of N, while total phenolics in WSN under elevated CO2. Elevated CO2 stimulated growth of plants by increasing plant height and numbers of branches and leaves, and the magnitude of increment were maximum in DRN. The study suggests that elevated CO2 has positively affected plants by increasing growth and alkaloids production and reducing the level of oxidative stress. However, the positive effects of elevated CO2 were comparatively lesser in plants grown under limited N availability than in moderate and higher N availability. Furthermore, the excess N supply in DRN has stimulated the growth but not the alkaloids production under elevated CO2.

  9. Reduced macular function in ABCA4 carriers

    PubMed Central

    2015-01-01

    carriers demonstrated reduced macular function measured by mERG along with none to subtle and even extensive morphological retinal changes. The c.768 G>T, c.5461–10T>C, and c.319 C>T mutations were associated with the most deviant ERGs, including both significant reduction of mERG amplitudes and prolongation of mERG ITs, as well as with reduced amplitude or delayed IT for the 30 Hz flicker ffERG in a few cases. They may therefore be considered serious mutations. The c.5917delG and c.4469 G>A mutations were associated with milder or no macular alteration. Long-term follow-up of these and other ABCA4 carriers may be of importance to elucidate the role of ABCA4 mutations in age-related macular degeneration. Moreover, improved knowledge of separate ABCA4 mutations may help us to better understand their role in ABCA4-associated retinal degenerations. PMID:26261413

  10. [Transmissing electron microscopy of the vitreo-macular border in clinically significant diabetic macular edema].

    PubMed

    Synek, S; Pác, L; Synková, M

    2007-09-01

    The authors examined samples of the epimacular tissue in clinically significant macular edema by means of the transmissing electron microscopy. They did not found morphological differences between samples from patients already treated by means of laser photocoagulation before the pars plana vitrectomy and those without the laser treatment. Findings may be divided into three groups: (1) the inner limiting membrane (ILM) covered with collagen vitreous fibers, (2) cells' elements of the fibroblasts category, and (3) fibrous astrocytes in the vitreous cortex constituting one- or multilayer cellular membranes.

  11. Monitoring pigmented skin lesions

    NASA Astrophysics Data System (ADS)

    Wallace, Vincent P.; Bamber, Jeffery C.; Ott, Robert J.; Crawford, Diane C.; Mortimer, Peter S.

    2002-06-01

    The rising incidence of skin cancer has led to an increase in the number of patients with skin lesions that require diagnosis, mostly using subjective visual examination. Successful treatment depends on early diagnosis. Unfortunately diagnostic accuracy, even by experts, can be as low as 56%; therefore, an accurate, objective diagnostic aid is greatly needed. Reflectance characteristics of pigmented skin lesions were documented to evaluate their diagnostic potential. Reflectance spectra in the wavelength range 320-1100nm were obtained from 260 lesions. Differences between spectra from benign and malignant lesions were utilized by extracting features with the best discriminating power. Discrimination was evaluated using two techniques: multivariate statistical analysis and artificial neural networks, using histology as the standard. Each technique was tested in a blind study and assessed in terms of its ability to diagnose new cases and compared to the clinical diagnosis. The artificial neural network achieved the best diagnostic performance for discriminating between malignant melanoma and benign nevi, having a sensitivity of 100% and a specificity of 65%. Utilization of visible and infrared techniques for monitoring skin lesions has lead to improvements in diagnostic accuracy. We conclude that these techniques are worthy of further development and evaluation in clinical practice as a screening tool.

  12. Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment.

    PubMed

    Mitchell, Paul; Bressler, Neil; Doan, Quan V; Dolan, Chantal; Ferreira, Alberto; Osborne, Aaron; Rochtchina, Elena; Danese, Mark; Colman, Shoshana; Wong, Tien Y

    2014-01-01

    Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%). Ranibizumab given as needed would reduce incident blindness by 68% (64-71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39%) with monthly intravitreal ranibizumab, and by 28% (23-33%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.

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

    PubMed Central

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

    2013-01-01

    Purpose 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. Methods 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. Results 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). Conclusions GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker

  14. A pigmented calcifying odontogenic cyst.

    PubMed

    Soames, J V

    1982-04-01

    A case of the pigmented variant of the calcifying odontogenic cyst occurring in a 15-year-old West Indian girl is reported. Melanin pigment was widely distributed and appeared in greatest amount in cells exhibiting the appearance of stellate reticulum. Ultrastructural examination demonstrated large numbers of melanosomes in these cells but relatively few in epithelial ghost cells. The latter contained thick bundles of tonofilaments. Melanocytes were identified and two forms were distinguished, depending on their content of premelanosomes and fully melanized melanosomes.

  15. Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Baumann, Bernhard; Götzinger, Erich; Pircher, Michael; Sattmann, Harald; Schütze, Christopher; Schlanitz, Ferdinand; Ahlers, Christian; Schmidt-Erfurth, Ursula; Hitzenberger, Christoph K.

    2010-11-01

    We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results from measurements in the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging based on the retinal features polarizing properties. Repeatability measurements were performed in retinas diagnosed with drusen and geographic atrophy in order to evaluate the performance of the described methods. PS-OCT appears as a promising imaging modality for three-dimensional retinal imaging and ranging with additional contrast based on the structures' tissue-inherent polarization properties.

  16. Glycolysis in Patients with Age-Related Macular Degeneration

    PubMed Central

    Yokosako, Kanako; Mimura, Tatsuya; Funatsu, Hideharu; Noma, Hidetaka; Goto, Mari; Kamei, Yuko; Kondo, Aki; Matsubara, Masao

    2014-01-01

    Purpose: Retinal adenosine triphosphate is mainly produced via glycolysis, so inhibition of glycolysis may promote the onset and progression of age-related macular degeneration (AMD). When glycolysis is inhibited, pyruvate is metabolized by lactic acid fermentation instead of entering the mitochondrial tricarboxylic acid (TCA) cycle. We measured urinary pyruvate and lactate levels in patients with AMD. Methods: Eight patients with typical AMD (tAMD group) and 9 patients with polypoidal choroidal vasculopathy (PCV group) were enrolled. Urinary levels of pyruvate, lactate, α-hydroxybutyrate, and β-hydroxybutyrate were measured in all patients. Results: The mean urinary levels of pyruvate and lactate were 8.0 ± 2.8 and 7.5 ± 8.3 μg/mg creatinine (reference values: 0.5-6.6 and 0.0-1.6), respectively, with the mean increase over the reference value being 83.6 ± 51.1% and 426.5 ± 527.8%, respectively. In 12 patients (70.6%), the lactate/pyruvate ratio was above the reference range. Urinary levels of α-hydroxybutyrate and β-hydroxybutyrate were decreased by -31.9 ± 15.2% and -33.1 ± 17.5% compared with the mean reference values. There were no significant differences of any of these glycolysis metabolites between the tAMD and PCV groups. Multivariate analysis revealed that none of the variables tested, including patient background factors (age, hypertension, diabetes, hyperlipidemia, cerebrovascular disease, alcohol, smoking, visual acuity, and AMD phenotype), were significantly associated with the lactate/pyruvate ratio. Conclusion: A high lactate/pyruvate ratio is a well-known marker of mitochondrial impairment, and it indicates poor oxidative function in AMD. Our results suggest that increased lactate levels may be implicated in the pathogenesis of AMD. PMID:25191529

  17. Prevalence of age-related macular degeneration among the elderly

    PubMed Central

    Rasoulinejad, Seyed Ahmad; Zarghami, Amin; Hosseini, Seyed Reza; Rajaee, Neda; Rasoulinejad, Seyed Elahe; Mikaniki, Ebrahim

    2015-01-01

    Background: Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in elderly population in the developing countries. Previous epidemiological studies revealed various potential modifiable risk factors for this disease. The purpose of this study was to evaluate the prevalence of AMD among elderly living in Babol, North of Iran. Methods: The study population of this cross-sectional study came from the Amirkola Health and Ageing Project (AHAP), the first comprehensive cohort study of the health of people aged 60 years and over in Amirkola, North of Iran. The prevalence of AMD was estimated and its risk was determined using logistic regression analysis (LRA) with regard to variables such as smoking, hyperlipidemia, hypertension and diabetes. Results: Five hundred and five participants with mean age of 71.55±5.9 (ranged 60-89) years entered the study. The prevalence of AMD was 17.6%. There was a significant association between AMD and smoking (P<0.001) but no association was seen with AMD and age, level of education, history of hyperlipidemia, hypertension and diabetes. Multiple LRAs revealed that smoking increased AMD by odds ratio of 5.03 (95% confidence interval 2.47-10.23 p<0.001) as compared to nonsmokers Conclusion: According to our findings, the prevalence of AMD was relatively high and smoking increased the risk of AMD in the elderly population. PMID:26644880

  18. Age-related macular degeneration: experimental and emerging treatments

    PubMed Central

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

    2009-01-01

    Purpose: This essay reviews the experimental treatments and new imaging modalities that are currently being explored by investigators to help treat patients with age-related macular degeneration (AMD). Design: Interpretative essay. Methods: Literature review and interpretation. Results: Experimental treatments to preserve vision in patients with exudative AMD include blocking vascular endothelial growth factor (VEGF), binding VEGF, and modulating the VEGF receptors. Investigators are also attempting to block signal transduction with receptor tyrosine kinase inhibitors. Experimental treatments for non-exudative AMD include agents that target inflammation, oxidative stress, and implement immune-modulation. The effectiveness of these newer pharmacologic agents has the potential to grow exponentially when used in combination with new and improved imaging modalities that can help identify disease earlier and follow treatment response more precisely. Conclusion: With a better understanding, at the genetic and molecular level, of AMD and the development of superior imaging modalities, investigators are able to offer treatment options that may offer unprecedented visual gains while reducing the need for repetitive treatments. PMID:19668561

  19. Yolk pigments of the Mexican leaf frog.

    PubMed

    Marinetti, G V; Bagnara, J T

    1983-02-25

    Eggs of the Mexican leaf frog contain blue and yellow pigments identified as biliverdin and lutein, respectively. Both pigments are bound to proteins that occur in crystalline form in the yolk platelet. The major blue pigment is biliverdin IX alpha. The eggs vary in color from brilliant blue to pale yellow-green depending on the amount of each pigment. These pigments may provide protective coloration to the eggs. PMID:6681678

  20. Yolk pigments of the Mexican leaf frog.

    PubMed

    Marinetti, G V; Bagnara, J T

    1983-02-25

    Eggs of the Mexican leaf frog contain blue and yellow pigments identified as biliverdin and lutein, respectively. Both pigments are bound to proteins that occur in crystalline form in the yolk platelet. The major blue pigment is biliverdin IX alpha. The eggs vary in color from brilliant blue to pale yellow-green depending on the amount of each pigment. These pigments may provide protective coloration to the eggs.

  1. Inhibitors of intracellular signaling pathways that lead to stimulated epidermal pigmentation: perspective of anti-pigmenting agents.

    PubMed

    Imokawa, Genji; Ishida, Koichi

    2014-01-01

    Few anti-pigmenting agents have been designed and developed according to their known hyperpigmentation mechanisms and corresponding intracellular signaling cascades. Most anti-pigmenting agents developed so far are mechanistically involved in the interruption of constitutional melanogenic mechanisms by which skin color is maintained at a normal and unstimulated level. Thus, owing to the difficulty of confining topical application to a specific hyperpigmented skin area, potent anti-pigmenting agents capable of attenuating the natural unstimulated pigmentation process have the risk of leading to hypopigmentation. Since intracellular signaling pathways within melanocytes do not function substantially in maintaining normal skin color and are activated only by environmental stimuli such as UV radiation, specifically down-regulating the activation of melanogenesis to the constitutive level would be an appropriate strategy to develop new potent anti-pigmenting agents with a low risk of hypopigmentation. In this article, we review the hyperpigmentation mechanisms and intracellular signaling pathways that lead to the stimulation of melanogenesis. We also discuss a screening and evaluation system to select candidates for new anti-melanogenic substances by focusing on inhibitors of endothelin-1 or stem cell factor-triggered intracellular signaling cascades. From this viewpoint, we show that extracts of the herbs Withania somnifera and Melia toosendan and the natural chemicals Withaferin A and Astaxanthin are new candidates for potent anti-pigmenting substances that avoid the risk of hypopigmentation. PMID:24823877

  2. Observational study of subclinical diabetic macular edema

    PubMed Central

    Bressler, N M; Miller, K M; Beck, R W; Bressler, S B; Glassman, A R; Kitchens, J W; Melia, M; Schlossman, D K

    2012-01-01

    Purpose To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period. Methods In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 μm on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME (performed at the discretion of the investigator). Results The cumulative probability of meeting an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years. Conclusions Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification. PMID:22441027

  3. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  4. Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory

    PubMed Central

    Baget-Bernaldiz, Marc; Pareja-Rios, Alicia; Lopez-Galvez, Maribel; Navarro-Gil, Raul; Verges, Raquel

    2016-01-01

    Diabetic macular edema (DME) can cause blindness in diabetic patients suffering from diabetic retinopathy (DR). DM parameters controls (glycemia, arterial tension, and lipids) are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF) is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug. PMID:27761468

  5. New Computer Simulations of Macular Neural Functioning

    NASA Technical Reports Server (NTRS)

    Ross, Muriel D.; Doshay, D.; Linton, S.; Parnas, B.; Montgomery, K.; Chimento, T.

    1994-01-01

    We use high performance graphics workstations and supercomputers to study the functional significance of the three-dimensional (3-D) organization of gravity sensors. These sensors have a prototypic architecture foreshadowing more complex systems. Scaled-down simulations run on a Silicon Graphics workstation and scaled-up, 3-D versions run on a Cray Y-MP supercomputer. A semi-automated method of reconstruction of neural tissue from serial sections studied in a transmission electron microscope has been developed to eliminate tedious conventional photography. The reconstructions use a mesh as a step in generating a neural surface for visualization. Two meshes are required to model calyx surfaces. The meshes are connected and the resulting prisms represent the cytoplasm and the bounding membranes. A finite volume analysis method is employed to simulate voltage changes along the calyx in response to synapse activation on the calyx or on calyceal processes. The finite volume method insures that charge is conserved at the calyx-process junction. These and other models indicate that efferent processes act as voltage followers, and that the morphology of some afferent processes affects their functioning. In a final application, morphological information is symbolically represented in three dimensions in a computer. The possible functioning of the connectivities is tested using mathematical interpretations of physiological parameters taken from the literature. Symbolic, 3-D simulations are in progress to probe the functional significance of the connectivities. This research is expected to advance computer-based studies of macular functioning and of synaptic plasticity.

  6. Mechanisms of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Fowler, Benjamin J.

    2012-01-01

    Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed. PMID:22794258

  7. Macular pseudohaemorrhage secondary to Allen Dot artefact.

    PubMed

    Michaels, Luke; Alexander, Philip; Newsom, Richard

    2015-01-01

    A 34-year-old highly myopic (-11.00 D) woman presented to eye clinic with a 3 day history of right eye paracentral blurring. Visual acuities were 6/6 bilaterally. Clinical examination was normal. Fundus photography showed the classic appearance of a macular haemorrhage. This is a recognised complication of high myopia and would have accounted for the patient's symptoms. However, further photography showed that the haemorrhage seemed to 'jump' around the fundus and was even present in the fellow eye. The apparent haemorrhage was revealed to be an imaging artefact. The 'Allen Dot' is a 6 mm black mask incorporated into retinal cameras to reduce reflection. Rarely, in highly myopic eyes, optical artefact can result. To the best of our knowledge, we are the first in the literature to report artefacts from the Allen Dot masquerading as ophthalmic disease. This case re-iterates the importance of clinical examination, especially in high myopes, given the current trend towards virtual clinics. PMID:25564595

  8. The Minnesota Grading System Using Fundus Autofluorescence of Eye Bank Eyes: A Correlation To Age-Related Macular Degeneration (An AOS Thesis)

    PubMed Central

    Olsen, Timothy W.

    2008-01-01

    Purpose To establish a grading system of eye bank eyes using fundus autofluorescence (FAF) and identify a methodology that correlates FAF to age-related macular degeneration (AMD) with clinical correlation to the Age-Related Eye Disease Study (AREDS). Methods Two hundred sixty-two eye bank eyes were evaluated using a standardized analysis of FAF. Measurements were taken with the confocal scanning laser ophthalmoscope (cSLO). First, high-resolution, digital, stereoscopic, color images were obtained and graded according to AREDS criteria. With the neurosensory retina removed, mean FAF values were obtained from cSLO images using software analysis that excludes areas of atrophy and other artifact, generating an FAF value from a grading template. Age and AMD grade were compared to FAF values. An internal fluorescence reference standard was tested. Results Standardization of the cSLO machine demonstrated that reliable data could be acquired after a 1-hour warm-up. Images obtained prior to 1 hour had falsely elevated levels of FAF. In this initial analysis, there was no statistical correlation of age to mean FAF. There was a statistically significant decrease in FAF from AREDS grade 1, 2 to 3, 4 (P < .0001). An internal fluorescent standard may serve as a quantitative reference. Conclusions The Minnesota Grading System (MGS) of FAF (MGS-FAF) establishes a standardized methodology for grading eye bank tissue to quantify FAF compounds in the retinal pigment epithelium and correlate these findings to the AREDS. Future studies could then correlate specific FAF to the aging process, histopathology AMD phenotypes, and other maculopathies, as well as to analyze the biochemistry of autofluorescent fluorophores. PMID:19277247

  9. 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.

  10. 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

  11. Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration

    PubMed Central

    Li, Wenbo; Dong, Lijie; Ma, Minwang; Hu, Bojie; Lu, Zhenyu; Liu, Xun; Liu, Juping; Li, Xiaorong

    2016-01-01

    Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1). The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity. PMID:27799741

  12. Radicicol but not geldanamycin evokes oxidative stress response and efflux protein inhibition in ARPE-19 human retinal pigment epithelial cells.

    PubMed

    Ryhänen, Tuomas; Mannermaa, Eliisa; Oksala, Niku; Viiri, Johanna; Paimela, Tuomas; Salminen, Antero; Atalay, Mustafa; Kaarniranta, Kai

    2008-04-28

    Drug delivery to retinal cells has represented a major challenge for ophthalmologists for many decades. However, drug targeting to the retina is essential in therapies against retinal diseases such as age-related macular degeneration, the most common reason of blindness in the developed countries. Retinal cells are chronically exposed to oxidative stress that contributes to cellular senescence and may cause neovascularization in the most severe age-related macular degeneration cases. Various pre- and clinical studies have revealed that heat shock protein 90 (HSP90) inhibitors, such as geldanamycin and radicicol, are promising drugs in the treatment of different malignant processes. In this study, our goal was to compare the effects of 0.1 microM, 1 microM or 5 microM geldanamycin or radicicol on the oxidative stress response, cytotoxicity, and efflux protein activity (a protein pump which removes drugs from cells) in ARPE-19 (human retinal pigment epithelial, RPE) cells. Our findings indicate that geldanamycin and radicicol increased HSP70 and HSP27 expression analyzed by western blotting. Cellular levels of protein carbonyls were increased in response to 0.1 microM (P=0.048 for 24 h, P=0.018 for 48 h) or 5 microM (P=0.030 for 24 h, P=0.046 for 48 h) radicicol but not to geldanamycin analyzed by ELISA assay. In addition, HNE-protein adducts were accumulated in the RPE cells exposed to 0.1 microM or 5 microM radicicol but not to geldanamycin analyzed by western blotting. However, MTT assay revealed that 5 microM geldanamycin reduced cellular viability 20-30% (P<0.05 for 24 h, P<0.01 for 48 h), but this was not observed at any radicicol concentration in RPE cells. Interestingly, the increased oxidative stress response was associated with efflux protein inhibition (20-30%) when the cells were exposed to 1 microM or 5 microM (P<0.05) radicicol, but not in geldanamycin-treated RPE cells. These novel findings help in understanding the influence of HSP90 inhibition and

  13. Laser therapy of pigmented lesions: pro and contra.

    PubMed

    Bukvić Mokos, Zrinka; Lipozenčić, Jasna; Ceović, Romana; Stulhofer Buzina, Daška; Kostović, Krešimir

    2010-01-01

    Although frequently performed, laser removal of pigmented lesions still contains certain controversial issues. Epidermal pigmented lesions include solar lentigines, ephelides, café au lait macules and seborrheic keratoses. Dermal lesions include melanocytic nevi, blue nevi, drug induced hyperpigmentation and nevus of Ota and Ito. Some lesions exhibit both an epidermal and dermal component like Becker's nevus, postinflammatory hyperpigmentations, melasma and nevus spilus. Due to the wide absorption spectrum of melanin (500-1100 nm), several laser systems are effective in removal of pigmented lesions. These lasers include the pigmented lesion pulsed dye laser (510 nm), the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (1064 nm), which can be frequency-doubled to produce visible green light with a wavelength of 532 nm. The results of laser therapy are usually successful. However, there are still many controversies regarding the use of lasers in treating certain pigmented lesions. Actually, the essential question in removing pigmented lesions with lasers is whether the lesion has atypical features or has a malignant potential. Dermoscopy, used as a routine first-level diagnostic technique, is helpful in most cases. If there is any doubt whether the lesion is benign, then a biopsy for histologic evaluation is obligatory.

  14. Endothelial Cells Promote Pigmentation through Endothelin Receptor B Activation.

    PubMed

    Regazzetti, Claire; De Donatis, Gian Marco; Ghorbel, Houda Hammami; Cardot-Leccia, Nathalie; Ambrosetti, Damien; Bahadoran, Philippe; Chignon-Sicard, Bérengère; Lacour, Jean-Philippe; Ballotti, Robert; Mahns, Andre; Passeron, Thierry

    2015-12-01

    Findings of increased vascularization in melasma lesions and hyperpigmentation in acquired bilateral telangiectatic macules suggested a link between pigmentation and vascularization. Using high-magnification digital epiluminescence dermatoscopy, laser confocal microscopy, and histological examination, we showed that benign vascular lesions of the skin have restricted but significant hyperpigmentation compared with the surrounding skin. We then studied the role of microvascular endothelial cells in regulating skin pigmentation using an in vitro co-culture model using endothelial cells and melanocytes. These experiments showed that endothelin 1 released by microvascular endothelial cells induces increased melanogenesis signaling, characterized by microphthalmia-associated transcription factor phosphorylation, and increased tyrosinase and dopachrome tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed the increased expression on the basal layer of the epidermis above small vessels compared with perilesional skin. Endothelin acts through the activation of endothelin receptor B and the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK)1/2, and p38, to induce melanogenesis. Finally, culturing of reconstructed skin with microvascular endothelial cells led to increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken together these results demonstrated the role of underlying microvascularization in skin pigmentation, a finding that could open new fields of research for regulating physiological pigmentation and for treating pigmentation disorders such as melasma.

  15. The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells

    PubMed Central

    Johansson, Ida; Monsen, Vivi Talstad; Pettersen, Kristine; Mildenberger, Jennifer; Misund, Kristine; Kaarniranta, Kai; Schønberg, Svanhild; Bjørkøy, Geir

    2015-01-01

    Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD. PMID:26237736

  16. Computational assessment of effective dose and patient specific doses for kilovoltage stereotactic radiosurgery of wet age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    Hanlon, Justin Mitchell

    Age-related macular degeneration (AMD) is a leading cause of vision loss and a major health problem for people over the age of 50 in industrialized nations. The current standard of care, ranibizumab, is used to help slow and in some cases stabilize the process of AMD, but requires frequent invasive injections into the eye. Interest continues for stereotactic radiosurgery (SRS), an option that provides a non-invasive treatment for the wet form of AMD, through the development of the IRay(TM) (Oraya Therapeutics, Inc., Newark, CA). The goal of this modality is to destroy choroidal neovascularization beneath the pigment epithelium via delivery of three 100 kVp photon beams entering through the sclera and overlapping on the macula delivering up to 24 Gy of therapeutic dose over a span of approximately 5 minutes. The divergent x-ray beams targeting the fovea are robotically positioned and the eye is gently immobilized by a suction-enabled contact lens. Device development requires assessment of patient effective dose, reference patient mean absorbed doses to radiosensitive tissues, and patient specific doses to the lens and optic nerve. A series of head phantoms, including both reference and patient specific, was derived from CT data and employed in conjunction with the MCNPX 2.5.0 radiation transport code to simulate treatment and evaluate absorbed doses to potential tissues-at-risk. The reference phantoms were used to evaluate effective dose and mean absorbed doses to several radiosensitive tissues. The optic nerve was modeled with changeable positions based on individual patient variability seen in a review of head CT scans gathered. Patient specific phantoms were used to determine the effect of varying anatomy and gaze. The results showed that absorbed doses to the non-targeted tissues were below the threshold levels for serious complications; specifically the development of radiogenic cataracts and radiation induced optic neuropathy (RON). The effective dose

  17. [Literature review: Diabetic macular edema. Repercussions and treatment].

    PubMed

    Carmona-Moxica, Luis Roberto; Hernández-Núñez, Fabiola

    2015-01-01

    In our country there is a report of prevalence of Diabetes Mellitus in the adult population of a 10%, occupying one of the first causes of morbidity-mortality, also visual and labor incapacity. Macular edema is the first cause of lost vision in the diabetic patient. There are classic methods to detect it, as the examination with biomicroscope, indirect ophthalmoscopy, fluorangiography (FAR), and the new and gold standard method for diagnostic and sequence examination, Ocular Coherence Tomography (OCT). With OCT had been possible the study of distinct types of macular edema, that could represent distinct clinical states, with specific treatments. The protocol of treatment of macular edema, continues changing. The traditional methods as metabolic control and fotocoagulation with Laser now have more options as intravitreal injection of triamcinolone, or antiangiogenic substances, even surgical treatment with vitrectomy. There are many prospective and randomized studies evaluating this methods, so until now is difficult to determine which treatment is the best.

  18. A Novel Source of Methylglyoxal and Glyoxal in Retina: Implications for Age-Related Macular Degeneration

    PubMed Central

    Yoon, Kee Dong; Yamamoto, Kazunori; Ueda, Keiko; Zhou, Jilin; Sparrow, Janet R.

    2012-01-01

    Aging of retinal pigment epithelial (RPE) cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD). Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC) with electrospray ionization mass spectrometry (ESI-MS) we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO) and methylglyoxal (MG), that are known to modify proteins by advanced glycation endproduct (AGE) formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA) revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye. PMID:22829938

  19. [Age-related Macular Degeneration in the Japanese].

    PubMed

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  20. [Age-related Macular Degeneration in the Japanese].

    PubMed

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  1. The effects of polymer pigmentation on fingermark development techniques.

    PubMed

    Bacon, Simon R; Ojeda, Jesus J; Downham, Rory; Sears, Vaughn G; Jones, Benjamin J

    2013-11-01

    The effectiveness of latent fingerprint development techniques is heavily influenced by the physical and chemical properties of the deposition surface. The use of powder suspensions is increasing for development of prints on a range of surfaces. We demonstrate that carbon powder suspension development on polymers is detrimentally affected by the presence of common white pigment, titanium dioxide. Scanning electron microscopy demonstrates that patches of the compound are clearly associated with increased levels of powder adhesion. Substrates with nonlocalized titanium dioxide content also exhibit increased levels of carbon powder staining on a surface-wide basis. Secondary ion mass spectrometry and complementary techniques demonstrate the importance of levels of the pigment within the top 30 nm. The association is independent of fingermark deposition and may be related to surface energy variation. The detrimental effect of the pigment is not observed with small-particle reagent (MoS2 SPR) or cyanoacrylate (superglue) fuming techniques that exploit different development mechanisms.

  2. Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration

    PubMed Central

    Kang, Eui Chun; Koh, Hyoung Jun

    2015-01-01

    Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA. PMID:26425354

  3. Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; dell'Omo, Roberto

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications. PMID:24227908

  4. UNUSUAL PRESENTATION OF GENERALIZED MACULAR AMYLOIDOSIS IN A YOUNG ADULT

    PubMed Central

    Kudur, Mohan H; B, Sathish Pai; H, Sripathi; Prabhu, Smitha

    2008-01-01

    Macular amyloidosis is a common problem seen dermatology out-patient department. Generalized macular amyloidosis presenting with a poikilodermatous appearance is rare. In our case, an 18-year-old male presented with generalized hypopigmented macules with a poikilodermatous appearance of 10-year duration. His developmental milestones were normal with negative family history of similar complaints. Histopathology of hyperpigmented lesions revealed hyperkeratosis and acanthosis of epidermis and hypopigmented lesion showing only hyperkeratosis. Both lesions were showing the deposition of amorphous, hazy material in the tips of papillary dermis with perivascular inflammatory infiltrate. Congo red staining of the amorphous material was positive for amyloid. PMID:19882037

  5. Comparison of Modified-ETDRS and Mild Macular Grid Laser Photocoagulation Strategies for Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Purpose To compare two laser photocoagulation techniques for treatment of diabetic macular edema (DME): modified-ETDRS direct/grid photocoagulation (mETDRS) and a, potentially milder, but potentially more extensive, mild macular grid (MMG) laser technique in which small mild burns are placed throughout the macula, whether or not edema is present, and microaneurysms are not treated directly. Methods 263 subjects (mean age 59 years) with previously untreated DME were randomly assigned to receive laser photocoagulation by mETDRS (N=162 eyes) or MMG (N=161 eyes) technique. Visual acuity, fundus photographs and OCT measurements were obtained at baseline and after 3.5, 8, and 12 months. Treatment was repeated if DME persisted. Main Outcome Measure Change in OCT measures at 12-months follow up. Results From baseline to 12 months, among eyes with baseline central subfield thickness ≥ 250 microns, central subfield thickening decreased by an average of 88 microns in the mETDRS group and decreased by 49 microns in the MMG group (adjusted mean difference: 33 microns, 95% confidence interval 5 to 61 microns, P=0.02). Weighted inner zone thickening by OCT decreased by 42 and 28 microns, respectively (adjusted mean difference: 14 microns, 95% confidence interval 1 to 27 microns, P=0.04), maximum retinal thickening (maximum of the central and four inner subfields) decreased by 66 and 39 microns, respectively (adjusted mean difference: 27 microns, 95% confidence interval 6 to 47 microns, P=0.01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference: 0.3 mm3, 95% confidence interval 0.02 to 0.53 mm3, P=0.03). At 12 months, the mean change in visual acuity was 0 letters in the mETDRS group and 2 letters worse in the MMG group (adjusted mean difference: 2 letters, 95% confidence interval −0.5 to 5 letters, P=0.10). Conclusions At 12 months after treatment, the MMG technique is less effective at reducing OCT measured retinal thickening than the

  6. Optimal management of idiopathic macular holes

    PubMed Central

    Madi, Haifa A; Masri, Ibrahim; Steel, David H

    2016-01-01

    This review evaluates the current surgical options for the management of idiopathic macular holes (IMHs), including vitrectomy, ocriplasmin (OCP), and expansile gas use, and discusses key background information to inform the choice of treatment. An evidence-based approach to selecting the best treatment option for the individual patient based on IMH characteristics and patient-specific factors is suggested. For holes without vitreomacular attachment (VMA), vitrectomy is the only option with three key surgical variables: whether to peel the inner limiting membrane (ILM), the type of tamponade agent to be used, and the requirement for postoperative face-down posturing. There is a general consensus that ILM peeling improves primary anatomical hole closure rate; however, in small holes (<250 µm), it is uncertain whether peeling is always required. It has been increasingly recognized that long-acting gas and face-down positioning are not always necessary in patients with small- and medium-sized holes, but large (>400 µm) and chronic holes (>1-year history) are usually treated with long-acting gas and posturing. Several studies on posturing and gas choice were carried out in combination with ILM peeling, which may also influence the gas and posturing requirement. Combined phacovitrectomy appears to offer more rapid visual recovery without affecting the long-term outcomes of vitrectomy for IMH. OCP is licensed for use in patients with small- or medium-sized holes and VMA. A greater success rate in using OCP has been reported in smaller holes, but further predictive factors for its success are needed to refine its use. It is important to counsel patients realistically regarding the rates of success with intravitreal OCP and its potential complications. Expansile gas can be considered as a further option in small holes with VMA; however, larger studies are required to provide guidance on its use. PMID:26834454

  7. Optimal management of idiopathic macular holes.

    PubMed

    Madi, Haifa A; Masri, Ibrahim; Steel, David H

    2016-01-01

    This review evaluates the current surgical options for the management of idiopathic macular holes (IMHs), including vitrectomy, ocriplasmin (OCP), and expansile gas use, and discusses key background information to inform the choice of treatment. An evidence-based approach to selecting the best treatment option for the individual patient based on IMH characteristics and patient-specific factors is suggested. For holes without vitreomacular attachment (VMA), vitrectomy is the only option with three key surgical variables: whether to peel the inner limiting membrane (ILM), the type of tamponade agent to be used, and the requirement for postoperative face-down posturing. There is a general consensus that ILM peeling improves primary anatomical hole closure rate; however, in small holes (<250 µm), it is uncertain whether peeling is always required. It has been increasingly recognized that long-acting gas and face-down positioning are not always necessary in patients with small- and medium-sized holes, but large (>400 µm) and chronic holes (>1-year history) are usually treated with long-acting gas and posturing. Several studies on posturing and gas choice were carried out in combination with ILM peeling, which may also influence the gas and posturing requirement. Combined phacovitrectomy appears to offer more rapid visual recovery without affecting the long-term outcomes of vitrectomy for IMH. OCP is licensed for use in patients with small- or medium-sized holes and VMA. A greater success rate in using OCP has been reported in smaller holes, but further predictive factors for its success are needed to refine its use. It is important to counsel patients realistically regarding the rates of success with intravitreal OCP and its potential complications. Expansile gas can be considered as a further option in small holes with VMA; however, larger studies are required to provide guidance on its use.

  8. Optical modulation of transgene expression in retinal pigment epithelium

    NASA Astrophysics Data System (ADS)

    Palanker, D.; Lavinsky, D.; Chalberg, T.; Mandel, Y.; Huie, P.; Dalal, R.; Marmor, M.

    2013-03-01

    Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a "biofactory" that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.

  9. Microprobe analysis of chlorpromazine pigmentation

    SciTech Connect

    Benning, T.L.; McCormack, K.M.; Ingram, P.; Kaplan, D.L.; Shelburne, J.D.

    1988-10-01

    We describe the histochemical, ultrastructural, and microanalytical features of a skin biopsy specimen obtained from a patient with chlorpromazine pigmentation. Golden-brown pigment granules were present in the dermis, predominantly in a perivascular arrangement. The granules stained positively with the Fontana-Masson stain for silver-reducing substances and negatively with Perl's stain for iron. Electron microscopy revealed dense inclusion bodies in dermal histiocytes, pericytes, endothelial cells, and Schwann cells, as well as lying free in the extracellular matrix. These ''chlorpromazine bodies'' were quite dense even in unosmicated, unstained ultrathin sections, indicating that the pigmentation is related, at least in part, to the inclusions. Microprobe analysis of the chlorpromazine bodies revealed a striking peak for sulfur, which strongly suggests the presence of the drug or its metabolite within these inclusions.

  10. Pigmentation in Xiphophorus: an emerging system in ecological and evolutionary genetics.

    PubMed

    Culumber, Zachary W

    2014-02-01

    The genus Xiphophorus has great potential to contribute to the study of vertebrate pigmentation and elucidating the relative influence of ecology, physiology, and behavior on evolution at the molecular level. More importantly, the association between pigmentation and a functional oncogene offers the potential to understand the evolution and maintenance of cancer-causing genetic elements. Using criteria laid out recently in the literature, I demonstrate the power of the Xiphophorus system for studying pigment evolution through integrative organismal biology. Using the most recent phylogeny, the phylogenetic distribution of several important pigmentation loci are reevaluated. I then review support for existing hypotheses of the functional importance of pigmentation. Finally, new observations and hypotheses regarding some of the characteristics of pigment patterns in natural populations and open questions and future directions in the study of the evolution of these traits are discussed.

  11. Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model.

    PubMed

    Ardeljan, Christopher P; Ardeljan, Daniel; Abu-Asab, Mones; Chan, Chi-Chao

    2014-01-01

    The etiology of Age-related Macular Degeneration (AMD) remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscope-particularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death. PMID:25580276

  12. A Method for En Face OCT Imaging of Subretinal Fluid in Age-Related Macular Degeneration.

    PubMed

    Mohammad, Fatimah; Wanek, Justin; Zelkha, Ruth; Lim, Jennifer I; Chen, Judy; Shahidi, Mahnaz

    2014-01-01

    Purpose. The purpose of the study is to report a method for en face imaging of subretinal fluid (SRF) due to age-related macular degeneration (AMD) based on spectral domain optical coherence tomography (SDOCT). Methods. High density SDOCT imaging was performed at two visits in 4 subjects with neovascular AMD and one healthy subject. En face OCT images of a retinal layer anterior to the retinal pigment epithelium were generated. Validity, repeatability, and utility of the method were established. Results. En face OCT images generated by manual and automatic segmentation were nearly indistinguishable and displayed similar regions of SRF. En face OCT images displayed uniform intensities and similar retinal vascular patterns in a healthy subject, while the size and appearance of a hypopigmented fibrotic scar in an AMD subject were similar at 2 visits. In AMD subjects, dark regions on en face OCT images corresponded to reduced or absent light reflectance due to SRF. On en face OCT images, a decrease in SRF areas with treatment was demonstrated and this corresponded with a reduction in the central subfield retinal thickness. Conclusion. En face OCT imaging is a promising tool for visualization and monitoring of SRF area due to disease progression and treatment.

  13. An exploratory study evaluating the effects of macular carotenoid supplementation in various retinal diseases

    PubMed Central

    Crosby-Nwaobi, Roxanne; Hykin, Philip; Peto, Tunde; Sivaprasad, Sobha

    2016-01-01

    Purpose The aim of this study was to assess the impact of daily oral supplementation with Macushield (10 mg/d meso-zeaxanthin, 10 mg/d lutein, and 2 mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. Methods Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6 months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute- Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. Results A statistically significant increase in the MP optical density was observed using the dual-wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P<0.05) improvements in glare sensitivity in low and medium spatial frequencies were observed at 3 months and 6 months. Ceiling effects confounded other visual function tests and quality of life changes. Conclusion Supplementation with the three carotenoids enhances certain aspects of visual performance in retinal diseases. PMID:27274188

  14. 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.

  15. Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration

    PubMed Central

    Ebrahem, Quteba; Renganathan, Kutralanathan; Sears, Jonathan; Vasanji, Amit; Gu, Xiaorong; Lu, Liang; Salomon, Robert G.; Crabb, John W.; Anand-Apte, Bela

    2006-01-01

    Choroidal neovascularization (CNV), the advanced stage of age-related macular degeneration (AMD), accounts for >80% of vision loss in AMD. Carboxyethylpyrrole (CEP) protein modifications, uniquely generated from oxidation of docosahexaenoate-containing lipids, are more abundant in Bruch’s membrane from AMD eyes. We tested the hypothesis that CEP protein adducts stimulate angiogenesis and possibly contribute to CNV in AMD. Human serum albumin (HSA) or acetyl-Gly-Lys-O-methyl ester (dipeptide) were chemically modified to yield CEP-modified HSA (CEP-HSA) or CEP-dipeptide. The in vivo angiogenic properties of CEP-HSA and CEP-dipeptide were demonstrated by using the chick chorioallantoic membrane and rat corneal micropocket assays. Low picomole amounts of CEP-HSA and CEP-dipeptide stimulated neovascularization. Monoclonal anti-CEP antibody neutralized limbal vessel growth stimulated by CEP-HSA, whereas anti-VEGF antibody was found to only partially neutralize vessel growth. Subretinal injections of CEP-modified mouse serum albumin exacerbated laser-induced CNV in mice. In vitro treatments of human retinal pigment epithelial cells with CEP-dipeptide or CEP-HSA did not induce increased VEGF secretion. Overall, these results suggest that CEP-induced angiogenesis utilizes VEGF-independent pathways and that anti-CEP therapeutic modalities might be of value in limiting CNV in AMD. PMID:16938854

  16. Recent developments in the management of dry age-related macular degeneration

    PubMed Central

    Buschini, Elisa; Fea, Antonio M; Lavia, Carlo A; Nassisi, Marco; Pignata, Giulia; Zola, Marta; Grignolo, Federico M

    2015-01-01

    Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%), dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6) are under evaluation, but the results are still uncertain. New strategies aim to 1) reduce or block drusen formation, 2) reduce or eliminate inflammation, 3) lower the accumulation of toxic by-products from the visual cycle, 4) reduce or eliminate retinal oxidative stress, 5) improve choroidal perfusion, 6) replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7) develop a target gene therapy. PMID:25878491

  17. Immune Responses in Age Related Macular Degeneration and a possible Long Term Therapeutic Strategy for Prevention

    PubMed Central

    Nussenblatt, Robert B.; Lee, Richard W.J.; Chew, Emily; Wei, Lai; Liu, Baoying; Sen, Nida; Dick, Andrew D.; Ferris, Frederick L.

    2014-01-01

    Purpose To describe the immune alterations associated with, age related macular degeneration (AMD). Based on these findings, to offer an approach to possibly prevent the expression of late disease. Design Perspective Methods Review of the existing literature dealing with epidemiology, models, and immunologic findings in patients. Results 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 occurs 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. Conclusion Immune dysregulation appears to be an underlying alteration in AMD as in other diseases thought to be degenerative and due to aging. Parainflammation and immunosensescence 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. PMID:24709810

  18. Age-related macular degeneration: a target for nanotechnology derived medicines

    PubMed Central

    Birch, David G; Liang, Fong Qi

    2007-01-01

    Despite the fact that the retina is a fairly accessible portion of the central nervous system, there are virtually no treatments for early age-related macular degeneration (AMD). AMD is a degenerative retinal disease that causes progressive loss of central vision and is the leading cause of irreversible vision loss and legal blindness in individuals over the age of 50. Both environmental and genetic components play a role in its development. AMD is a multifactorial disease with characteristics that include drusen, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), geographic atrophy and, in a subset of patients, late-stage choroidal neovascularization (CNV). Drugs that inhibit vascular endothelial growth factor (VEGF) have proven effective in treating late-stage CNV, but optimal means of drug delivery remains to be determined. Microscopic particles, whose size is on the nanometer scale, show considerable promise for drug delivery to the retina, for gene therapy, and for powering prosthetic “artificial retinas.” This article summarizes the pathophysiology of AMD stressing potential applications from nanotechnology. PMID:17722514

  19. PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration

    PubMed Central

    Choudhary, Mayur; Ding, Jin-dong; Qi, Xiaoping; Boulton, Michael E.; Yao, Pei-Li; Peters, Jeffrey M.; Malek, Goldis

    2016-01-01

    Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a nuclear receptor that regulates differentiation, inflammation, lipid metabolism, extracellular matrix remodeling, and angiogenesis in multiple tissues. These pathways are also central to the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss globally. With the goal of identifying signaling pathways that may be important in the development of AMD, we investigated the impact of PPARβ/δ activation on ocular tissues affected in the disease. PPARβ/δ is expressed and can be activated in AMD vulnerable cells, including retinal pigment epithelial (RPE) and choroidal endothelial cells. Further, PPARβ/δ knockdown modulates AMD-related pathways selectively. Specifically, genetic ablation of Pparβ/δ in aged mice resulted in exacerbation of several phenotypic features of early dry AMD, but attenuation of experimentally induced choroidal neovascular (CNV) lesions. Antagonizing PPARβ/δ in both in vitro angiogenesis assays and in the in vivo experimentally induced CNV model, inhibited angiogenesis and angiogenic pathways, while ligand activation of PPARβ/δ, in vitro, decreased RPE lipid accumulation, characteristic of dry AMD. This study demonstrates for the first time, selective regulation of a nuclear receptor in the eye and establishes that selective targeting of PPARβ/δ may be a suitable strategy for treatment of different clinical sub-types of AMD. PMID:27622388

  20. Genetic Basis of Inherited Macular Dystrophies and Implications for Stem Cell Therapy

    PubMed Central

    Mellough, Carla B; Steel, David HW; Lako, Majlinda

    2009-01-01

    Untreatable hereditary macular dystrophy (HMD) presents a major burden to society in terms of the resulting patient disability and the cost to the healthcare provision system. HMD results in central vision loss in humans sufficiently severe for blind registration, and key issues in the development of therapeutic strategies to target these conditions are greater understanding of the causes of photoreceptor loss and the development of restorative procedures. More effective and precise analytical techniques coupled to the development of transgenic models of disease have led to a prolific growth in the identification and our understanding of the genetic mutations that underly HMD. Recent successes in driving differentiation of pluripotent cells towards specific somatic lineages have led to the development of more efficient protocols that can yield enriched populations of a desired phenotype. Retinal pigmented epithelial cells and photoreceptors derived from these are some of the most promising cells that may soon be used in the treatment of specific HMD, especially since rapid developments in the field of induced pluripotency have now set the stage for the production of patient-derived stem cells that overcome the ethical and methodological issues surrounding the use of embryonic derivatives. In this review we highlight a selection of HMD which appear suitable candidates for combinatorial restorative therapy, focusing specifically on where those photoreceptor loss occurs. This technology, along with increased genetic screening, opens up an entirely new pathway to restore vision in patients affected by HMD. PMID:19551904

  1. Volcano like pattern in optical coherence tomography in chronic diabetic macular edema.

    PubMed

    Pai, Sivakami A; Hussain, Nazimul; Hebri, Sudhira P; Lootah, Afra M; Dekhain, Moza A

    2014-04-01

    In this article we herein report an interesting vitreo-macular interface abnormality associated with chronic diabetic cystoid macular edema. It is an observational case study of three diabetic patients examined in the diabetic clinic. All the patients had proliferative diabetic retinopathy with chronic macular edema. A serial cross sectional OCT examination and tracking of both the longitudinal progression of macular thickening and vitreo-macular interface revealed cystoid macular edema with a characteristic hyperreflective vitreous shadow emerging from the vitreofoveal interface. All the patients had dehiscence of inner retinal layers. This particular morphological feature at the vitreo-foveolar interface, which we name as "volcano sign", has not been described earlier. The probable mechanism of such a finding probably could be due to slow progressive leakage of chronic cytoid fluid into the vitreous with condensation of the overlying vitreous. Vitreo-macular traction followed by posterior vitreous detachment probably would have contributed to such a morphological event.

  2. Volcano like pattern in optical coherence tomography in chronic diabetic macular edema.

    PubMed

    Pai, Sivakami A; Hussain, Nazimul; Hebri, Sudhira P; Lootah, Afra M; Dekhain, Moza A

    2014-04-01

    In this article we herein report an interesting vitreo-macular interface abnormality associated with chronic diabetic cystoid macular edema. It is an observational case study of three diabetic patients examined in the diabetic clinic. All the patients had proliferative diabetic retinopathy with chronic macular edema. A serial cross sectional OCT examination and tracking of both the longitudinal progression of macular thickening and vitreo-macular interface revealed cystoid macular edema with a characteristic hyperreflective vitreous shadow emerging from the vitreofoveal interface. All the patients had dehiscence of inner retinal layers. This particular morphological feature at the vitreo-foveolar interface, which we name as "volcano sign", has not been described earlier. The probable mechanism of such a finding probably could be due to slow progressive leakage of chronic cytoid fluid into the vitreous with condensation of the overlying vitreous. Vitreo-macular traction followed by posterior vitreous detachment probably would have contributed to such a morphological event. PMID:24843311

  3. Volcano like pattern in optical coherence tomography in chronic diabetic macular edema

    PubMed Central

    Pai, Sivakami A.; Hussain, Nazimul; Hebri, Sudhira P.; Lootah, Afra M.; Dekhain, Moza A.

    2014-01-01

    In this article we herein report an interesting vitreo-macular interface abnormality associated with chronic diabetic cystoid macular edema. It is an observational case study of three diabetic patients examined in the diabetic clinic. All the patients had proliferative diabetic retinopathy with chronic macular edema. A serial cross sectional OCT examination and tracking of both the longitudinal progression of macular thickening and vitreo-macular interface revealed cystoid macular edema with a characteristic hyperreflective vitreous shadow emerging from the vitreofoveal interface. All the patients had dehiscence of inner retinal layers. This particular morphological feature at the vitreo-foveolar interface, which we name as “volcano sign”, has not been described earlier. The probable mechanism of such a finding probably could be due to slow progressive leakage of chronic cytoid fluid into the vitreous with condensation of the overlying vitreous. Vitreo-macular traction followed by posterior vitreous detachment probably would have contributed to such a morphological event. PMID:24843311

  4. Associations Between Retinal Pigment Epithelium and Drusen Volume Changes During the Lifecycle of Large Drusenoid Pigment Epithelial Detachments

    PubMed Central

    Balaratnasingam, Chandrakumar; Yannuzzi, Lawrence A.; Curcio, Christine A.; Morgan, William H.; Querques, Giuseppe; Capuano, Vittorio; Souied, Eric; Jung, Jesse; Freund, K. Bailey

    2016-01-01

    Purpose Drusenoid pigment epithelial detachments (PEDs) are a defined path to atrophy in age-related macular degeneration (AMD). We analyzed the relationships between retinal pigment epithelium (RPE) and drusen volume changes during the PED lifecycle, using spectral-domain optical coherence tomography (SD-OCT). Methods Twenty-one cases of drusenoid PED tracked using SD-OCT through periods of growth and collapse were evaluated. Volumetric calculations and piece-wise linear regression analysis were used to determine the breakpoint between growth and collapse. Spectral-domain OCT scans were independently evaluated for the appearance of intraretinal hyperreflective foci, acquired vitelliform lesions (AVLs), and disruptions to the RPE+basal lamina band. Timing of these events with respect to the breakpoint was statistically evaluated. Morphometric characteristics of drusenoid PEDs were correlated with rate of PED collapse and final visual acuity. Results Mean age of subjects was 75.3 years and mean period of follow up was 4.1 years (median 4.5 years; range, 0.6–6.6 years). The lifecycle of drusenoid PEDs was asymmetric, in that the rate of collapse (0.199 mm3/month) is significantly faster (P < 0.001) than the rate of growth (0.022 mm3/month). Appearance of intraretinal hyperreflective foci and AVLs preceded the breakpoint (both P < 0.001). The timing of disruptions to the RPE+basal lamina band did not differ from the breakpoint (P = 0.510). Maximal height, volume, and diameter of drusenoid PEDs were inversely correlated with final visual acuity (all P < 0.001) and positively correlated with the rate of PED collapse (all P < 0.001). Conclusions Spectral-domain OCT signatures, plausibly attributable to anteriorly migrated RPE and disintegration of the RPE layer, precede or occur simultaneously with changes in volume of drusenoid PED during the lifecycle of this lesion. PMID:27760262

  5. Vestibular dysfunction, altered macular structure and trait localization in A/J inbred mice.

    PubMed

    Vijayakumar, Sarath; Lever, Teresa E; Pierce, Jessica; Zhao, Xing; Bergstrom, David; Lundberg, Yunxia Wang; Jones, Timothy A; Jones, Sherri M

    2015-04-01

    A/J mice develop progressive hearing loss that begins before 1 month of age and is attributed to cochlear hair cell degeneration. Screening tests indicated that this strain also develops early onset vestibular dysfunction and has otoconial deficits. The purpose of this study was to characterize the vestibular dysfunction and macular structural pathology over the lifespan of A/J mice. Vestibular function was measured using linear vestibular evoked potentials (VsEPs). Macular structural pathology was evaluated using light microscopy, scanning electron microscopy, transmission electron microscopy, confocal microscopy and Western blotting. Individually, vestibular functional deficits in mice ranged from mild to profound. On average, A/J mice had significantly reduced vestibular sensitivity (elevated VsEP response thresholds and smaller amplitudes), whereas VsEP onset latency was prolonged compared to age-matched controls (C57BL/6). A limited age-related vestibular functional loss was also present. Structural analysis identified marked age-independent otoconial abnormalities in concert with some stereociliary bundle defects. Macular epithelia were incompletely covered by otoconial membranes with significantly reduced opacity and often contained abnormally large or giant otoconia as well as normal-appearing otoconia. Elevated expression of key otoconins (i.e., otoconin 90, otolin and keratin sulfate proteoglycan) ruled out the possibility of reduced levels contributing to otoconial dysgenesis. The phenotype of A/J was partially replicated in a consomic mouse strain (C57BL/6J-Chr 17(A/J)/NaJ), thus indicating that Chr 17(A/J) contained a trait locus for a new gene variant responsible to some extent for the A/J vestibular phenotype. Quantitative trait locus analysis identified additional epistatic influences associated with chromosomes 1, 4, 9 and X. Results indicate that the A/J phenotype represents a complex trait, and the A/J mouse strain presents a new model for the

  6. Retinal pigment epithelial cell necroptosis in response to sodium iodate

    PubMed Central

    Hanus, J; Anderson, C; Sarraf, D; Ma, J; Wang, S

    2016-01-01

    Age-related macular degeneration (AMD) is a degenerative disease of the retina and the leading cause of blindness in the elderly in developed countries. The late stage of dry AMD, or geographic atrophy (GA), is characterized by extensive retinal pigment epithelium (RPE) degeneration. The underlying molecular mechanism for RPE cell death in GA remains unclear. Our previous study has established that RPE cells die predominantly from necroptosis in response to oxidative stress in vitro. Here, we extend our study and aim to characterize the nature of RPE cell death in response to sodium iodate (NaIO3) in vitro and in a NaIO3-induced retina degeneration mouse model. We found that NaIO3 induces RPE necroptosis in vitro by using a combination of molecular hallmarks. By using TUNEL assays, active caspase-3 and HMGB1 immunostaining, we confirmed that photoreceptor cells die mainly from apoptosis and RPE cells die mainly from necroptosis in response to NaIO3 in vivo. RPE necroptosis in this model is also supported by use of the RIPK1 inhibitor, Necrostatin-1. Furthermore, using novel RIPK3-GFP transgenic mouse lines, we detected RIPK3 aggregation, a hallmark of necroptosis, in the RPE cells in vivo after NaIO3 injection. Our findings suggest the necessity of re-evaluating RPE cell death mechanism in AMD models and have the potential to influence therapeutic development for dry AMD, especially GA. PMID:27551542

  7. Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

    PubMed Central

    Alexander, P; Thomson, H A J; Luff, A J; Lotery, A J

    2015-01-01

    The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD. PMID:26043704

  8. Retinal pigment epithelium transplantation: concepts, challenges, and future prospects.

    PubMed

    Alexander, P; Thomson, H A J; Luff, A J; Lotery, A J

    2015-08-01

    The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD. PMID:26043704

  9. Effect of curcumin on aging retinal pigment epithelial cells.

    PubMed

    Zhu, Wei; Wu, Yan; Meng, Yi-Fang; Wang, Jin-Yu; Xu, Ming; Tao, Jian-Jun; Lu, Jiong

    2015-01-01

    Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population. The antioxidative effects of curcumin on aging retinal pigment epithelial (RPE) cells are still unclear. We conducted an in vitro study to investigate the effects of curcumin on aging RPE cells. A pulsed H2O2 exposure aging model was adopted. Aging RPE cells were treated with curcumin 20 µM, 40 µM, and 80 µM. Apoptosis of RPE cells was analyzed by flow cytometry. The intracellular reactive oxygen species concentration was detected using a specific probe and apoptosis-associated proteins were detected by Western blot. Expression of oxidative biomarkers, including superoxide dismutase, maleic dialdehyde, and glutathione, was detected commercially available assay kits. Compared with normal cells, lower cell viability, higher apoptosis rates, and more severe oxidation status were identified in the aging RPE cell model. Curcumin improved cell viability and decreased apoptosis and oxidative stress. Further, curcumin had a significant influence on expression of apoptosis-associated proteins and oxidative stress biomarkers. In conclusion, treatment with curcumin was able to regulate proliferation, oxidative stress, and apoptosis in aging RPE cells. Accordingly, application of curcumin may be a novel strategy to protect against age-related change in AMD.

  10. Retinal pigment epithelial cell necroptosis in response to sodium iodate.

    PubMed

    Hanus, J; Anderson, C; Sarraf, D; Ma, J; Wang, S

    2016-01-01

    Age-related macular degeneration (AMD) is a degenerative disease of the retina and the leading cause of blindness in the elderly in developed countries. The late stage of dry AMD, or geographic atrophy (GA), is characterized by extensive retinal pigment epithelium (RPE) degeneration. The underlying molecular mechanism for RPE cell death in GA remains unclear. Our previous study has established that RPE cells die predominantly from necroptosis in response to oxidative stress in vitro. Here, we extend our study and aim to characterize the nature of RPE cell death in response to sodium iodate (NaIO3) in vitro and in a NaIO3-induced retina degeneration mouse model. We found that NaIO3 induces RPE necroptosis in vitro by using a combination of molecular hallmarks. By using TUNEL assays, active caspase-3 and HMGB1 immunostaining, we confirmed that photoreceptor cells die mainly from apoptosis and RPE cells die mainly from necroptosis in response to NaIO3 in vivo. RPE necroptosis in this model is also supported by use of the RIPK1 inhibitor, Necrostatin-1. Furthermore, using novel RIPK3-GFP transgenic mouse lines, we detected RIPK3 aggregation, a hallmark of necroptosis, in the RPE cells in vivo after NaIO3 injection. Our findings suggest the necessity of re-evaluating RPE cell death mechanism in AMD models and have the potential to influence therapeutic development for dry AMD, especially GA. PMID:27551542

  11. Protocol optimization for enhanced production of pigments in Spirulina.

    PubMed

    Kumar, Devendra; Kumar, Neeraj; Pabbi, Sunil; Walia, Suresh; Dhar, Dolly Wattal

    2013-01-01

    Spirulina has attracted special attention due to its importance as human foodstuff and natural colours with specific functional properties. These functional properties have been attributed to phycobilins, carotenoids, phenolics and unsaturated fatty acids. Present study was conducted under controlled phytotron conditions to identify the efficient strains of Spirulina in terms of pigment synthesis and to optimize their enhanced production. Methodology for enhanced production was standardized by varying specific environmental parameters (light intensity, temperature, carbon dioxide concentration, pH and NaCl level). Different strains of Spirulina depicted variability and environmental parameters showed distinct influence on pigments. Growth and pigment production was recorded to be most efficient under optimized conditions of light intensity (70 μmol m(-2) s(-1)), temperature (30 °C), CO2 concentration (550 ppm and 750 ppm), pH (10.5) and NaCl level (2 g L(-1)). PMID:24764599

  12. The Experience of Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  13. Technology needs for tomorrow's treatment and diagnosis of macular diseases

    NASA Astrophysics Data System (ADS)

    Soubrane, Gisèle

    2008-02-01

    Retinal imaging is the basis of macular disease's diagnosis. Currently available technologies in clinical practice are fluorescein and indocyanin green (ICG) angiographies, in addition to optical coherence tomography (OCT), which is an in vivo "histology-like" cross-sectional images of the retina. Recent developments in the field of OCT imaging include Spectral-Domain OCT. However OCT remains a static view of the macula with no direct link with dynamic observation obtained by angiographies. Adaptative optics is an encouraging perspective for fundus analysis in the future, and could be linked to OCT or angiographies. Treatments of macular disease have exploded these past few years. Pharmacologic inhibition of angiogenesis represents a novel approach in the treatment of choroidal neovascularization in eyes with age-related macular degeneration. The major action explored is the direct inhibition of the protein VEGF with antibody-like products. New anti-VEGF drugs are in development aiming at the VEGF receptors or synthesis of VEGF. But various components of the neovascular cascade, including growth factor expression, extracellular matrix modulation, integrin inhibition represent potential targets for modulation with drugs. Intra-vitreal injections are nowadays the main route of administration for these new treatments but they are potentially responsible of side effects such as endophtalmitis. Development of other routes of treatment would require new formulation of used drugs. The improvement of retinal imaging leads to a better understanding of macular disease mechanisms and will help to develop new routes and targets of treatment.

  14. Inverted Internal Limiting Membrane Flap For Large Traumatic Macular Holes

    PubMed Central

    Abou Shousha, Mohsen Ahmed

    2016-01-01

    Abstract The aim of the study was to assess the role of inverted internal limiting membrane flap as a treatment option for large traumatic macular holes. This is a prospective noncomparative study in which 12 eyes with large traumatic macular holes (basal diameter of 1300–2800 μm) since 3 to 6 months were subjected to standard 23-gauge vitrectomy with removal of the posterior hyaloid, brilliant blue G (BBG)-assisted internal limiting membrane peeling in a circular fashion keeping it attached to the edge of the hole to create a flap. At the end of the surgery, air fluid exchange was done with inversion of the internal limiting membrane flap inside the macular hole using the soft tipped cannula and sulfur hexafluoride 20% as tamponade. The main follow-up measures are the best corrected visual acuity and the optical coherence tomography for 6 to 9 months. All the included eyes had a closed hole from the first week postoperative and along the follow-up period (6–9 months). The best corrected visual acuity improved from 20/2000 to 20/200 with a median of 20/400 preoperatively to 20/400 to 20/50 with a median of 20/100 at the end of follow-up period. Inverted internal limiting membrane flap is a good adjuvant to standard vitrectomy in the management of large traumatic macular holes that led to the 100% closure rate and improvement of best corrected visual acuity. PMID:26817894

  15. Macular infarction in a patient with Toxoplasma retinochoroditis.

    PubMed

    Kumar, Vinod; Takkar, Brijesh; Chandra, Parijat; Kumar, Atul

    2016-01-11

    Toxoplasma retinochoroditis is one of the commonest causes of infectious posterior uveitis and may lead to occlusive retinitis. We present a case of a patient with Toxoplasma retinochoroditis who developed macular infarction after initial improvement on pharmacotherapy. The potential aetiology and outcome are described.

  16. Nutritional modulation of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 wi...

  17. Retinitis pigmentosa and macular degeneration in a patient with ataxia with isolated vitamin E deficiency with a novel c.717 del C mutation in the TTPA gene.

    PubMed

    Iwasa, Kazuo; Shima, Keisuke; Komai, Kiyonobu; Nishida, Yoichiro; Yokota, Takanori; Yamada, Masahito

    2014-10-15

    Ataxia with isolated vitamin E deficiency (AVED) is a neurodegenerative disease caused by a mutation in the α-tocopherol transfer protein gene (TTPA). The clinical features of the disease resemble Friedreich's ataxia. However, AVED is associated with low plasma vitamin E levels, which results in compromised antioxidant function. Dysregulation of this lipid-soluble antioxidant vitamin plays a major role in the neurodegeneration observed in AVED. Some AVED patients experience decreased visual acuity. Retinitis pigmentosa is thought to be the main cause of this visual impairment. Although antioxidant levels are important for the prevention of macular degeneration, there have been no reports of macular degeneration in AVED. Here, we describe a patient with AVED with progressive macular degeneration, who carried a novel truncating mutation-c.717 del C (p.D239EfsX25)-in exon 5 of the TTPA gene. These findings suggest that this newly identified mutation results in severely low serum vitamin E levels, which may be associated with the development of retinitis pigmentosa and macular degeneration.

  18. Clofazimine-induced Hair Pigmentation.

    PubMed

    Philip, Mariam; Samson, Joan Felicita; Simi, Puthenveedu Salahudeen

    2012-07-01

    A 45-year-old man was treated with WHO multibacillary multidrug therapy for borderline leprosy and high dose daily Clofazimine for lepra reaction. Along with the expected side effect of skin pigmentation, the patient also noticed darkening of previously grey hair. This colour persisted eight months after completing multibacillary multidrug therapy. PMID:23180930

  19. Facultative skin pigmentation in caucasians: an objective biological indicator of lifetime exposure to ultraviolet radiation?

    PubMed

    Lock-Andersen, J; Knudstorp, N D; Wulf, H C

    1998-05-01

    To investigate age and gender trends in facultative and constitutive skin pigmentation we measured skin pigmentation non-invasively and objectively by skin reflectance spectroscopy in 653 caucasians (336 females and 317 males; mean age 38 years, range 0-85) who were not using artificial tanning devices. In all subjects, measurements were performed in the late winter and pre-spring period at five sites exposed to ultraviolet (UV) radiation: the forehead, the upper chest, the upper back and the lateral and medial aspects of the upper arm, and in UV-unexposed buttock skin. Constitutive pigmentation at the buttocks was highest in the first years of life and then decreased substantially during the first two decades of life (P < 0.01). After the age of 25 years, buttock pigmentation remained at a constant level (P = 0.20). There was no gender difference in constitutive pigmentation. Facultative skin pigmentation increased with age for all the measured sites with the highest levels found at the lateral aspect of the upper arm. Based on observations in this study we propose the idea of a 'sun exposure index' (SEI) for individuals, based on objective measurements of skin pigmentation. The SEI is calculated as the increase in facultative pigmentation above the constitutive level and is expressed as a percentage of the constitutive level. The SEI appeared to be related to cumulative lifetime UV exposure and may be used in epidemiological research as an objective estimate of UV exposure at different body sites in caucasians.

  20. STAT3 activation in circulating monocytes contributes to neovascular age-related macular degeneration

    PubMed Central

    Chen, Mei; Lechner, Judith; Zhao, Jiawu; Toth, Levente; Hogg, Ruth; Silvestri, Giuliana; Kissenpfennig, Adrien; Chakravarthy, Usha; Xu, Heping

    2016-01-01

    Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular age-related macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14+CD16-), non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre+/-:SOCS3fl/fl mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laser-induced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD. PMID:27009107

  1. Swapping one red pigment for another.

    PubMed

    Davies, Kevin M

    2015-01-01

    Betalains are bright red and yellow pigments, which are produced in only one order of plants, the Caryophyllales, and replace the more familiar anthocyanin pigments. The evolutionary origin of betalain production is a mystery, but a new study has identified the first regulator of betalain production and discovered a previously unknown link between the two pigment pathways. PMID:25547597

  2. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  3. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  4. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Pigment dispersants. 178.3725 Section 178.3725 Food... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  5. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  6. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  7. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  8. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  9. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Pigment dispersants. 178.3725 Section 178.3725... § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in food-contact materials....

  10. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  11. Early changes in gene expression induced by blue light irradiation of A2E-laden retinal pigment epithelial cells

    PubMed Central

    van der Burght, Barbro W.; Hansen, Morten; Olsen, Jørgen; Zhou, Jilin; Wu, Yalin; Nissen, Mogens H.; Sparrow, Janet R.

    2016-01-01

    Purpose Accumulation of bisretinoids as lipofuscin in retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of some blinding diseases including age-related macular degeneration (AMD). To identify genes whose expression may change under conditions of bisretinoid accumulation, we investigated the differential gene expression in RPE cells that had accumulated the lipofuscin fluorophore A2E and were exposed to blue light (430 nm). Methods A2E-laden RPE cells were exposed to blue light (A2E/430 nm) at various time intervals. Cell death was quantified using Dead Red staining, and RNA levels for the entire genome was determined using DNA microarrays (Affymetrix GeneChip Human Genome 2.0 Plus). Array results for selected genes were confirmed by real-time reverse-transcriptase polymerase chain reaction. Results Principal component analysis revealed that the A2E-laden RPE cells irradiated with blue light were clearly distinguishable from the control samples. We found differential regulation of genes belonging to the following functional groups: transcription factors, stress response, apoptosis and immune response. Among the last mentioned were downregulation of four genes that coded for proteins that have an inhibitory effect on the complement cascade: (complement factor H, complement factor H-related 1, complement factor I and vitronectin) and of two belonging to the classical pathway (complement component 1, s subcomponent and complement component 1, r subcomponent). Conclusion This study demonstrates that blue light irradiation of A2E-laden RPE cells can alter the transcription of genes belonging to different functional pathways including stress response, apoptosis and the immune response. We suggest that these molecules may be associated to the pathogenesis of AMD and can potentially serve as future therapeutic targets. PMID:23742627

  12. The genetic basis of divergent pigment patterns in juvenile threespine sticklebacks

    PubMed Central

    Greenwood, A K; Jones, F C; Chan, Y F; Brady, S D; Absher, D M; Grimwood, J; Schmutz, J; Myers, R M; Kingsley, D M; Peichel, C L

    2011-01-01

    Animal pigment patterns are important for a range of functions, including camouflage and communication. Repeating pigment patterns, such as stripes, bars and spots have been of particular interest to developmental and theoretical biologists, but the genetic basis of natural variation in such patterns is largely unexplored. In this study, we identify a difference in a periodic pigment pattern among juvenile threespine sticklebacks (Gasterosteus aculeatus) from different environments. Freshwater sticklebacks exhibit prominent vertical bars that visually break up the body shape, but sticklebacks from marine populations do not. We hypothesize that these distinct pigment patterns are tuned to provide crypsis in different habitats. This phenotypic difference is widespread and appears in most of the freshwater populations that we sampled. We used quantitative trait locus (QTL) mapping in freshwater–marine F2 hybrids to elucidate the genetic architecture underlying divergence in this pigmentation pattern. We identified two QTL that were significantly associated with variation in barring. Interestingly, these QTL were associated with two distinct aspects of the pigment pattern: melanophore number and overall pigment level. We compared the QTL locations with positions of known pigment candidate genes in the stickleback genome. We also identified two major QTL for juvenile body size, providing new insights into the genetic basis of juvenile growth rates in natural populations. In summary, although there is a growing literature describing simple genetic bases for adaptive coloration differences, this study emphasizes that pigment patterns can also possess a more complex genetic architecture. PMID:21304547

  13. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), 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). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  14. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), 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). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  15. Induced pigmentation in zooplankton: a trade-off between threats from predation and ultraviolet radiation.

    PubMed

    Hansson, L A

    2000-11-22

    Ultraviolet (UV) radiation is harmful to all life, and the ongoing depletion of the ozone layer is likely to affect interactions among both terrestrial and aquatic organisms. Some organisms have evolved adaptations to reduce radiation damage, such as the various types of protective pigmentation of freshwater zooplankton. However, strong pigmentation also increases vulnerability to visually hunting predators. Hence, where both UV radiation and predation are intense, zooplankton may be sandwiched between conflicting selective pressures: to be pigmented and to be transparent at the same time. Here, I show that the level of pigmentation in copepods is up to ten times higher in lakes without predatory fishes than where fishes are present. Moreover, animals from the same population exposed to either UV light or predator scent showed a 10% difference in pigmentation after only four days, suggesting that pigmentation is an inducible trait. Hence, individual copepods are not passive victims of selective predation or radiation damage, but adjust the level of pigmentation according to the prevailing threat. The ability to adjust pigmentation level rapidly may be especially useful in situations where risk assessment is difficult due to strong seasonal and spatial variation in risk variables, such as in Arctic regions. With progressive thinning of the ozone layer, the ability of some but not other organisms to adjust protection against UV radiation may lead to counter-intuitive, large-scale alterations in freshwater food webs.

  16. Lipofuscin and N-retinylidene-N-retinylethanolamine (A2E) accumulate in retinal pigment epithelium in absence of light exposure: their origin is 11-cis-retinal.

    PubMed

    Boyer, Nicholas P; Higbee, Daniel; Currin, Mark B; Blakeley, Lorie R; Chen, Chunhe; Ablonczy, Zsolt; Crouch, Rosalie K; Koutalos, Yiannis

    2012-06-22

    The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4(-/-) than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane.

  17. Blue light-induced inflammatory marker expression in the retinal pigment epithelium-choroid of mice and the protective effect of a yellow intraocular lens material in vivo.

    PubMed

    Narimatsu, Toshio; Negishi, Kazuno; Miyake, Seiji; Hirasawa, Manabu; Osada, Hideto; Kurihara, Toshihide; Tsubota, Kazuo; Ozawa, Yoko

    2015-03-01

    Oxidative stress in the retinal pigment epithelium (RPE) is a well-accepted pathogenic change in vision-threatening diseases such as age-related macular degeneration. One source of oxidative stress is excessive light exposure, which causes excessive activation of the visual cycle. Because short wavelength light (blue light) has more energy, it is reported to be more harmful to photoreceptor cells than the other wavelengths of light. However, the biological effect of blue light in the RPE of living animals and the protective effect of a yellow intraocular lens (IOL) material that blocks blue light is still obscure. Therefore, we compared the pathogenic effect in the RPE-choroid complexes of mice exposed to light in a box made of a clear or a yellow IOL material. We measured the level of reactive oxygen species (ROS) using 2', 7'-dichlorodihydrofluorescein diacetate, the mRNA levels of inflammatory cytokines and a macrophage marker by real-time polymerase chain reaction, and the protein level of monocyte chemotactic protein-1 (MCP-1) by ELISA. The ROS level after light exposure was suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. In parallel, all the inflammatory cytokines that we measured and a macrophage marker were also suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. Therefore, a yellow IOL material suppressed, and thus blue light exacerbated, the increase in the ROS level and inflammatory cytokine expression as well as macrophage recruitment in the RPE-choroid in vivo after light exposure.

  18. Evolution of dim-light and color vision pigments.

    PubMed

    Yokoyama, Shozo

    2008-01-01

    A striking level of diversity of visual systems in different species reflects their adaptive responses to various light environments. To study the adaptive evolution of visual systems, we need to understand how visual pigments, the light-sensitive molecules, have tuned their wavelengths of light absorption. The molecular basis of spectral tuning in visual pigments, a central unsolved problem in phototransduction, can be understood only by studying how different species have adapted to various light environments. Certain amino acid replacements at 30 residues explain some dim-light and color vision in vertebrates. To better understand the molecular and functional adaptations of visual pigments, we must identify all critical amino acid replacements that are involved in the spectral tuning and elucidate the effects of their interactions on the spectral shifts.

  19. Cost-Effectiveness of Bevacizumab and Ranibizumab for Newly Diagnosed Neovascular Macular Degeneration (An American Ophthalmological Society Thesis)

    PubMed Central

    Stein, Joshua D.; Newman-Casey, Paula Anne; Mrinalini, Tavag; Lee, Paul P.; Hutton, David W.

    2013-01-01

    Purpose: To determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections. Methods: Using a Markov model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), the Medicare Fee Schedules, and the medical literature. Results: Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242,357 per quality-adjusted life year (QALY). Monthly ranibizumab gains an additional 0.02 QALYs vs monthly bevacizumab at an incremental cost-effectiveness ratio of more than $10 million per QALY. As-needed ranibizumab was dominated by monthly bevacizumab. In sensitivity analyses assuming a willingness to pay of $100,000 per QALY, the annual risk of serious vascular events would have to be at least 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100,000 per QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by one category (eg, from 20/25–20/40 to 20/50–20/80) after 2 years but all patients receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97,340 per QALY. Conclusion: Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration. PMID:24167325

  20. Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells

    PubMed Central

    Kambhampati, Siva P.; Mishra, Manoj K.; Mastorakos, Panagiotis; Oh, Yumin; Lutty, Gerard A.; Kannan, Rangaramanujam M.

    2016-01-01

    Triamcinolone acetonide (TA) is a potent, intermediate-acting, steroid that has anti-inflammatory and anti-angiogenic activity. Intravitreal administration of TA has been used for diabetic macular edema, proliferative diabetic retinopathy and exudative age-related macular degeneration (AMD). However, the hydrophobicity, lack of solubility, and the side effects limit its effectiveness in the treatment of retinal diseases. In this study, we explore a PAMAM dendrimer-TA conjugate (D-TA) as a potential strategy to improve intracellular delivery and efficacy of TA to target cells. The conjugates were prepared with a high drug payload (~21%) and were readily soluble in saline. Compared to free TA, D-TA demonstrated a significantly improved toxicity profile in two important target [microglial and human retinal pigment epithelium (RPE)] cells. The D-TA was ~100-fold more effective than free TA in its anti-inflammatory activity (measured in microglia), and in suppressing VEGF production (in hypoxic RPE cells). Dendrimer-based delivery may improve the efficacy of TA towards both its key targets of inflammation and VEGF production, with significant clinical implications. PMID:25701805

  1. MECHANISMS FOR COUNTERING OXIDATIVE STRESS AND DAMAGE IN RETINAL PIGMENT EPITHELIUM

    PubMed Central

    Plafker, Scott M.; O’Mealey, Gary B.; Szweda, Luke I.

    2013-01-01

    Clinical and experimental evidence supports that chronic oxidative stress is a primary contributing factor to numerous retinal degenerative diseases, such as age-related macular degeneration (AMD). Eyes obtained postmortem from AMD patients have extensive free radical damage to the proteins, lipids, DNA, and mitochondria of their retinal pigment epithelial (RPE) cells. In addition, several mouse models of chronic oxidative stress develop many of the pathological hallmarks of AMD. However, the extent to which oxidative stress is an etiologic component versus its involvement in disease progression remains a major unanswered question. Further, whether the primary target of oxidative stress and damage is photoreceptors or RPE cells, or both, is still unclear. In this review, we discuss the major functions of RPE cells with an emphasis on the oxidative challenges these cells encounter and the endogenous antioxidant mechanisms employed to neutralize the deleterious effects that such stresses can elicit if left unchecked. PMID:22878106

  2. Prohibitin as the Molecular Binding Switch in the Retinal Pigment Epithelium.

    PubMed

    Sripathi, Srinivas R; Sylvester, O'Donnell; He, Weilue; Moser, Trevor; Um, Ji-Yeon; Lamoke, Folami; Ramakrishna, Wusirika; Bernstein, Paul S; Bartoli, Manuela; Jahng, Wan Jin

    2016-02-01

    Previously, our molecular binding study showed that prohibitin interacts with phospholipids, including phosphatidylinositide and cardiolipin. Under stress conditions, prohibitin interacts with cardiolipin as a retrograde response to activate mitochondrial proliferation. The lipid-binding switch mechanism of prohibitin with phosphatidylinositol-3,4,5-triphosphate and cardiolipin may suggest the role of prohibitin effects on energy metabolism and age-related diseases. The current study examined the region-specific expressions of prohibitin with respect to the retina and retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). A detailed understanding of prohibitin binding with lipids, nucleotides, and proteins shown in the current study may suggest how molecular interactions control apoptosis and how we can intervene against the apoptotic pathway in AMD. Our data imply that decreased prohibitin in the peripheral RPE is a significant step leading to mitochondrial dysfunction that may promote AMD progression. PMID:26661103

  3. Dominance and stress signalling of carotenoid pigmentation in Arctic charr (Salvelinus alpinus): lateralization effects?

    PubMed

    Backström, Tobias; Heynen, Martina; Brännäs, Eva; Nilsson, Jan; Magnhagen, Carin

    2015-01-01

    Social conflicts are usually solved by agonistic interactions where animals use cues to signal dominance or subordinance. Pigmentation change is a common cue used for signalling. In our study, the involvement of carotenoid-based pigmentation in signalling was investigated in juvenile Arctic charr (Salvelinus alpinus). Size-matched pairs were analysed for pigmentation both before and after being tested for competitive ability. We found that dominant individuals had fewer carotenoid-based spots on the right and left sides as well as lower plasma cortisol levels compared to subordinate individuals. Further, the number of spots on both sides was positively associated with plasma cortisol levels. These results indicate that carotenoid-based pigmentation in Arctic charr signals dominance and stress coping style. Further, it also appears as if carotenoid-based pigmentation is lateralized in Arctic charr, and that the right side signals aggression and dominance whereas the left side signals stress responsiveness.

  4. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration

    PubMed Central

    Jia, Yali; Bailey, Steven T.; Wilson, David J.; Tan, Ou; Klein, Michael L.; Flaxel, Christina J.; Potsaid, Benjamin; Liu, Jonathan J.; Lu, Chen D.; Kraus, Martin F.; Fujimoto, James G.; Huang, David

    2014-01-01

    Purpose To detect and quantify choroidal neovascularization (CNV) in age-related macular degeneration (AMD) patients using optical coherence tomography (OCT) angiography. Design Observational, cross-sectional study. Participants Five normal subjects and five neovascular AMD patients were included. Methods Five eyes with neovascular AMD and five normal age-matched controls were scanned by a high-speed (100,000 A-scans/sec) 1050 nm wavelength swept-source OCT. The macular angiography scan covered a 3×3 mm area and comprised 200×200×8 A-scans acquired in 3.5 sec. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by three dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2D angiograms from the 3 layers. CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. Main Outcome Measurements CNV angiogram, CNV area, and CNV flow index. Results En face OCT angiograms of CNVs showed sizes and locations that were confirmed by fluorescein angiography. OCT angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in one case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch’s layer and classify type I and type II CNV. A feeder vessel could be identified in one case. Higher flow indexes were associated with larger CNV and type II CNV. Conclusions OCT angiography provides depth

  5. Diabetic macular edema: new concepts in patho-physiology and treatment

    PubMed Central

    2014-01-01

    Diabetic macular edema (DME), a serious eye complication caused primarily by hyperglycemia, is one of the major causes of blindness. DME, which is characterized by cystic retinal thickening or lipid deposition, is prone to relapse after successful treatment. DME is a complex pathological process caused by multiple factors, including breakdown of the inner and outer blood-retinal barriers, oxidative stress, and elevated levels of vascular endothelial growth factor which have been demonstrated in both preclinical and clinical studies. Starling’s law theory explains many of the features of DME. Early detection and treatment of DME can prevent vision loss. Current effective interventions for DME include treatment of systemic risk factors, such as elevated blood glucose, blood pressure and dyslipidemia. Ophthalmic treatments include laser photocoagulation, surgery and intraocular pharmacotherapy. New drugs, which are given by intraocular injection, have emerged in recent years to become first line treatment for DME that affects the central macula with loss of vision. Laser photocoagulation is still the gold standard of treatment for DME which does not involve the central macular. This review outlines these new treatments with particular emphasis on the optimal timing of how they are given. PMID:24955234

  6. Availability and Utilization of Pigments from Microalgae.

    PubMed

    Begum, Hasina; Yusoff, Fatimah Md; Banerjee, Sanjoy; Khatoon, Helena; Shariff, Mohamed

    2016-10-01

    Microalgae are the major photosynthesizers on earth and produce important pigments that include chlorophyll a, b and c, β-carotene, astaxanthin, xanthophylls, and phycobiliproteins. Presently, synthetic colorants are used in food, cosmetic, nutraceutical, and pharmaceutical industries. However, due to problems associated with the harmful effects of synthetic colorants, exploitation of microalgal pigments as a source of natural colors becomes an attractive option. There are various factors such as nutrient availability, salinity, pH, temperature, light wavelength, and light intensity that affect pigment production in microalgae. This paper reviews the availability and characteristics of microalgal pigments, factors affecting pigment production, and the application of pigments produced from microalgae. The potential of microalgal pigments as a source of natural colors is enormous as an alternative to synthetic coloring agents, which has limited applications due to regulatory practice for health reasons.

  7. Availability and Utilization of Pigments from Microalgae.

    PubMed

    Begum, Hasina; Yusoff, Fatimah Md; Banerjee, Sanjoy; Khatoon, Helena; Shariff, Mohamed

    2016-10-01

    Microalgae are the major photosynthesizers on earth and produce important pigments that include chlorophyll a, b and c, β-carotene, astaxanthin, xanthophylls, and phycobiliproteins. Presently, synthetic colorants are used in food, cosmetic, nutraceutical, and pharmaceutical industries. However, due to problems associated with the harmful effects of synthetic colorants, exploitation of microalgal pigments as a source of natural colors becomes an attractive option. There are various factors such as nutrient availability, salinity, pH, temperature, light wavelength, and light intensity that affect pigment production in microalgae. This paper reviews the availability and characteristics of microalgal pigments, factors affecting pigment production, and the application of pigments produced from microalgae. The potential of microalgal pigments as a source of natural colors is enormous as an alternative to synthetic coloring agents, which has limited applications due to regulatory practice for health reasons. PMID:25674822

  8. Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction

    PubMed Central

    Liu, Zhongbo; Sun, Lijuan; Zhu, Lu; Jia, Xu; Li, Xuesen; Jia, Haiqun; Wang, Ying; Weber, Peter; Long, Jiangang; Liu, Jiankang

    2008-01-01

    Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo, at 75 µmol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochon-drial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre-treatment with HTS dose dependently and also time dependently protected the ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction. A short-term pre-treatment with HTS (48 h) required >75 µmol/L for showing protection while a long-term pre-treatment (7 days) showed protective effect from 5 µmol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria-targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial-targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke-induced or age-related retinal pigment epithelial degeneration, such as age-associated macular degeneration. PMID:20938484

  9. Macular Structure and Function in Nonhuman Primate Experimental Glaucoma

    PubMed Central

    Wilsey, Laura J.; Reynaud, Juan; Cull, Grant; Burgoyne, Claude F.; Fortune, Brad

    2016-01-01

    Purpose To evaluate structure and function of macular retinal layers in nonhuman primate (NHP) experimental glaucoma (EG). Methods Twenty-one NHP had longitudinal imaging of macular structure by SDOCT, 16 also had recordings of function by multifocal ERG. The average thickness over 15° was derived for seven individual SDOCT layers: macular nerve fiber layer (m-NFL), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer+inner segments combined (ONL+IS), and outer segments (OS). Peripapillary RNFL thickness (ppRNFLT) was measured from a single circular B-scan with 12° diameter. Responses to a slow-sequence multifocal ERG (mfERG) stimulus (7F) were filtered (at 75 Hz) into low- and high-frequency components (LFC, HFC). Results At final follow-up, significant structural loss occurred only in EG eyes and only for ppRNFLT (−29 ± 23%), m-NFL (−17 ± 16%), RGCL (−22 ± 15%), and IPL (−19 ± 14%); though there was also a small increase in OPL (+6 ± 7%) and ONL+IS (4 ± 4%) and a similar tendency for INL. Macular structural loss was correlated with ppRNFLT only for the NFL, RGCL and IPL (R = 0.95, 0.93 and 0.95, respectively, P < 0.0001). Significant functional loss occurred only for HFC and N2 in EG eyes. Significant longitudinal structure–function correlations (P < 0.01) were observed only in EG eyes and only for mfERG HFC and N2: HFC was correlated with ppRNFLT (R = 0.69), macular NFL (R = 0.67), RGCL (R = 0.74), and IPL (R = 0.72); N2 was correlated with RGCL (R = 0.54) and IPL (R = 0.48). High-frequency components amplitude change was inversely correlated with outer retinal thickness change (= −0.66). Conclusions Macular structural and functional losses are correlated and specific to ganglion cells over a wide range of EG severity. Outer retinal changes are likely due to inner retinal loss. PMID:27082305

  10. Early imaging of a macular hole following vitrectomy with primary silicone oil tamponade

    PubMed Central

    Saha, Niladri; Lake, Stewart; Wang, Bob Z

    2011-01-01

    Background To describe the morphology of a macular hole in the early postoperative period following vitrectomy with primary silicone oil tamponade. Methods A case report with optical coherence tomography (OCT) scans prior to surgery, at 20 minutes postoperatively and then at 17 hours postoperatively. Results OCT images of a 73-year-old woman with a stage 3 macular hole were obtained. At 20 minutes postoperatively, there was a reduction in intraretinal cysts and a reduction in macular hole size with elevated-open configuration. At 17 hours postoperatively, complete macular hole closure was noted. Conclusion OCT Images of a macular hole in the early postoperative period have been successfully obtained. Macular holes can close within 24 hours postoperatively and show morphological changes that may be predictive of closure within 20 minutes postoperatively. PMID:22140310

  11. Holographic films from carotenoid pigments

    NASA Astrophysics Data System (ADS)

    Toxqui-López, S.; Lecona-Sánchez, J. F.; Santacruz-Vázquez, C.; Olivares-Pérez, A.; Fuentes-Tapia, I.

    2014-02-01

    Carotenoids pigments presents in pineapple can be more than just natural dyes, which is one of the applications that now at day gives the chemical industry. In this research shown that can be used in implementing of holographic recording Films. Therefore we describe the technique how to obtain this kind of pigments trough spay drying of natural pineapple juice, which are then dissolved with water in a proportion of 0.1g to 1mL. The obtained sample is poured into glass substrates using the gravity method, after a drying of 24 hours in laboratory normal conditions the films are ready. The films are characterized by recording transmission holographic gratings (LSR 445 NL 445 nm) and measuring the diffraction efficiency holographic parameter. This recording material has good diffraction efficiency and environmental stability.

  12. Cutaneous metastatic pigmented breast carcinoma.

    PubMed

    Gaitan-Gaona, Francisco; Said, Mirra C; Valdes-Rodriguez, Rodrigo

    2016-01-01

    A 66-year-old woman presented with a 3 cm black, ulcerated nodule located on the skin of the upper abdomen, just below the breast. The lesion was painful to the touch, but the patient reported no other associated symptoms and was otherwise healthy. A 4-mm punch biopsy of the affected skin was obtained and the histological diagnosis was cutaneous metastatic pigmented breast carcinoma. PMID:27136637

  13. New group of ceramic pigments

    SciTech Connect

    Cherepanov, E.S.; Grum-Grzhimailo, O.S.; Belostotskaya, N.S.; Bibilashvili, M.S.

    1987-03-01

    The authors assess the corrosion resistance, crystal structure, chemical composition and color properties of a variety of zircon-based materials used as pigments and protective coatings for ceramic tiles. The constituents of these materials include, apart from zircon, iron oxides, vanadium oxides, and the sulfides, selenides and tellurides of cadmium. The effects of these constituents on the structural behavior of the zirconium silicate are investigated.

  14. Human skin pigmentation as an adaptation to UV radiation

    PubMed Central

    Jablonski, Nina G.; Chaplin, George

    2010-01-01

    Human skin pigmentation is the product of two clines produced by natural selection to adjust levels of constitutive pigmentation to levels of UV radiation (UVR). One cline was generated by high UVR near the equator and led to the evolution of dark, photoprotective, eumelanin-rich pigmentation. The other was produced by the requirement for UVB photons to sustain cutaneous photosynthesis of vitamin D3 in low-UVB environments, and resulted in the evolution of depigmented skin. As hominins dispersed outside of the tropics, they experienced different intensities and seasonal mixtures of UVA and UVB. Extreme UVA throughout the year and two equinoctial peaks of UVB prevail within the tropics. Under these conditions, the primary selective pressure was to protect folate by maintaining dark pigmentation. Photolysis of folate and its main serum form of 5-methylhydrofolate is caused by UVR and by reactive oxygen species generated by UVA. Competition for folate between the needs for cell division, DNA repair, and melanogenesis is severe under stressful, high-UVR conditions and is exacerbated by dietary insufficiency. Outside of tropical latitudes, UVB levels are generally low and peak only once during the year. The populations exhibiting maximally depigmented skin are those inhabiting environments with the lowest annual and summer peak levels of UVB. Development of facultative pigmentation (tanning) was important to populations settling between roughly 23° and 46° , where levels of UVB varied strongly according to season. Depigmented and tannable skin evolved numerous times in hominin evolution via independent genetic pathways under positive selection. PMID:20445093

  15. Effects of blue light on pigment biosynthesis of Monascus.

    PubMed

    Chen, Di; Xue, Chunmao; Chen, Mianhua; Wu, Shufen; Li, Zhenjing; Wang, Changlu

    2016-04-01

    The influence of different illumination levels of blue light on the growth and intracellular pigment yields of Monascus strain M9 was investigated. Compared with darkness, constant exposure to blue light of 100 lux reduced the yields of six pigments, namely, rubropunctatamine (RUM), monascorubramine (MOM), rubropunctatin (RUN), monascorubrin (MON), monascin (MS), and ankaflavin (AK). However, exposure to varying levels of blue light had different effects on pigment production. Exposure to 100 lux of blue light once for 30 min/day and to 100 lux of blue light once and twice for 15 min/day could enhance RUM, MOM, MS, and AK production and reduce RUN and MON compared with non-exposure. Exposure to 100 lux twice for 30 min/day and to 200 lux once for 45 min/day decreased the RUM, MOM, MS, and AK yields and increased the RUN and MON. Meanwhile, the expression levels of pigment biosynthetic genes were analyzed by real-time quantitative PCR. Results indicated that gene MpPKS5, mppR1, mppA, mppB, mmpC, mppD, MpFasA, MpFasB, and mppF were positively correlated with the yields of RUN and MON, whereas mppE and mppR2 were associated with RUM, MOM, MS, and AK production. PMID:27033206

  16. Effects of blue light on pigment biosynthesis of Monascus.

    PubMed

    Chen, Di; Xue, Chunmao; Chen, Mianhua; Wu, Shufen; Li, Zhenjing; Wang, Changlu

    2016-04-01

    The influence of different illumination levels of blue light on the growth and intracellular pigment yields of Monascus strain M9 was investigated. Compared with darkness, constant exposure to blue light of 100 lux reduced the yields of six pigments, namely, rubropunctatamine (RUM), monascorubramine (MOM), rubropunctatin (RUN), monascorubrin (MON), monascin (MS), and ankaflavin (AK). However, exposure to varying levels of blue light had different effects on pigment production. Exposure to 100 lux of blue light once for 30 min/day and to 100 lux of blue light once and twice for 15 min/day could enhance RUM, MOM, MS, and AK production and reduce RUN and MON compared with non-exposure. Exposure to 100 lux twice for 30 min/day and to 200 lux once for 45 min/day decreased the RUM, MOM, MS, and AK yields and increased the RUN and MON. Meanwhile, the expression levels of pigment biosynthetic genes were analyzed by real-time quantitative PCR. Results indicated that gene MpPKS5, mppR1, mppA, mppB, mmpC, mppD, MpFasA, MpFasB, and mppF were positively correlated with the yields of RUN and MON, whereas mppE and mppR2 were associated with RUM, MOM, MS, and AK production.

  17. Computer-assisted three-dimensional reconstruction and simulations of vestibular macular neural connectivities

    NASA Technical Reports Server (NTRS)

    Ross, Muriel D.; Chimento, Thomas; Doshay, David; Cheng, Rei

    1992-01-01

    Results of computer-assisted research concerned with the three-dimensional reconstruction and simulations of vestibular macular neural connectivities are summarized. The discussion focuses on terminal/receptive fields, the question of synapses across the striola, endoplasmic reticulum and its potential role in macular information processing, and the inner epithelial plexus. Also included are preliminary results of computer simulations of nerve fiber collateral functioning, an essential step toward the three-dimensional simulation of a functioning macular neural network.

  18. Tryptophan in human hair: correlation with pigmentation.

    PubMed

    Bertazzo, A; Biasiolo, M; Costa, C V; Cardin de Stefani, E; Allegri, G

    2000-08-01

    The distribution of tryptophan content in human hair of various colours was evaluated, in order to study the accumulation of this amino acid, precursor of serotonin, melatonin and niacin, in hair and the influence on hair pigmentation. Pigmentation is an important factor in determining drug incorporation into hair. Results from 1211 samples of hair from healthy subjects (577 men and 634 women) show that tryptophan levels are significantly higher in males (37.83 +/- 3.45 microg/g dry hair) than in females (26.62 +/- 2.40 microg/g hair). Besides sex, age also influences the distribution of tryptophan in human hair, the highest levels being found in both sexes in the first few years of life, probably due to the influence of milk, and in aging subjects in the groups of 61-80 and > 80 years. In order to investigate the influence of hair colour, hair samples were subdivided according to colour into blond, dark blond, red, light brown, brown, black, grey and white. The hair contents of tryptophan in both sexes was higher in brown and black hair than in blond hair, but in grey and white hair concentrations were the highest, demonstrating that tryptophan accumulates among hair fibres with age. Grouping subjects by age in relation to hair colour, we observed that at ages 1-5 and 6-12 years, colour did not influence tryptophan contents, but at ages 13-19 and 20-40 years tryptophan content increased significantly from blond to brown at 13-19 years and from blond to black at 20-40 years in both sexes. Therefore, variations in tryptophan levels of human hair appear to be correlated with differences in hair colour in both sexes. Tryptophan also accumulates in hair during keratinization, as shown by the presence of high levels of this amino acid in grey and white hair. PMID:11132729

  19. Macular sub-layer thinning and association with pulmonary function tests in Amyotrophic Lateral Sclerosis.

    PubMed

    Simonett, Joseph M; Huang, Russell; Siddique, Nailah; Farsiu, Sina; Siddique, Teepu; Volpe, Nicholas J; Fawzi, Amani A

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder that may have anterior visual pathway involvement. In this study, we compare the macular structure of patients with ALS to healthy controls, and examine correlations between macular sub-layer thickness measurements and pulmonary function tests and disease duration. ALS patients underwent optical coherence tomography (OCT) imaging to obtain macular cube scans of the right eye. Macular cube OCT data from age-matched healthy subjects were provided by the OCT reading center. Semi-automated retinal segmentation software was used to quantify macular sub-layers. Pulmonary function tests and time since symptom onset were collected retrospectively from the electronic medical records of ALS patients. Macular retinal nerve fiber layer was significantly thinner in ALS patients compared to healthy controls (P < 0.05). Total macular and other sub-layer thicknesses were not reduced in the ALS cohort. Macular retinal nerve fiber layer thickness positively correlated with forced vital capacity % predicted and forced expiratory volume in 1 second % predicted (P < 0.05). In conclusion, analysis of OCT measurements supports the involvement of the anterior visual pathway in ALS. Subtle structural thinning in the macular retinal nerve fiber layer correlates with pulmonary function tests. PMID:27383525

  20. Prediction of spontaneous closure of traumatic macular hole with spectral domain optical coherence tomography

    PubMed Central

    Chen, Haoyu; Chen, Weiqi; Zheng, Kangken; Peng, Kun; Xia, Honghe; Zhu, Lei

    2015-01-01

    It has been known that some traumatic macular holes can close spontaneously. However, knowledge about the types of macular hole that can close spontaneously is limited. In this retrospective study, we investigated patients with traumatic macular hole who were followed-up for at least 6 months without any surgical intervention. Clinical data and spectral domain optical coherence tomography (SD-OCT) images were compared between groups with and without macular hole closure. Overall, 27 eyes were included. Spontaneous closure of macular hole was observed in 10 (37.0%) eyes. The holes with spontaneous closure had smaller minimum diameter (244.9 ± 114.4 vs. 523.9 ± 320.0 μm, p = 0.007) and less intraretinal cysts (10% vs. 76.5%, p = 0.001) compared to the holes that did not close spontaneously. The area under the curve of receiver operative characteristic was 0.812 and 0.832 for minimum diameter of macular hole and presence of intraretinal cysts respectively. Multivariate logistic regression showed that the presence of intraretinal cysts was an independent predictive factor for closure of macular holes. The group with spontaneous macular hole closure had a high chance of visual improvement. Our study suggests that the absence of intraretinal cysts on SD-OCT can predict spontaneous closure of traumatic macular hole. PMID:26196460

  1. Macular sub-layer thinning and association with pulmonary function tests in Amyotrophic Lateral Sclerosis

    PubMed Central

    Simonett, Joseph M.; Huang, Russell; Siddique, Nailah; Farsiu, Sina; Siddique, Teepu; Volpe, Nicholas J.; Fawzi, Amani A.

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder that may have anterior visual pathway involvement. In this study, we compare the macular structure of patients with ALS to healthy controls, and examine correlations between macular sub-layer thickness measurements and pulmonary function tests and disease duration. ALS patients underwent optical coherence tomography (OCT) imaging to obtain macular cube scans of the right eye. Macular cube OCT data from age-matched healthy subjects were provided by the OCT reading center. Semi-automated retinal segmentation software was used to quantify macular sub-layers. Pulmonary function tests and time since symptom onset were collected retrospectively from the electronic medical records of ALS patients. Macular retinal nerve fiber layer was significantly thinner in ALS patients compared to healthy controls (P < 0.05). Total macular and other sub-layer thicknesses were not reduced in the ALS cohort. Macular retinal nerve fiber layer thickness positively correlated with forced vital capacity % predicted and forced expiratory volume in 1 second % predicted (P < 0.05). In conclusion, analysis of OCT measurements supports the involvement of the anterior visual pathway in ALS. Subtle structural thinning in the macular retinal nerve fiber layer correlates with pulmonary function tests. PMID:27383525

  2. Vitrectomy for bilateral macular schisis without apparent optic disc anomalies

    PubMed Central

    Andonegui, José; Maya, José Ramón; Echeverría, Marta; Alcaine, Araceli

    2016-01-01

    A 78-year-old man complained of bilateral visual acuity loss. Optical coherence tomography examination showed bilateral macular schisis with fluid accumulation in the external retinal layers without vitreous traction. Fundus examination and fluorescein angiography were normal in both eyes. Both eyes were treated by phacoemulsification, intraocular lens implantation, and vitrectomy without laser, gas exchange, or retinal fenestration. Slow and progressive fluid resorption and improvement in VA were observed in both eyes. Macular schisis similar to the one associated with optic disc anomalies is a possibility in patients without apparent disc anomalies. Vitrectomy without laser, gas, or retinal fenestration may be a good therapeutic option even in patients with a PVD preoperatively. PMID:27703873

  3. The genetics of age-related macular degeneration.

    PubMed

    Gorin, M B; Breitner, J C; De Jong, P T; Hageman, G S; Klaver, C C; Kuehn, M H; Seddon, J M

    1999-11-01

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  4. Prediction of visual acuity recovery in cystoid macular edema.

    PubMed

    McDonnell, P J; Ryan, S J; Walonker, A F; Miller-Scholte, A

    1992-05-01

    Three consecutive patients participated in a prospective evaluation of pseudophakic cystoid macular edema. The duration of the macular edema ranged from 6 to 8 months. On the initial visit, the best corrected acuity with spectacles was determined and a potential acuity meter reading was obtained; this test suggested potential for visual recovery in two of the three patients. Sub-tenon's injections of methylprednisolone acetate (20 mg) were administered along with topical 1% prednisolone acetate and 1% atropine. One month later, visual acuity was improved by more than 2 Snellen lines in all three of the patients. A visual acuity measurement with the potential acuity meter that is better than the best corrected acuity with spectacles may reflect the presence of intact, but dysfunctional photoreceptors that are capable of restoring visual acuity upon resolution of the edema.

  5. Mutations in IMPG1 Cause Vitelliform Macular Dystrophies

    PubMed Central

    Manes, Gaël; Meunier, Isabelle; Avila-Fernández, Almudena; Banfi, Sandro; Le Meur, Guylène; Zanlonghi, Xavier; Corton, Marta; Simonelli, Francesca; Brabet, Philippe; Labesse, Gilles; Audo, Isabelle; Mohand-Said, Saddek; Zeitz, Christina; Sahel, José-Alain; Weber, Michel; Dollfus, Hélène; Dhaenens, Claire-Marie; Allorge, Delphine; De Baere, Elfride; Koenekoop, Robert K.; Kohl, Susanne; Cremers, Frans P.M.; Hollyfield, Joe G.; Sénéchal, Audrey; Hebrard, Maxime; Bocquet, Béatrice; Ayuso García, Carmen; Hamel, Christian P.

    2013-01-01

    Vitelliform macular dystrophies (VMD) are inherited retinal dystrophies characterized by yellow, round deposits visible upon fundus examination and encountered in individuals with juvenile Best macular dystrophy (BMD) or adult-onset vitelliform macular dystrophy (AVMD). Although many BMD and some AVMD cases harbor mutations in BEST1 or PRPH2, the underlying genetic cause remains unknown for many affected individuals. In a large family with autosomal-dominant VMD, gene mapping and whole-exome sequencing led to the identification of a c.713T>G (p.Leu238Arg) IMPG1 mutation, which was subsequently found in two other families with autosomal-dominant VMD and the same phenotype. IMPG1 encodes the SPACR protein, a component of the rod and cone photoreceptor extracellular matrix domains. Structural modeling indicates that the p.Leu238Arg substitution destabilizes the conserved SEA1 domain of SPACR. Screening of 144 probands who had various forms of macular dystrophy revealed three other IMPG1 mutations. Two individuals from one family affected by autosomal-recessive VMD were homozygous for the splice-site mutation c.807+1G>T, and two from another family were compound heterozygous for the mutations c.461T>C (p.Leu154Pro) and c.1519C>T (p.Arg507∗). Most cases had a normal or moderately decreased electrooculogram Arden ratio. We conclude that IMPG1 mutations cause both autosomal-dominant and -recessive forms of VMD, thus indicating that impairment of the interphotoreceptor matrix might be a general cause of VMD. PMID:23993198

  6. Geriatric vision loss due to cataracts, macular degeneration, and glaucoma.

    PubMed

    Eichenbaum, Joseph W

    2012-01-01

    The major causes of impaired vision in the elderly population of the United States are cataracts, macular degeneration, and open-angle glaucoma. Cataracts and macular degeneration usually reduce central vision, especially reading and near activities, whereas chronic glaucoma characteristically attacks peripheral vision in a silent way, impacting balance, walking, and driving. Untreated, these visual problems lead to issues with regard to taking medications, keeping track of finances and personal information, walking, watching television, and attending the theater, and often create social isolation. Thus, visually impaired individuals enter nursing homes 3 years earlier, have twice the risk of falling, and have 4× the risk of hip fracture. Consequently, many elderly with low vision exercise greater demands on community services. With the prospect of little improvement and sustained visual loss, in the face of poor tolerance of low-vision services and not accepting magnification as the only way to read, clinical depression is common. In many instances, however, early and accurate diagnosis can result in timely treatment and can preserve quality of life. This review will look at current diagnostic and therapeutic considerations. Currently, about 20.5 million people in the United States have cataracts. The number will reach 30 million by 2020. About 1.75 million Americans currently have some form of macular degeneration, and the number is estimated to increase to 2.95 million in 2020. Approximately 2.2 million Americans have glaucoma, and by 2020 that number is estimated to be close to 3.4 million people. It is projected that by 2030 there will be 72.1 million seniors. With some overlap of the above 3 groups conservatively estimated (if you add the 2030 cataract group to the macular degeneration and glaucoma groups), then about 1 in 2 senior individuals by 2030 may have some significant ocular disease, which could account for about 50% of the healthcare budget for the

  7. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  8. Grid photocoagulation improves reading ability in diffuse diabetic macular oedema.

    PubMed

    McNaught, E I; Foulds, W S; Allan, D

    1988-01-01

    Forty-eight patients with diffuse diabetic macular oedema were treated with perifoveal blue/green Argon 'grid' laser photocoagulation. Clinical assessment of patients was supported by serial fluorescein angiography. Patients were followed up for one year after treatment, and a two year follow-up was obtained in 29 patients. Statistical analysis showed no significant improvement in distance acuity, but demonstrated clear benefit as regards reading ability.

  9. Dark adaptation and the acuity/luminance response in senile macular degeneration (SMD).

    PubMed

    Brown, B; Kitchin, J L

    1983-08-01

    Patients with senile macular degeneration (SMD) often complain of problems with adaptation and have best acuity under a restricted range of lighting conditions. We investigated dark adaptation and acuity over a wide range of luminances in eight SMD patients and six age-matched controls. Some patients showed evidence of altered dark adaptation, with a much longer time required to reach asymptotic sensitivity levels than shown by normals; others had difficulty with spatial resolution at different light levels. There was good correlation between symptoms and test findings; all but one patient who reported difficulties with adaptation demonstrated either retarded adaptation, aberrant acuity/luminance response, or both. These data provide evidence that the processes which adjust the sensitivity of the retina and the spatial summation properties of the retina are disrupted in SMD.

  10. Functionalization of linen/cotton pigment prints using inorganic nano structure materials.

    PubMed

    Ibahim, N A; Eid, B M; Abd El-Aziz, E; Abou Elmaaty, T M

    2013-09-12

    The present work opens up a novel strategy for the development of new multifunctional cellulosic pigment prints. The developed process aims at modifying the solvent-free pigment printing formulations via inclusion of certain inorganic nano materials namely silver (Ag-NPs), zinc oxide (ZnO-NPs), zirconium oxide (ZrO₂-NPs) or titanium dioxide (TiO₂-NPs) at 20 g/kg paste followed by screen printing and microwave fixation. The imparted functional properties together with the depth of the obtained prints are governed by the type of nano additives, type of binder and the pigment colorant. The imparted antibacterial and/or UV protection properties to the pigment prints were retained with an acceptable level (>70%) of durability even after 20 washing cycles. The presence of nano materials on the surface of the obtained pigment prints was confirmed using SEM images and EDX spectra.

  11. Optimizing conditions for the extraction of pigments in cochineals (Dactylopius coccus Costa) using response surface methodology.

    PubMed

    González, Mónica; Méndez, Jesús; Carnero, Aurelio; Lobo, M Gloria; Afonso, Ana

    2002-11-20

    A simple method was developed for the extraction and determination of color pigments in cochineals (Dactylopius coccus Costa). The procedure was based on the solvent extraction of pigments in insect samples using methanol:water (65:35, v:v) as extractant. Two-level factorial design was used in order to optimize the solvent extraction parameters: temperature, time, methanol concentration in the extractant mixture, and the number of extractions. The results suggest that the number of extractions is statistically the most significant factor. The separation and determination of the pigments was carried out by high-performance liquid chromatography with UV-visible detection. Because the absorption spectra of different pigments are different in the visible region, it is convenient to use a diode array detector to obtain chromatographic profiles that allow for the characterization of the extracted pigments. PMID:12428945

  12. Macular oedema due to letrozole: a first case report.

    PubMed

    Moschos, Marilita M; Chatziralli, Irini P; Zagouri, Flora; Zografos, George C

    2012-11-01

    A 72-year-old woman presented with unexplained, progressive, painless visual loss in the right eye during the past six months. At presentation visual acuity (VA) was 3/60 in the right eye and 6/6 in the left eye. Anterior segment examination and intraocular pressures were normal. Dilated fundoscopy revealed significant macular oedema in the right eye and a normal fundus appearance in the left eye. Her medical history was noteworthy for breast ductal carcinoma in situ, for which she had undergone right mastectomy three years earlier. She had not received chemotherapy or radiotherapy but she had been under treatment with letrozole 2.5 mg/day over the past three years. She did not receive any other medication. Optical coherence tomography showed intraretinal fluid and a significant increase in retinal thickness in the foveal and parafoveal areas, while fluorescein angiography detected foveal hyperfluorescence and leakage of the dye in the late phase. Multifocal electroretinogram showed a decreased response in both eyes. In suspicion of letrozole-related retinopathy, the patient was advised to stop the medication. The patient agreed to receive an intravitreal injection of 0.05 ml/0.5 mg ranibizumab. One month later, VA in the right eye was 6/9 and macular oedema had apparently improved. This is the first reported case of letrozole-associated macular oedema treated with intravitreal ranibizumab.

  13. Multifocal electroretinography in patients with Stargardt's macular dystrophy

    PubMed Central

    Kretschmann, U; Seeliger, M; Ruether, K; Usui, T; Apfelstedt-Sylla, E; Zrenner, E

    1998-01-01

    AIMS—To describe the topography of multifocal electroretinograms (ERGs) and to explore its diagnostic value in patients with Stargardt's macular dystrophy (SMD).
METHODS—51 patients with SMD were examined by means of the m-sequence technique to characterise the topography of electroretinographic responses in the central visual field. The results were compared with data from 30 normal volunteers.
RESULTS—In 49 of 51 patients with SMD, macular electroretinographic activity was markedly diminished or non-detectable. Towards more peripheral areas, ERG responses of the SMD patients approached those of normals. Implicit times were not markedly delayed at any eccentricity.
CONCLUSION—In contrast with Ganzfeld electroretinography, multifocal electroretinography is useful to detect foveal dysfunction in SMD. Areas of dysfunction were found to be usually larger than expected from psychophysical measurements and morphological alteration. In early stages of the disease it was possible to detect foveal dysfunction, even in patients lacking morphological fundus changes and with good visual acuity.

 Keywords: Stargardt's macular dystrophy; fundus flavimaculatus; electroretinography PMID:9602623

  14. Development of gene therapy for treatment of age-related macular degeneration.

    PubMed

    Askou, Anne Louise

    2014-07-01

    of laser-induced choroidal neovascularization (CNV), and we found that subretinal administration of self-complementary (sc)-AAV2/8 encoding anti-VEGF shRNAs can impair vessel formation. In parallel, a significant reduction of endogenous VEGF was demonstrated following injection of scAAV2/8 vectors expressing multiple anti-VEGF miRNAs into murine hind limb muscles. Furthermore, in an ongoing project we have designed versatile, multigenic LV vectors with combined expression of multiple miRNAs and proteins, including pigment epithelium-derived factor (PEDF), a multifunctional, secreted protein that has anti-angiogenic and neurotrophic functions. Co-expression of miRNAs and proteins from a single viral vector increases safety by minimizing the viral load necessary to obtain a therapeutic effect and thereby reduces the risk of insertional mutagenesis as well as the immune response against viral proteins. Our results show co-expression of functional anti-VEGF-miRNAs and PEDF in cell studies, and in vivo studies reveal an efficient retinal pigment epithelium (RPE)-specific gene expression following the incorporation of the vitelliform macular dystrophy 2 (VMD2) promoter, demonstrating the potential applicability of our multigenic LV vectors in ocular anti-VEGF gene therapy, including combination therapy for treatment of exudative AMD. In conclusion, these highly promising data clearly demonstrate that viral-encoded RNAi effector molecules can be used for the inhibition of neovascularization and will, in combination with the growing interest of applying DNA- or RNA-based technologies in the clinic, undoubtedly contribute to the development of efficacious long-term gene therapy treatment of intraocular neovascular diseases.

  15. Comparison of intravitreal bevacizumab with macular photocoagulation for treatment of diabetic macular edema: a systemic review and Meta-analysis

    PubMed Central

    Liu, Xiang-Dong; Zhou, Xiao-Dong; Wang, Zhi; Shen, Hong-Jie

    2014-01-01

    AIM To further evaluate the efficacy and safety of intravitreal bevacizumab (IVB) versus macular photocoagulation (MPC) in treatment of diabetic macular edema (DME) by Meta-analysis. METHODS Pertinent publications were identified through systemic searches of PubMed, Medline, EMBASE, and the Cochrane Controlled Trials Register up to 30 November, 2013. Changes in central macular thickness (CMT) in µm and best-corrected visual acuity (BCVA) in logMAR equivalents were extracted at 1, 3, 6, 12 and 24mo after initial treatment, and a Meta-analysis was carried out to compare results between groups receiving IVB and MPC. RESULTS Five randomized controlled trial (RCTs) and one high-quality comparative study were identified and included. Our Meta-analysis revealed that both IVB and MPC resulted in the improvements of CMT and BCVA in eyes with DME at 1mo after initial treatment, with IVB being significantly superior to MPC (P=0.01 and 0.02, respectively). The improvements of both measure outcomes at 3, 6, 12 and 24mo after treatment did not vary significantly between the IVB groups and MPC groups (CMT at 3mo, P=0.85; at 6mo, P=0.29; at 12mo, P=0.56; at 24mo, P=0.71; BCVA at 3mo, P=0.31; at 6mo, P= 0.30; at 12mo, P=0.23; at 24mo, P=0.52). However, the number of observed adverse events was low in all studies. CONCLUSION Current evidence shows IVB treatment trends to be more effective in improvements of macular edema and vision in eyes with DME at an earlier follow up (1mo) compared with MPC. At other time, both interventions have comparable efficacy without statistical significances. PMID:25540764

  16. Biallelic Mutations in the Autophagy Regulator DRAM2 Cause Retinal Dystrophy with Early Macular Involvement

    PubMed Central

    El-Asrag, Mohammed E.; Sergouniotis, Panagiotis I.; McKibbin, Martin; Plagnol, Vincent; Sheridan, Eamonn; Waseem, Naushin; Abdelhamed, Zakia; McKeefry, Declan; Van Schil, Kristof; Poulter, James A.; Black, Graeme; Hall, Georgina; Ingram, Stuart; Gillespie, Rachel; Ramsden, Simon; Manson, Forbes; Hardcastle, Alison; Michaelides, Michel; Cheetham, Michael; Arno, Gavin; Thomas, Niclas; Bhattacharya, Shomi; Moore, Tony; Nemeth, Andrea; Downes, Susan; Lise, Stefano; Lord, Emma; Johnson, Colin A.; Carr, Ian M.; Leroy, Bart P.; De Baere, Elfride; Inglehearn, Chris F.; Webster, Andrew R.; Toomes, Carmel; Ali, Manir

    2015-01-01

    Retinal dystrophies are an overlapping group of genetically heterogeneous conditions resulting from mutations in more than 250 genes. Here we describe five families affected by an adult-onset retinal dystrophy with early macular involvement and associated central visual loss in the third or fourth decade of life. Affected individuals were found to harbor disease-causing variants in DRAM2 (DNA-damage regulated autophagy modulator protein 2). Homozygosity mapping and exome sequencing in a large, consanguineous British family of Pakistani origin revealed a homozygous frameshift variant (c.140delG [p.Gly47Valfs∗3]) in nine affected family members. Sanger sequencing of DRAM2 in 322 unrelated probands with retinal dystrophy revealed one European subject with compound heterozygous DRAM2 changes (c.494G>A [p.Trp165∗] and c.131G>A [p.Ser44Asn]). Inspection of previously generated exome sequencing data in unsolved retinal dystrophy cases identified a homozygous variant in an individual of Indian origin (c.64_66del [p.Ala22del]). Independently, a gene-based case-control association study was conducted via an exome sequencing dataset of 18 phenotypically similar case subjects and 1,917 control subjects. Using a recessive model and a binomial test for rare, presumed biallelic, variants, we found DRAM2 to be the most statistically enriched gene; one subject was a homozygote (c.362A>T [p.His121Leu]) and another a compound heterozygote (c.79T>C [p.Tyr27His] and c.217_225del [p.Val73_Tyr75del]). DRAM2 encodes a transmembrane lysosomal protein thought to play a role in the initiation of autophagy. Immunohistochemical analysis showed DRAM2 localization to photoreceptor inner segments and to the apical surface of retinal pigment epithelial cells where it might be involved in the process of photoreceptor renewal and recycling to preserve visual function. PMID:25983245

  17. Stem cell based therapies for age-related macular degeneration: The promises and the challenges.

    PubMed

    Nazari, Hossein; Zhang, Li; Zhu, Danhong; Chader, Gerald J; Falabella, Paulo; Stefanini, Francisco; Rowland, Teisha; Clegg, Dennis O; Kashani, Amir H; Hinton, David R; Humayun, Mark S

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular (NV-AMD) or non-neovascular (NNV-AMD). Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD (Geographic Atrophy). In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs (e.g., anti-VEGF) are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells (hESC-RPE) and from induced pluripotent stem cells (iPSC-RPE) has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed.

  18. Prospects for clinical use of reprogrammed cells for autologous treatment of macular degeneration.

    PubMed

    Alvarez Palomo, Ana Belen; McLenachan, Samuel; Chen, Fred K; Da Cruz, Lyndon; Dilley, Rodney J; Requena, Jordi; Lucas, Michaela; Lucas, Andrew; Drukker, Micha; Edel, Michael J

    2015-01-01

    Since the discovery of induced pluripotent stem cells (iPSC) in 2006, the symptoms of many human diseases have been reversed in animal models with iPSC therapy, setting the stage for future clinical development. From the animal data it is clear that iPSC are rapidly becoming the lead cell type for cell replacement therapy and for the newly developing field of iPSC-derived body organ transplantation. The first human pathology that might be treated in the near future with iPSC is age-related macular degeneration (AMD), which has recently passed the criteria set down by regulators for phase I clinical trials with allogeneic human embryonic stem cell-derived cell transplantation in humans. Given that iPSC are currently in clinical trial in Japan (RIKEN) to treat AMD, the establishment of a set of international criteria to make clinical-grade iPSC and their differentiated progeny is the next step in order to prepare for future autologous cell therapy clinical trials. Armed with clinical-grade iPSC, we can then specifically test for their threat of cancer, for proper and efficient differentiation to the correct cell type to treat human disease and then to determine their immunogenicity. Such a rigorous approach sets a far more relevant paradigm for their intended future use than non-clinical-grade iPSC. This review focuses on the latest developments regarding the first possible use of iPSC-derived retinal pigment epithelial cells in treating human disease, covers data gathered on animal models to date and methods to make clinical-grade iPSC, suggests techniques to ensure quality control and discusses possible clinical immune responses.

  19. A local complement response by RPE causes early-stage macular degeneration

    PubMed Central

    Fernandez-Godino, Rosario; Garland, Donita L.; Pierce, Eric A.

    2015-01-01

    Inherited and age-related macular degenerations (AMDs) are important causes of vision loss. An early hallmark of these disorders is the formation of sub-retinal pigment epithelium (RPE) basal deposits. A role for the complement system in MDs was suggested by genetic association studies, but direct functional connections between alterations in the complement system and the pathogenesis of MD remain to be defined. We used primary RPE cells from a mouse model of inherited MD due to a p.R345W mutation in EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) to investigate the role of the RPE in early MD pathogenesis. Efemp1R345W RPE cells recapitulate the basal deposit formation observed in vivo by producing sub-RPE deposits in vitro. The deposits share features with basal deposits, and their formation was mediated by EFEMP1R345W or complement component 3a (C3a), but not by complement component 5a (C5a). Increased activation of complement appears to occur in response to an abnormal extracellular matrix (ECM), generated by the mutant EFEMP1R345W protein and reduced ECM turnover due to inhibition of matrix metalloproteinase 2 by EFEMP1R345W and C3a. Increased production of C3a also stimulated the release of cytokines such as interleukin (IL)-6 and IL-1B, which appear to have a role in deposit formation, albeit downstream of C3a. These studies provide the first direct indication that complement components produced locally by the RPE are involved in the formation of basal deposits. Furthermore, these results suggest that C3a generated by RPE is a potential therapeutic target for the treatment of EFEMP1-associated MD as well as AMD. PMID:26199322

  20. A local complement response by RPE causes early-stage macular degeneration.

    PubMed

    Fernandez-Godino, Rosario; Garland, Donita L; Pierce, Eric A

    2015-10-01

    Inherited and age-related macular degenerations (AMDs) are important causes of vision loss. An early hallmark of these disorders is the formation of sub-retinal pigment epithelium (RPE) basal deposits. A role for the complement system in MDs was suggested by genetic association studies, but direct functional connections between alterations in the complement system and the pathogenesis of MD remain to be defined. We used primary RPE cells from a mouse model of inherited MD due to a p.R345W mutation in EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) to investigate the role of the RPE in early MD pathogenesis. Efemp1(R345W) RPE cells recapitulate the basal deposit formation observed in vivo by producing sub-RPE deposits in vitro. The deposits share features with basal deposits, and their formation was mediated by EFEMP1(R345W) or complement component 3a (C3a), but not by complement component 5a (C5a). Increased activation of complement appears to occur in response to an abnormal extracellular matrix (ECM), generated by the mutant EFEMP1(R345W) protein and reduced ECM turnover due to inhibition of matrix metalloproteinase 2 by EFEMP1(R345W) and C3a. Increased production of C3a also stimulated the release of cytokines such as interleukin (IL)-6 and IL-1B, which appear to have a role in deposit formation, albeit downstream of C3a. These studies provide the first direct indication that complement components produced locally by the RPE are involved in the formation of basal deposits. Furthermore, these results suggest that C3a generated by RPE is a potential therapeutic target for the treatment of EFEMP1-associated MD as well as AMD.

  1. Relationship between Retinal Layer Thickness and the Visual Field in Early Age-Related Macular Degeneration

    PubMed Central

    Acton, Jennifer H.; Smith, R. Theodore; Hood, Donald C.; Greenstein, Vivienne C.

    2012-01-01

    Purpose. To quantify and compare the structural and functional changes in subjects with early age-related macular degeneration (AMD), using spectral-domain optical coherence tomography (SD-OCT) and microperimetry. Methods. Twenty-one eyes of 21 subjects with early AMD were examined. MP-1 10-2 visual fields (VFs) and SD-OCT line and detail volume scans were acquired. The thicknesses of the outer segment (OS; distance between inner segment ellipsoid band and upper retinal pigment epithelium [RPE] border) and RPE layers and elevation of the RPE from Bruch's membrane were measured using a computer-aided manual segmentation technique. Thickness values were compared with those for 15 controls, and values at locations with VF total deviation defects were compared with values at nondefect locations at equivalent eccentricities. Results. Sixteen of 21 eyes with AMD had VF defects. Compared with controls, line scans showed significant thinning of the OS layer (P = 0.006) and thickening and elevation of the RPE (P = 0.037, P = 0.002). The OS layer was significantly thinner in locations with VF defects compared with locations without defects (P = 0.003). There was a negligible difference between the retinal layer thickness values of the 5 eyes without VF defects and the values of normal controls. Conclusions. In early AMD, when VF defects were present, there was significant thinning of the OS layer and thickening and elevation of the RPE. OS layer thinning was significantly associated with decreased visual sensitivity, consistent with known photoreceptor loss in early AMD. For AMD subjects without VF defects, thickness values were normal. The results highlight the clinical utility of both SD-OCT retinal layer quantification and VF testing in early AMD. PMID:23074210

  2. Insights into the mechanisms of macular degeneration associated with the R172W mutation in RDS

    PubMed Central

    Conley, Shannon M.; Stuck, Michael W.; Burnett, Justin L.; Chakraborty, Dibyendu; Azadi, Seifollah; Fliesler, Steven J.; Naash, Muna I.

    2014-01-01

    Mutations in the photoreceptor tetraspanin gene peripherin-2/retinal degeneration slow (PRPH2/RDS) cause both rod- and cone-dominant diseases. While rod-dominant diseases, such as autosomal dominant retinitis pigmentosa, are thought to arise due to haploinsufficiency caused by loss-of-function mutations, the mechanisms underlying PRPH2-associated cone-dominant diseases are unclear. Here we took advantage of a transgenic mouse line expressing an RDS mutant (R172W) known to cause macular degeneration (MD) in humans. To facilitate the study of cones in the heavily rod-dominant mouse retina, R172W mice were bred onto an Nrl−/− background (in which developing rods adopt a cone-like fate). In this model the R172W protein and the key RDS-binding partner, rod outer segment (OS) membrane protein 1 (ROM-1), were properly expressed and trafficked to cone OSs. However, the expression of R172W led to dominant defects in cone structure and function with equal effects on S- and M-cones. Furthermore, the expression of R172W in cones induced subtle alterations in RDS/ROM-1 complex assembly, specifically resulting in the formation of abnormal, large molecular weight ROM-1 complexes. Fundus imaging demonstrated that R172W mice developed severe clinical signs of disease nearly identical to those seen in human MD patients, including retinal degeneration, retinal pigment epithlium (RPE) defects and loss of the choriocapillaris. Collectively, these data identify a primary disease-causing molecular defect in cone cells and suggest that RDS-associated disease in patients may be a result of this defect coupled with secondary sequellae involving RPE and choriocapillaris cell loss. PMID:24463884

  3. Current and emerging therapies for the treatment of age-related macular degeneration.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2008-06-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV) due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF) therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA) to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary neurotrophic factor is currently being studied for the inhibition of progression of geographic atrophy. Combination therapy has been

  4. Non-photosynthetic pigments as potential biosignatures

    NASA Astrophysics Data System (ADS)

    Schwieterman, E. W.; Cockell, C. S.; Meadows, V. S.

    2014-03-01

    Photosynthetic organisms on Earth produce potentially detectable surface reflectance biosignatures due in part to the spectral location and strength of pigment absorption. However, life on Earth uses pigments for a multitude of purposes other than photosynthesis, including coping with extreme environments. Macroscopic environments exist on Earth where the surface reflectance is significantly altered by a nonphotosynthetic pigment, such as the case of hypersaline lakes and ponds (Oren et al. 1992). Here we explore the nature and potential detectability of non-photosynthetic pigments in disk-averaged planetary observations using a combination of laboratory measurements and archival reflectance spectra, along with simulated broadband photometry and spectra. The in vivo visible reflectance spectra of a cross section of pigmented microorganisms are presented to illustrate the spectral diversity of biologically produced pigments. Synthetic broadband colors are generated to show a significant spread in color space. A 1D radiative transfer model (Meadows & Crisp 1996; Crisp 1997) is used to approximate the spectra of scenarios where pigmented organisms are widespread on planets with Earth-like atmospheres. Broadband colors are revisited to show that colors due to surface reflectivity are not robust to the addition of scattering and absorption effects from the atmosphere. We consider a èbest case' plausible scenario for the detection of nonphotosynthetic pigments by using the Virtual Planetary Laboratory's 3D spectral Earth model (Robinson et al. 2011) to explore the detectability of the surface biosignature produced by pigmented halophiles that are widespread on an Earth-analog planet.

  5. Melanin pigmented solar absorbing surfaces

    SciTech Connect

    Gallas, J.M.; Eisner, M.

    1980-01-01

    Selectivity enhancement is shown to result for melanin, a black biopolymer pigment, for sufficiently low sample density. The effect is proposed to follow from a consideration of the evanescent waves associated with the total internal reflection phenomenon. A relationship is discussed among powder density, pH and the paramagnetic properties of melanin; this relationship is shown to be consistent with, and offer support to an amino-acid side group proposed earlier as part of the melanin structure. A brief discussion is also presented on the optical properties of melanin and the relative importance of quinhydrone, a change transfer complex believed to exist in the polymeric structure of melanin.

  6. Pigmented Lesion of Buccal Mucosa

    PubMed Central

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  7. Iris pigmentation and behavioral inhibition.

    PubMed

    Rosenberg, A; Kagan, J

    1987-07-01

    Two independent investigations of the association between the temperamental dimensions of inhibition and lack of inhibition to the unfamiliar, on the one hand, and the degree of pigmentation of the iris, on the other, revealed a statistically significant relation in Caucasian children between behavioral inhibition to the unfamiliar and blue irises and uninhibited behavior and brown irises. Several biochemical interpretations of this association were discussed and it was suggested that these behavioral styles might be influenced by biological factors that are partially marked by eye color in Caucasian populations.

  8. Macular pattern dystrophy and homonymous hemianopia in MELAS syndrome.

    PubMed

    Kamal-Salah, Radua; Baquero-Aranda, Isabel; Grana-Pérez, María Del Mar; García-Campos, Jose Manuel

    2015-03-12

    We report an unusual association of a pattern dystrophy of the retinal pigment epithelium and homonymous hemianopia in a woman diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome.

  9. Macular pattern dystrophy and homonymous hemianopia in MELAS syndrome.

    PubMed

    Kamal-Salah, Radua; Baquero-Aranda, Isabel; Grana-Pérez, María Del Mar; García-Campos, Jose Manuel

    2015-01-01

    We report an unusual association of a pattern dystrophy of the retinal pigment epithelium and homonymous hemianopia in a woman diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome. PMID:25766436

  10. 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

  11. Detecting abnormalities in choroidal vasculature in a mouse model of age-related macular degeneration by time-course indocyanine green angiography.

    PubMed

    Kumar, Sandeep; Berriochoa, Zachary; Jones, Alex D; Fu, Yingbin

    2014-02-19

    Indocyanine Green Angiography (or ICGA) is a technique performed by ophthalmologists to diagnose abnormalities of the choroidal and retinal vasculature of various eye diseases such as age-related macular degeneration (AMD). ICGA is especially useful to image the posterior choroidal vasculature of the eye due to its capability of penetrating through the pigmented layer with its infrared spectrum. ICGA time course can be divided into early, middle, and late phases. The three phases provide valuable information on the pathology of eye problems. Although time-course ICGA by intravenous (IV) injection is widely used in the clinic for the diagnosis and management of choroid problems, ICGA by intraperitoneal injection (IP) is commonly used in animal research. Here we demonstrated the technique to obtain high-resolution ICGA time-course images in mice by tail-vein injection and confocal scanning laser ophthalmoscopy. We used this technique to image the choroidal lesions in a mouse model of age-related macular degeneration. Although it is much easier to introduce ICG to the mouse vasculature by IP, our data indicate that it is difficult to obtain reproducible ICGA time course images by IP-ICGA. In contrast, ICGA via tail vein injection provides high quality ICGA time-course images comparable to human studies. In addition, we showed that ICGA performed on albino mice gives clearer pictures of choroidal vessels than that performed on pigmented mice. We suggest that time-course IV-ICGA should become a standard practice in AMD research based on animal models.

  12. One-year outcome of intravitreal aflibercept injection for age-related macular degeneration resistant to ranibizumab: rapid morphologic recovery and subsequent visual improvement

    PubMed Central

    Hirakata, Toshiaki; Fujinami, Kaoru; Watanabe, Ken; Sasaki, Mariko; Noda, Toru; Akiyama, Kunihiko

    2016-01-01

    Objective To describe the 1-year efficacy of aflibercept in Japanese patients with age-related macular degeneration (AMD) who were resistant to ranibizumab treatment. Design Retrospective case series. Participants Fourteen consecutive eyes of 14 patients with AMD were enrolled who had no substantial response or developed resistance to intravitreal ranibizumab injections. Methods All patients were subcategorized into one of two subtypes of AMD: seven patients with occult choroidal neovascularization (CNV) and seven with polypoidal choroidal vasculopathy (PCV). Serial intravitreal aflibercept (IVA) injections were administered. Comprehensive ophthalmic examinations, including optical coherence tomography, were conducted at baseline and at follow-up examinations at 1, 3, 6, and 12 months after the initial IVA injection. The best-corrected visual acuity converted to logarithm of the minimum angle of resolution (logMAR) and central macular thickness (CMT) at each follow-up visit were compared with the baseline values. The anatomic response was also assessed with absorption or reduction of fluid in the subretina or subretinal pigment epithelial space. Results The logMAR best-corrected visual acuity improved significantly at 3, 6, and 12 months in the total cohort: at 3 and 6 months in patients with occult CNV and at 3 and 12 months in patients with PCV. The CMT decreased significantly at all follow-up visits in the total cohort as well as in both subtypes, except for the CMT at 6 months in PCV patients. The anatomic improvement was also demonstrated in all cases, and pigment epithelial detachments tended to be resolved more rapidly in patients with PCV than in patients with occult CNV. Conclusion Conversion to IVA was effective in patients with AMD resistant to ranibizumab, showing rapid morphologic improvement. The logMAR visual acuity was raised significantly within 12 months, and the clinical course of visual acuity improvement may differ according to the AMD subtypes

  13. Variability of surface pigment concentrations in the South Atlantic Bight

    NASA Technical Reports Server (NTRS)

    Mcclain, Charles R.; Yoder, James A.; Blanton, J. O.; Atkinson, L. P.; Lee, T. N.

    1988-01-01

    A time sequence of surface pigment images of the South Atlantic Bight (SAB), derived from the Nimbus 7 CZCS for the period between November 1978 and October 1979, was correlated with in situ observations of hydrographic parameters, fresh-water discharge, sea level, coastal winds, and currents in order to couple physical processes and the spatial and temporal variability of the surface pigment fields. A definite seasonal modulation of the surface pigment fields was found, with the concentrations in the Georgia Bight being highest in summer, and those north of Cape Romain highest in winter. This phase difference was found to be the result of variations in wind fields, Gulf Stream-shelf interactions, and fresh-water discharge patterns. At some locations (e.g., near Charleston) the alongshore band of high pigment concentrations increased in width throughout the year; at other locations (near Jacksonville), the alongsore band exhibited a minimum width in the summer and a maximum width in the fall of 1979.

  14. Social stress effects on pigmentation and monoamines in Arctic charr.

    PubMed

    Backström, Tobias; Heynen, Martina; Brännäs, Eva; Nilsson, Jan; Winberg, Svante; Magnhagen, Carin

    2015-09-15

    Pigmentation often signals status and in general melanin-based pigmentation is indicative of aggression and stress resilience in vertebrates. This is evident in the salmonids Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) where more melanin spotted individuals are more stress resilient. However, in the salmonid Arctic charr (Salvelinus alpinus) it seems as if it is carotenoid-based pigmentation that signals aggression and stress resilience. In our study, social stress effects on carotenoid-based spots, and behavioural and physiological stress responses were investigated. Socially stressed individuals have more spots, and behavioural stress responses were associated with spots. Some of the results concerning physiological stress responses, such as plasma cortisol levels and monoaminergic activity, are associated with spottiness. Further, the earlier proposed lateralization of spots, with left side connected to stress responsiveness and right side to aggression, is to some extent validated although not conclusively. In conclusion, this study provides further evidence that more stressed charr have more carotenoid spots, and for the first time monoaminergic activity is shown to be connected with carotenoid pigmentation.

  15. Continental variation in wing pigmentation in Calopteryx damselflies is related to the presence of heterospecifics.

    PubMed

    Hassall, Christopher

    2014-01-01

    Wing pigmentation in Calopteryx damselflies, caused by the deposition of melanin, is energetically expensive to produce and enhances predation risk. However, patterns of melanisation are used in species identification, greater pigmentation is an accurate signal of male immune function in at least some species, and there may be a role for pigment in thermoregulation. This study tested two potential hypotheses to explain the presence of, and variation in, this pigmentation based on these three potential benefits using 907 male specimens of Calopteryx maculata collected from 49 sites (34 discrete populations) across the geographical range of the species in North America: (i) pigmentation varies with the presence of the closely related species, Calopteryx aequabilis, and (ii) pigment increases at higher latitudes as would be expected if it enhances thermoregulatory capacity. No gradual latitudinal pattern was observed, as might be expected if pigmentation was involved in thermoregulation. However, strong variation was observed between populations that were sympatric or allopatric with C. aequabilis. This variation was characterised by dark wings through allopatry in the south of the range and then a step change to much lighter wings at the southern border of sympatry. Pigmentation then increased further north into the sympatric zone, finally returning to allopatry levels at the northern range margin. These patterns are qualitatively similar to variation in pigmentation in C. aequabilis, meaning that the data are consistent with what would be expected from convergent character displacement. Overall, the results corroborate recent research that has suggested sexual selection as a primary driver behind the evolution of wing pigmentation in this group.

  16. Continental variation in wing pigmentation in Calopteryx damselflies is related to the presence of heterospecifics

    PubMed Central

    2014-01-01

    Wing pigmentation in Calopteryx damselflies, caused by the deposition of melanin, is energetically expensive to produce and enhances predation risk. However, patterns of melanisation are used in species identification, greater pigmentation is an accurate signal of male immune function in at least some species, and there may be a role for pigment in thermoregulation. This study tested two potential hypotheses to explain the presence of, and variation in, this pigmentation based on these three potential benefits using 907 male specimens of Calopteryx maculata collected from 49 sites (34 discrete populations) across the geographical range of the species in North America: (i) pigmentation varies with the presence of the closely related species, Calopteryx aequabilis, and (ii) pigment increases at higher latitudes as would be expected if it enhances thermoregulatory capacity. No gradual latitudinal pattern was observed, as might be expected if pigmentation was involved in thermoregulation. However, strong variation was observed between populations that were sympatric or allopatric with C. aequabilis. This variation was characterised by dark wings through allopatry in the south of the range and then a step change to much lighter wings at the southern border of sympatry. Pigmentation then increased further north into the sympatric zone, finally returning to allopatry levels at the northern range margin. These patterns are qualitatively similar to variation in pigmentation in C. aequabilis, meaning that the data are consistent with what would be expected from convergent character displacement. Overall, the results corroborate recent research that has suggested sexual selection as a primary driver behind the evolution of wing pigmentation in this group. PMID:24949250

  17. 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

  18. Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment Epithelium Cells.

    PubMed

    Merl-Pham, Juliane; Gruhn, Fabian; Hauck, Stefanie M

    2016-01-01

    Age-related macular degeneration (AMD) is a medical condition usually affecting older adults and resulting in a loss of vision in the macula, the center of the visual field. The dry form of this disease presents with atrophy of the retinal pigment epithelium, resulting in the detachment of the retina and loss of photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases the risk of developing the disease by three times. In order to understand the influence of cigarette smoke on retinal pigment epithelial cells, cultured human ARPE-19 cells were treated with cigarette smoke extract for 24 h. Using quantitative mass spectrometry more than 3000 proteins were identified and their respective abundances were compared between cigarette smoke-treated and untreated cells. Altogether 1932 proteins were quantified with at least two unique peptides, with 686 proteins found to be significantly differentially abundant with p > 0.05. Of these proteins the abundance of 64 proteins was at least 2-fold down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up-regulated. The analysis of associated biological processes revealed an alteration of proteins involved in RNA processing and transport as well as extracellular matrix remodelling in response to cigarette smoke treatment.

  19. Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment Epithelium Cells.

    PubMed

    Merl-Pham, Juliane; Gruhn, Fabian; Hauck, Stefanie M

    2016-01-01

    Age-related macular degeneration (AMD) is a medical condition usually affecting older adults and resulting in a loss of vision in the macula, the center of the visual field. The dry form of this disease presents with atrophy of the retinal pigment epithelium, resulting in the detachment of the retina and loss of photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases the risk of developing the disease by three times. In order to understand the influence of cigarette smoke on retinal pigment epithelial cells, cultured human ARPE-19 cells were treated with cigarette smoke extract for 24 h. Using quantitative mass spectrometry more than 3000 proteins were identified and their respective abundances were compared between cigarette smoke-treated and untreated cells. Altogether 1932 proteins were quantified with at least two unique peptides, with 686 proteins found to be significantly differentially abundant with p > 0.05. Of these proteins the abundance of 64 proteins was at least 2-fold down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up-regulated. The analysis of associated biological processes revealed an alteration of proteins involved in RNA processing and transport as well as extracellular matrix remodelling in response to cigarette smoke treatment. PMID:26427490

  20. Late Closure of a Stage III Idiopathic Macular Hole after Pars Plana Vitrectomy

    PubMed Central

    Afrashi, Filiz; Öztaş, Zafer; Nalçacı, Serhad

    2015-01-01

    A 57-year-old female presented to our hospital with decreased vision in her right eye. Detailed ocular examination was performed, and a macular hole was detected in the right eye. The presence of a full-thickness stage III macular hole was confirmed with optical coherence tomography (OCT) imaging. Pars plana vitrectomy followed by long-acting gas tamponade (C3F8) was performed as treatment. One month after surgery, clinical examination revealed a persistent macular hole, confirmed by an OCT scan. Although the patient was scheduled for reoperation, the surgery was postponed due to personal reasons of the patient. Surprisingly, after five months, a closure pattern with accompanying epiretinal membrane was observed in the macular hole area. The closure of the macular hole was completed without any further intervention 8 months post-surgery. In cases of unclosed macular hole after the first surgery, if a second surgery cannot be performed, follow-up with OCT recommended due to the possibility of spontaneous closure. However, spontaneous closure of a persistent macular hole following PPV is rare, so early diagnosis and surgical repair of unclosed macular holes must remain the primary goal. PMID:27800248

  1. Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism.

    PubMed

    Onojafe, Ighovie F; Adams, David R; Simeonov, Dimitre R; Zhang, Jun; Chan, Chi-Chao; Bernardini, Isa M; Sergeev, Yuri V; Dolinska, Monika B; Alur, Ramakrishna P; Brilliant, Murray H; Gahl, William A; Brooks, Brian P

    2011-10-01

    Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with the latter produce some melanin. We hypothesized that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved inhibitor of tyrosine degradation, could stabilize tyrosinase and improve pigmentation in individuals with OCA1. Here, we tested this hypothesis in mice homozygous for either the Tyrc-2J null allele or the Tyrc-h allele, which model OCA-1A and OCA-1B, respectively. Only nitisinone-treated Tyrc-h/c-h mice manifested increased pigmentation in their fur and irides and had more pigmented melanosomes. High levels of tyrosine improved the stability and enzymatic function of the Tyrc-h protein and also increased overall melanin levels in melanocytes from a human with OCA-1B. These results suggest that the use of nitisinone in OCA-1B patients could improve their pigmentation and potentially ameliorate vision loss. PMID:21968110

  2. IV. HEMOGLOBIN INJECTIONS AND CONSERVATION OF PIGMENT BY KIDNEY, LIVER AND SPLEEN : THE INFLUENCE OF DIET AND BLEEDING.

    PubMed

    Newman, W V; Whipple, G H

    1932-03-31

    When the minimal renal threshold for blood hemoglobin is exceeded there is observed a deposit of iron staining pigment in the epithelium of the renal convoluted tubules. At a certain point this epithelium cannot take up more hemoglobin and this coincides with the minimal renal threshold level. When the injections of blood hemoglobin are kept below the minimal renal threshold level we note a complete absence of iron staining pigment in the renal tubular epithelium. Given a deposit of iron staining pigment in the tubular epithelium, it will slowly disappear during rest periods with no hemoglobin injections. Anemia due to bleeding will accelerate this removal of pigment from the renal epithelium and this indicates a conservation of material by the kidney for use in construction of new hemoglobin. Pigment giving a positive stain for iron will be found in the liver and spleen when hemoglobin injections are given, regardless of the renal threshold. Removal of this pigment is accelerated by anemia due to bleeding and as a rule an anemia period of 2 months at a level of 1/3 normal (40 to 50 per cent hemoglobin) will render the spleen, liver and kidney free from iron staining pigment. Pigment giving a positive iron stain is frequently observed in the mesenteric and lower retroperitoneal lymph glands. This is merely a drainage of pigment and phagocytes including pigment from some organ in which the pigment deposit was primary. In stock dogs in this laboratory the hemoglobin level is quite high when the animals are in a perfectly normal state. The blood hemoglobin averages 120 to 150 per cent hemoglobin. In such dogs iron staining pigment in the spleen is a common finding and on occasion is observed in the liver. To establish an accurate base line for the study of iron and iron staining pigment storage due to diet intake one must submit these dogs to a preliminary anemia period of at least 2 months. Muscle hemoglobin has a very low renal threshold and escapes freely into the

  3. The bioefficacy of microemulsified natural pigments in egg yolk pigmentation.

    PubMed

    Chow, P Y; Gue, S Z; Leow, S K; Goh, L B

    2014-01-01

    1. This study was designed to test the hypothesis that microemulsified carotenoid products show improved bioavailability over corresponding regular preparations, leading to greater yolk pigmentation at lower dosages. 2. The first trial was conducted using a maize-soya bean basal diet supplemented with either 0.25, 0.5, 0.75, 1.0 and 1.25 g/kg of microemulsified Red or non-microemulsified Red. The second trial involved feeding microemulsified Yellow or non-microemulsified Yellow using a similar dosage range. The layers were divided into 4 replicates of 8 layers each (32 layers per treatment). The 8 cages of layers were fed from a single feed trough. Feed and water were provided ad libitum throughout the trial. Each week, the eggs were collected. The whole liquid egg colour was determined by means of a commercially available yolk colour fan. Where required, HPLC-(high-performance liquid chromatography) based analysis of trans-capsanthin or trans-lutein equivalents using the Association of Analytical Communities method was carried out. Data were statistically analysed by one-way ANOVA method using Statgraphics. 3. Results showed that the colour and carotenoid content of the egg yolk increased with increasing amount of carotenoids in the diet. The colour of egg yolks from layers fed similar concentrations of microemulsified versus the regular preparation was significantly different. At the commercial recommended dose of one g/kg regular Yellow or Red product, the microemulsified pigmenter is able to provide the equivalent yolk colour at a 20-30% lower dose. 4. In conclusion, the trial results supported the hypothesis that a desired yolk colour score is achievable at a significantly lower inclusion rate when carotenoid molecules are emulsified using the microemulsion nanotechnology.

  4. The spleen pigment cells in some amphibia.

    PubMed

    Scalia, Marina; Di Pietro, Cinzia; Poma, Mariangela; Ragusa, Marco; Sichel, Giovanni; Corsaro, Concetta

    2004-04-01

    It was demonstrated that the spleen pigment cells of Amphibia are macrophages: they show an ultrastructurally distinctive morphology, are able to phagocytose and react positively for non-specific esterases. These pigmented macrophages express mRNA for tyrosinase and also they show dopa oxidase activity; therefore they are able to synthesize melanins, as Kupffer cells do.

  5. Thin Layer Chromatography (TLC) of Chlorophyll Pigments.

    ERIC Educational Resources Information Center

    Foote, Jerry

    1984-01-01

    Background information, list of materials needed, procedures used, and discussion of typical results are provided for an experiment on the thin layer chromatography of chlorophyll pigments. The experiment works well in high school, since the chemicals used are the same as those used in paper chromatography of plant pigments. (JN)

  6. Dermatoscopic findings of pigmented purpuric dermatosis*

    PubMed Central

    Ozkaya, Dilek Biyik; Emiroglu, Nazan; Su, Ozlem; Cengiz, Fatma Pelin; Bahali, Anil Gulsel; Yildiz, Pelin; Demirkesen, Cuyan; Onsun, Nahide

    2016-01-01

    Background Pigmented purpuric dermatosis is a chronic skin disorder of unknown aetiology characterised by symmetrical petechial and pigmented macules, often confined to the lower limbs. The aetiology of pigmented purpuric dermatosis is unknown. Dermatoscopy is a non-invasive diagnostic technique that allows the visualisation of morphological features invisible to the naked eye; it combines a method that renders the corneal layer of the skin translucent with an optical system that magnifies the image projected onto the retina. Objectives The aim of this study is to investigate the dermatoscopic findings of pigmented purpuric dermatosis. Methods This study enrolled patients diagnosed histopathologically with pigmented purpuric dermatosis who had dermatoscopic records. We reviewed the dermatoscopic images of PPD patients who attended the outpatient clinic in the Istanbul Dermatovenereology Department at the Bezmialem Vakıf University Medical Faculty. Results Dermatoscopy showed: coppery-red pigmentation (97%, n = 31) in the background, a brown network (34%, n = 11), linear vessels (22%, n = 7), round to oval red dots, globules, and patches (69%, n = 22; 75%, n = 24; 34%, n = 11; respectively), brown globules (26%, n = 8) and dots (53%, n = 17), linear brown lines (22%, n = 7), and follicular openings (13%, n = 4). Conclusion To our knowledge, this is the first study to report the dermatoscopy of pigmented purpuric dermatosis. In our opinion, dermatoscopy can be useful in the diagnosis of pigmented purpuric dermatosis.

  7. Developing fungal pigments for "painting" vascular plants.

    PubMed

    Robinson, Sara C

    2012-02-01

    The use of fungal pigments as color additives to wood as a method to increase forest revenue is a relatively new, but quickly developing field. Sugar maple (Acer saccharum) is currently the primary utilized hardwood for spalting and appears to be the best suited North American hardwood for such purposes. The combination of Trametes versicolor and Bjerkandera adusta has been identified in several instances as a strong fungal pairing for zone line production; however, Xylaria polymorpha is capable of creating zone lines without the antagonism of a secondary fungus. Few fungal pigments have been developed for reliable use; Scytalidium cuboideum is capable of producing a penetrating pink/red stain, as well as a blue pigment after extended incubation, and Chlorociboria sp. produces a blue/green pigment if grown on aspen (Populus tremuloides). Several opportunities exist for stimulation of fungal pigments including the use of copper sulfate and changes in wood pH. PMID:22237673

  8. Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines expression and activates relevant signal pathways in primary human retinal pigment epithelial cells.

    PubMed

    Shen, Ye; Xie, Chen; Gu, Yangshun; Li, Xiuyi; Tong, Jianping

    2016-04-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the aged people. The latest systemic review of epidemiological investigations revealed that excessive light exposure increases the risk of AMD. With the drastically increasing use of high-energy light-emitting diodes (LEDs) light in our domestic environment nowadays, it is supposed to pose a potential oxidative threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular source of pathological cytokines, which regulate local inflammation and angiogenesis. We hypothesized that high-energy LED light might disrupt the pathological cytokine expression of retinal pigment epithelium (RPE), contributing to the pathogenesis of AMD. Primary human RPE cells were isolated from eyecups of normal eye donors and seeded into plate wells for growing to confluence. Two widely used multichromatic white light-emitting diodes (LEDs) with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this experiment. The confluent primary RPE cells were under white LEDs light exposure until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-κB signal pathways after LEDs illumination were evaluated by western blotting analysis. The level of reactive oxygen species (ROS) using chloromethyl- 2',7'-dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and anti-oxidants were added to the primary RPE cells before LEDs illumination to evaluate their biological functions. We found that 7378 K light, but not 2954 K upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs levels in a time-dependent manner. In parallel, initial activation of MAPKs and NF-κB signal pathways were also observed after 7378 K light exposure. Mechanistically, antioxidants for eliminating reactive oxygen

  9. Honeycomb porous films as permeable scaffold materials for human embryonic stem cell-derived retinal pigment epithelium.

    PubMed

    Calejo, Maria Teresa; Ilmarinen, Tanja; Jongprasitkul, Hatai; Skottman, Heli; Kellomäki, Minna

    2016-07-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries, characterised by the degeneration of the retinal pigment epithelium (RPE), a pigmented cell monolayer that closely interacts with the photoreceptors. RPE transplantation is thus considered a very promising therapeutic option to treat this disease. In this work, porous honeycomb-like films are for the first time investigated as scaffold materials for human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). By changing the conditions during film preparation, it was possible to produce films with homogeneous pore distribution and adequate pore size (∼3-5 µm), that is large enough to ensure high permeability but small enough to enable cell adherence and spreading. A brief dip-coating procedure with collagen type IV enabled the homogeneous adsorption of the protein to the walls and bottom of pores, increasing the hydrophilicity of the surface. hESC-RPE adhered and proliferated on all the collagen-coated materials, regardless of small differences in pore size. The differentiation of hESC-RPE was confirmed by the detection of specific RPE protein markers. These results suggest that the porous honeycomb films can be promising candidates for hESC-RPE tissue engineering, importantly enabling the free flow of ions and molecules across the material. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1646-1656, 2016.

  10. Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration

    PubMed Central

    Keles, Sadullah; Ates, Orhan; Kartal, Baki; Alp, Hamit Hakan; Ekinci, Metin; Ceylan, Erdinc; Ondas, Osman; Arpali, Eren; Dogan, Semih; Yildirim, Kenan; Keles, Mevlut Sait

    2014-01-01

    Aim To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA), and nitric oxide (NO), as well as activity of endothelial NO synthase (eNOS), in patients with age-related macular degeneration (AMD). Methods The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30) were compared to a control group with no retinal pathology (n=30). Results Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.001), whereas NO levels and eNOS activity were higher in the control group (P<0.001). In the wet AMD group, we detected a 2.64- and 0.33-fold increase in the levels of ADMA and homocysteine, respectively, and a 0.49- and 2.41-fold decrease in the eNOS activity and NO level, respectively. Conclusion Elevated levels of homocysteine and ADMA were observed in patients with wet AMD. Increased ADMA may be responsible for the diminished eNOS activity found in these patients, which in turn contributes to the decrease in NO levels, which likely plays a role in the pathogenesis of AMD. PMID:25210424

  11. Inflammation and Macular Oedema after Pars Plana Vitrectomy

    PubMed Central

    Romano, Vito; Angi, Martina; del Grosso, Renata; Romano, Davide; Vinciguerra, Paolo; Romano, Mario R.

    2013-01-01

    Cystoid macular oedema (CMO) is a major cause of reduced vision following intraocular surgery. Although the aetiology of CMO is not completely clarified, intraocular inflammation is known to play a major role in its development. The macula may develop cytotoxic oedema when the primary lesion and fluid accumulation occur in the parenchymatous cells (intracellular oedema) or vasogenic oedema when the primary defect occurs in the blood-retinal barrier and leads to extracellular fluid accumulation (extracellular oedema). We report on the mechanisms of CMO formation after pars plana vitrectomy and associated surgical procedures and discuss possible therapeutic approaches. PMID:24288446

  12. Dexamethasone intravitreal implant in the treatment of diabetic macular edema.

    PubMed

    Dugel, Pravin U; Bandello, Francesco; Loewenstein, Anat

    2015-01-01

    Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood-retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ≥25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (<2

  13. [Glaucoma and age-related macular degeneration intricacy].

    PubMed

    Valtot, F

    2008-07-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness among the elderly in Western nations. Age is also a well-known and well-evidenced risk factor for glaucoma. With increasing longevity and the rising prevalence of older people around the world, more and more patients will have glaucoma and AMD. Clinical evaluation of these patients still poses problems for clinicians. It is very important to order the right tests at the right time to distinguish glaucomatous defects from those caused by retinal lesions, because appropriate therapy has a beneficial effect on slowing or halting damage. PMID:18957915

  14. Multifocal fibrosclerosis associated with suprasellar and macular lesions.

    PubMed Central

    Brazier, D J; Sanders, M D

    1983-01-01

    Multifocal fibrosclerosis is a term used to denote a combination of similar fibrous disorders occurring at different anatomical sites and including idiopathic mediastinal and retroperitoneal fibrosis, sclerosing cholangitis, Riedel's thyroiditis, and orbital pseudotumour. This paper reports a patient, known to have retroperitoneal and testicular fibrosis, who suffered visual loss resulting from marked changes in the macular region of one eye and suprasellar extension of a mass in the pituitary fossa. These lesions appear to represent very uncommon manifestations of multifocal fibrosclerosis. Images PMID:6838800

  15. The yellow mutation in the frog Rana rugosa: pigment organelle deformities in the three types of chromatophore.

    PubMed

    Ichikawa, Y; Ohtani, H; Miura, I

    2001-08-01

    Crossing experiments revealed that a single recessive gene mutation (yellow) gives rise to the yellow phenotype of Rana rugosa in Japan. Ultrastructural observation of dermal chromatophores showed that the pigment organelles; melanosomes, pterinosomes, and reflecting platelets, all had structural deformities. This suggests that the yellow gene acts at the level of a primordial pigment organelle common to the three types of chromatophore.

  16. Structure of plant bile pigments

    SciTech Connect

    Schoenleber, R.W.

    1983-12-01

    Selective peptide cleavage has provided a general procedure for the study of the structure, including stereochemistry, of plant bile pigments. The information derived from the synthesis and spectral analysis of a series of 2,3-dihydrodioxobilins allows the determination of the trans relative stereochemistry for ring A of the ..beta../sub 1/-phycocyanobilin from C-phycocyanin as well as for ring A of phytochrome. A complete structure proof of the five phycoerythrobilins attached to the ..cap alpha.. and ..beta.. subunits of B-phycoerythrin is described. One of these tetrapyrroles is doubly-peptide linked to a single peptide chain through two thioethers at the C-3' and C-18' positions. The four remaining phycoerythrobilins are singly-linked to the protein through thioethers at the C-3' position and all possess the probable stereochemistry C-2(R), C-3(R), C-3'(R), and C-16(R).

  17. A non-linear irreversible thermodynamic perspective on organic pigment proliferation and biological evolution

    NASA Astrophysics Data System (ADS)

    Michaelian, K.

    2013-12-01

    The most important thermodynamic work performed by life today is the dissipation of the solar photon flux into heat through organic pigments in water. From this thermodynamic perspective, biological evolution is thus just the dispersal of organic pigments and water throughout Earth's surface, while adjusting the gases of Earth's atmosphere to allow the most intense part of the solar spectrum to penetrate the atmosphere and reach the surface to be intercepted by these pigments. The covalent bonding of atoms in organic pigments provides excited levels compatible with the energies of these photons. Internal conversion through vibrational relaxation to the ground state of these excited molecules when in water leads to rapid dissipation of the solar photons into heat, and this is the major source of entropy production on Earth. A non-linear irreversible thermodynamic analysis shows that the proliferation of organic pigments on Earth is a direct consequence of the pigments catalytic properties in dissipating the solar photon flux. A small part of the energy of the photon goes into the production of more organic pigments and supporting biomass, while most of the energy is dissipated and channeled into the hydrological cycle through the latent heat of vaporization of surface water. By dissipating the surface to atmosphere temperature gradient, the hydrological cycle further increases the entropy production of Earth. This thermodynamic perspective of solar photon dissipation by life has implications to the possibility of finding extra-terrestrial life in our solar system and the Universe.

  18. Pigments, Parasites and Personalitiy: Towards a Unifying Role for Steroid Hormones?

    PubMed Central

    Kittilsen, Silje; Johansen, Ida Beitnes; Braastad, Bjarne Olai; Øverli, Øyvind

    2012-01-01

    A surging interest in the evolution of consistent trait correlations has inspired research on pigment patterns as a correlate of behavioural syndromes, or “animal personalities”. Associations between pigmentation, physiology and health status are less investigated as potentially conserved trait clusters. In the current study, lice counts performed on farmed Atlantic salmon Salmo salar naturally infected with ectoparasitic sea lice Lepeophtheirus salmonis showed that individual fish with high incidence of black melanin-based skin spots harboured fewer female sea lice carrying egg sacs, compared to less pigmented fish. There was no significant association between pigmentation and lice at other developmental stages, suggesting that host factors associated with melanin-based pigmentation may modify ectoparasite development to a larger degree than settlement. In a subsequent laboratory experiment a strong negative correlation between skin spots and post-stress cortisol levels was revealed, with less pigmented individuals showing a more pronounced cortisol response to acute stress. The observation that lice prevalence was strongly increased on a fraction of sexually mature male salmon which occurred among the farmed fish further supports a role for steroid hormones as mediators of reduced parasite resistance. The data presented here propose steroid hormones as a proximate cause for the association between melanin-based pigmentation and parasites. Possible fundamental and applied implications are discussed. PMID:22493685

  19. [The genetic variability of complement system in pathogenesis of age-related macular degeneration].

    PubMed

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Dziedzina, Sylwia; Sanak, Marek

    2015-01-01

    Age-related macular degeneration is the leading cause of irreversible central vision impairment in people aged over 50 in developed countries. Age-related macular degeneration is a complex disease derived from environmental, immune and genetic factors. The complement pathway has been implicated in the pathogenesis of many diseases. Recently, variants in several genes, such as complement H (CFH), complement factor B (CFB), complement 2 (C2), and complement 3 (C3), encoding complement pathway proteins, have been identified as associated with age-related macular degeneration. However, the associations between these genes and age-related macular degeneration varied due to genetic variation within populations and various ethnics groups. The strongest association was found between the age-related macular degeneration and SNP Y402H rs 1061170 variant of CFH gene, which is present in 30% to 50% of age-related macular degeneration patients in Caucasian population and which is a risk factor for the development of age-related macular degeneration. Cohort studies showed that polymorphism Arg102Gly (SNP rs 2230199) of C3 protein could serve as a high-risk genetic marker for the development of age-related macular degeneration. Other rare variants of C3 (Lys155Gln, Lys65Gln, Arg735Trp, Ser1619Arg), may also be associated with a high incidence of age-related macular degeneration in some ethnic groups. A protective haplotype of variants E318D and IVS10 in the C2 gene as well as L9H and R320 in the BF were associated with age-related macular degeneration but only in Caucasians. The genetic findings in age-related macular degeneration patients stress the importance of detailed phenotyping to identify age-related macular degeneration subtypes, which may be associated with the presence of different polymorphisms and various environmental risk factors in any population. Further studies may be helpful to improve the effectiveness of prophylaxis and therapeutic options in age

  20. Iron-induced Local Complement Component 3 (C3) Up-regulation via Non-canonical Transforming Growth Factor (TGF)-β Signaling in the Retinal Pigment Epithelium*

    PubMed Central

    Li, Yafeng; Song, Delu; Song, Ying; Zhao, Liangliang; Wolkow, Natalie; Tobias, John W.; Song, Wenchao; Dunaief, Joshua L.

    2015-01-01

    Dysregulation of iron homeostasis may be a pathogenic factor in age-related macular degeneration (AMD). Meanwhile, the formation of complement-containing deposits under the retinal pigment epithelial (RPE) cell layer is a pathognomonic feature of AMD. In this study, we investigated the molecular mechanisms by which complement component 3 (C3), a central protein in the complement cascade, is up-regulated by iron in RPE cells. Modulation of TGF-β signaling, involving ERK1/2, SMAD3, and CCAAT/enhancer-binding protein-δ, is responsible for iron-induced C3 expression. The differential effects of spatially distinct SMAD3 phosphorylation sites at the linker region and at the C terminus determined the up-regulation of C3. Pharmacologic inhibition of either ERK1/2 or SMAD3 phosphorylation decreased iron-induced C3 expression levels. Knockdown of SMAD3 blocked the iron-induced up-regulation and nuclear accumulation of CCAAT/enhancer-binding protein-δ, a transcription factor that has been shown previously to bind the basic leucine zipper 1 domain in the C3 promoter. We show herein that mutation of this domain reduced iron-induced C3 promoter activity. In vivo studies support our in vitro finding of iron-induced C3 up-regulation. Mice with a mosaic pattern of RPE-specific iron overload demonstrated co-localization of iron-induced ferritin and