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Sample records for macular pigment levels

  1. Aqueous Levels of Pigment Epithelium-Derived Factor and Macular Choroidal Thickness in High Myopia

    PubMed Central

    Chen, Wei; Guan, Yubo; He, Guanghui; Li, Zhiwei; Song, Hui; Xie, Shiyong; Han, Quanhong

    2015-01-01

    Purpose. To investigate the correlation between aqueous and serum levels of pigment epithelium-derived factor (PEDF) and macular choroidal thickness in high myopia patients, both with and without choroidal neovascularization (CNV). Methods. Serum and aqueous levels of PEDF were measured by enzyme-linked immunosorbent assay in 36 high myopia patients (36 eyes) with no CNV (non-CNV group), 14 high myopia patients (14 eyes) with CNV (CNV group), and 42 nonmyopia patients (42 eyes) (control group). Macular choroidal thickness was measured by enhanced-depth imaging optical coherence tomography. Results. Aqueous levels of PEDF were significantly higher in CNV group compared with non-CNV (P < 0.001) and control (P < 0.001) groups. Macular choroidal thicknesses were significantly decreased in the non-CNV and CNV groups compared with the control (P < 0.001) group. A statistically significant difference (P = 0.012) was found between the CNV and non-CNV groups. There was a positive correlation between aqueous PEDF and macular choroidal thickness in the non-CNV group (P = 0.005), but no correlation with the CNV group. No correlation between serum PEDF and macular choroidal thickness was detected in the three groups. Conclusion. Variations in aqueous PEDF levels coincide with changes in macular choroidal thickness in high myopia patients with no CNV, while no such relationship exists in high myopia patients with CNV. PMID:26491554

  2. Raman imaging of human macular pigments

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

    We have imaged the spatial distribution of macular carotenoid pigments (MPs) in the human retina, employing Raman spectroscopy. Using excised human eyecups as initial test samples 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 the molecules. Preliminary Raman images reveal significant differences in the MPs of different samples in regard to absolute levels as well as spatial variation. This technique holds promise as a method of rapid screening of MPs in large populations at risk for vision loss from age-related macular degeneration, a leading cause of blindness.

  3. Fast assessment of the central macular pigment density with natural pupil using the macular pigment reflectometer.

    PubMed

    van de Kraats, Jan; Berendschot, Tos T J M; Valen, Suze; van Norren, Dirk

    2006-01-01

    We built a new macular pigment reflectometer (MPR) for fast and objective measuring of the optical density of macular pigment in the human eye, using the undilated eye. The design is based on the spectral reflectance from a spot of white light at the fovea. To evaluate its performance, we measured the macular pigment of 20 healthy subjects, ages 18 to 79 years, under four conditions: (1) natural pupil in the dark, (2) natural pupil with dim room light, (3) dilated pupil in the dark, and for comparison with a different technique, (4) heterochromatic flicker photometry (HFP) in dim room light with natural pupil. Condition 1 was repeated in a subset of 10 subjects after an interval of at least 3 days. Data analysis with a model of reflectors and absorbers in the eye provided the density of the macular pigment in conditions 1 to 3. Dim room light and pupil dilatation had no influence on measured density. Mean within subjects variation was typically 7%. Mean difference between test and retest after at least 3 days was 1%. Correlation between MPR and HFP was r=0.56 (p=0.012). Mean within subjects variation with HFP was 19%. The new instrument holds promise for specific applications such as epidemiological research. PMID:17212554

  4. 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 ...

  5. Idiopathic eruptive macular pigmentation in a Chinese child

    PubMed Central

    Wei-Feng, Zha; Ai-E, Xu; Jun-Fan, Chen

    2015-01-01

    We present a case of a healthy 8-year-old boy who presented with disseminated asymptomatic brown macules on the face, neck, trunk, and proximal extremities for 3 months. Dermatologic examination revealed multiple, smooth, nonscaly, brown macules involving the face, neck, trunk, and proximal limbs. The Darier's sign was negative. Histopathologic study showed normal epidermis and basal membrane, and increasingly scattered melanophages in the papillary dermis. The final diagnosis was idiopathic eruptive macular pigmentation. PMID:26225334

  6. 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

  7. 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.

  8. The Value of Measurement of Macular Carotenoid Pigment Optical Densities and Distributions in Age-Related Macular Degeneration and Other Retinal Disorders

    PubMed Central

    Bernstein, Paul S.; Delori, François C.; Richer, Stuart; van Kuijk, Frederik J. M.; Wenzel, Adam J.

    2009-01-01

    There is increasing recognition that the optical and antioxidant properties of the xanthophyll carotenoids lutein and zeaxanthin play an important role in maintaining the health and function of the human macula. In this review article, we assess the value of non-invasive quantification of macular pigment levels and distributions to identify individuals potentially at risk for visual disability or catastrophic vision loss from age-related macular degeneration, and we consider the strengths and weaknesses of the diverse measurement methods currently available. PMID:19854211

  9. 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...

  10. Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment.

    PubMed

    Nolan, John M; Akkali, Mukunda C; Loughman, James; Howard, Alan N; Beatty, Stephen

    2012-08-01

    This study was designed to investigate the impact of macular carotenoid supplementation on the spatial profile of macular pigment (MP) in subjects where the profile does not exhibit the typical central peak (i.e. peaked MP at foveal epicentre). Thirty one healthy subjects with such atypical MP spatial profiles were assigned to one of three intervention groups: Group 1: (n = 10), 20 mg/day lutein (L), 2 mg/day zeaxanthin (Z); Group 2: (n = 10), 10 mg/day meso-zeaxanthin (MZ), 10 mg/day L, 2 mg/day Z; Group 3: (n = 10), 17 mg/day MZ, 3 mg/day L, 2 mg/day Z. Subjects were instructed to take one capsule daily over an 8-week period. MP at 0.25°, 0.5°, 1°, 1.75° and 3° was measured using customized-heterochromatic flicker photometry at baseline, four weeks and 8 weeks. Over the study period, we report no statistically significant increase in MP at any eccentricity in Group 1 (p > 0.05, for all eccentricities). There was a trend towards an increase in MP at all eccentricities in Group 2, with a significant increase found at 0.25° and 0.50° (p = 0.000 and p = 0.016, respectively). There was a statistically significant increase evident in MP at 0.25° in Group 3 (p = 0.005), but at no other eccentricity (p > 0.05, for all other). We report that the typical central peak of MP can be realised in subjects with atypical spatial profiles, following supplementation with a preparation containing all three macular carotenoids, but not with a supplement lacking MZ. The implications of our findings, in terms of visual performance and/or a (photo)-protective effect, warrant additional study. PMID:22652506

  11. Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin

    PubMed Central

    Bone, Richard A; Landrum, John T; Cao, Yisi; Howard, Alan N; Alvarez-Calderon, Francesca

    2007-01-01

    Background Age-related macular degeneration (AMD) is a disease with multiple risk factors, many of which appear to involve oxidative stress. Macular pigment, with its antioxidant and light-screening properties, is thought to be protective against AMD. A result has been the appearance of dietary supplements containing the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has been marketed containing, in addition, the third major carotenoid of the macular pigment, meso-zeaxanthin. The purpose of the study was to determine the effectiveness of such a supplement in raising macular pigment density in human subjects. Methods A 120 day supplementation study was conducted in which 10 subjects were given gel-caps that provided 20 mg/day of predominantly meso-zeaxanthin, with smaller amounts of lutein and zeaxanthin. A second group of 9 subjects were given gel caps containing a placebo for the same 120 day period. Prior to and during the supplementation period, blood serum samples were analyzed by high performance liquid chromatography for carotenoid content. Similarly, macular pigment optical density was measured by heterochromatic flicker photometry. Differences in response between the supplementation and placebo groups were tested for significance using a student's t-test. Results During supplementation with the carotenoids, blood samples revealed the presence of all three carotenoids. Macular pigment optical density, measured at 460 nm, rose at an average rate of 0.59 ± 0.79 milli-absorbance unit/day in the 10 supplemented subjects. This was significantly different from the placebo group (9 subjects) for whom the average rate was -0.17 ± 0.42 milli-absorbance units/day. Conclusion We have shown for the first time that meso-zeaxanthin is absorbed into the serum following ingestion. The data indicate that a supplement containing predominantly meso-zeaxanthin is generally effective at raising macular pigment density, and may turn out to be a useful addition to the defenses against AMD. PMID:17498306

  12. Temporal Visual Mechanisms May Mediate Compensation for Macular Pigment.

    PubMed

    Stringham, Nicole T; Stringham, James M

    2015-12-01

    Macular pigment (MP) is a pre-receptoral filter that is diet derived and deposited in relatively high optical density in the foveal region of the retina. Due to its yellow coloration, MP absorbs light of relatively short wavelengths, ranging from 400 nm to 520 nm. Despite the spectral and spatial nonuniformity imposed upon the sensory retina by MP, perception appears to be relatively uniform across the central visual field. MP therefore offers an opportunity to determine experimentally potential mechanisms responsible for mediating this uniformity. After assessing, in 14 subjects, MP's effects on the temporal sensitivity of both the short-wavelength- and middle-/long-wavelength-sensitive visual pathways, it appears that the visual system compensates for absorption of short-wavelength light by MP by slowing the sampling rate of short-wavelength cones and by increasing the processing speed of middle-/long-wavelength-sensitive cones. This mechanism could work via temporal summation or a temporal neural code, whereby slower response dynamics lead to amplification of relatively weak signals. PMID:26562864

  13. Macular pigment spatial distribution effects on glare disability

    PubMed Central

    Putnam, Christopher M.; Bassi, Carl J.

    2015-01-01

    Purpose This project explored the relationship of the macular pigment optical density (MPOD) spatial profile with measures of glare disability (GD) across the macula. Methods A novel device was used to measure MPOD across the central 16° of retina along four radii using customized heterochromatic flicker photometry (cHFP)at eccentricities of 0°, 2°, 4°, 6° and 8°. MPOD was measured as discrete and integrated values at all measured retinal loci. GD was calculated as a difference in contrast sensitivity (CS) between no glare and glare conditions using identical stimuli presented at the same eccentricities. GD was defined as [(CSNo Glare − CSGlare)/CSNo Glare] in order to isolate the glare attenuation effects of MPOD by controlling for CS variability among the subject sample. Correlations of the discrete and integrated MPOD with GD were compared. Results The cHFP identified reliable MPOD spatial distribution maps demonstrating a 1st-order exponential decay as a function of increasing eccentricity. There was a significant negative correlation between both measures of foveal MPOD and GD using 6 cycles per degree (cpd) and 9 cpd stimuli. Significant correlations were found between corresponding parafoveal MPOD measures and GD at 2 and 4° of eccentricity using 9 cpd stimuli with greater MPOD associated with less glare disability. Conclusions These results are consistent with the glare attenuation effects of MP at higher spatial frequencies and support the hypothesis that discrete and integrated measures of MPOD have similar correlations with glare attenuation effects across the macula. Additionally, peak foveal MPOD appears to influence GD across the macula. PMID:25697374

  14. The Macular Assessment Profile test - a new VDU-based technique for measuring the spatial distribution of the macular pigment, lens density and rapid flicker sensitivity.

    PubMed

    Barbur, J L; Konstantakopoulou, E; Rodriguez-Carmona, M; Harlow, J A; Robson, A G; Moreland, J D

    2010-09-01

    The measurement of macular pigment optical density (MPOD) in the eye is often carried out using optical techniques based on heterochromatic flicker photometry (HFP). These require the use of two spectrally-narrow beams, one at the wavelength of maximum absorption of the macular pigment (MP) and the other in the long wavelength region of the visible spectrum where MP absorption is negligible. A new technique for the measurement of MPOD spatial profiles has been developed by overcoming the current shortcomings associated with the use of visual displays. The new Macular Assessment Profile (MAP) test makes use of a 'notch' filter and a photometric model to measure and compute the peak MPOD value. Two other useful parameters are also computed from the same measurements. These describe the subject's sensitivity to rapid flicker and the absorption of blue light by the lens. MPOD profiles, lens density, rapid flicker sensitivity, and red/green (RG) and yellow/blue (YB) colour thresholds were measured in 54 normal subjects aged 18-61 years. The results confirm previous findings on ageing effects and demonstrate the complete absence of correlation between MPOD and the subject's YB chromatic thresholds. In contrast, RG chromatic sensitivity improves with higher levels of MPOD. PMID:20883330

  15. Absorption of the eye lens and macular pigment derived from the reflectance of cone photoreceptors

    NASA Astrophysics Data System (ADS)

    Zagers, Niels P. A.; van Norren, Dirk

    2004-12-01

    We measured the amplitude of the directional component of the bleached fundus reflectance, the so-called optical Stiles-Crawford effect, as a function of wavelength. The directional reflectance originates from within the outer segments of the photoreceptors. Thus only two anterior absorbers are of importance: macular pigment and the crystalline lens. Analysis of spectra obtained in pseudophakes established that the cone photoreceptors act as spectrally neutral reflectors. The reflectance spectra, expressed in density units, resembled the macular pigment density spectrum. Studying age effects in the lens of normal subjects resulted in a description of the optical density of the lens in terms of a ``young'' and an ``aged'' template. The young template represents the pigment O-β-glucoside of 3-hydroxykynurenine, which dominates the light absorption in young eyes and decreases with age. The aged template represents the pigments accumulating in the lens with age. The total optical density increased with age, but it was lower in the wavelength region 500-650 nm than was previously assumed on the basis of psychophysical studies. Analysis of the spectra also provided precise individual estimates of the optical density of macular pigment. Finally, we observed a decrease in the photoreceptor reflectivity with age, possibly reflecting a degradation of the photoreceptors.

  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. Lutein, zeaxanthin, macular pigment, and visual function in adult cystic fibrosis patients123

    PubMed Central

    Schupp, Christine; Olano-Martin, Estibaliz; Gerth, Christina; Morrissey, Brian M; Cross, Carroll E; Werner, John S

    2008-01-01

    Background Pancreatic insufficiency in cystic fibrosis (CF), even with replacement pancreatic enzyme therapy, is often associated with decreased carotenoid absorption. Because the macular pigment of the retina is largely derived from 2 carotenoids, lutein and zeaxanthin, the decreased serum concentrations seen in CF may have consequences for ocular and retinal health Objectives Our aims were to determine plasma carotenoid concentrations, determine absorption and distribution of macular pigment, and assess retinal health and visual function in CF patients. Design In 10 adult CF patients (ages 21–47 y) and 10 age- and sex-matched healthy control subjects, we measured macular pigment density in vivo, measured serum lutein and zeaxanthin concentrations, and comprehensively assessed visual performance (including contrast sensitivity, color discrimination, and retinal function) under conditions of daylight illumination. Results Serum lutein and zeaxanthin were significantly reduced (P< 0.005) in CF patients (x̄± SD:87 ± 36.1 and 27 ± 15.8 nmol/L, respectively) compared with control subjects (190 ± 72.1 and 75 ± 23.6 nmol/L, respectively). Although macular pigment optical density was significantly lower (P < 0.0001) in the CF group (0.24 ± 0.11) than in the control group (0.53 ± 0.12), no significant differences in visual function were observed. Conclusions Adults with CF have dramatically low serum and macular concentrations of carotenoids (lutein and zeaxanthin), but their ocular status and visual function are surprisingly good. The clinical implications of low plasma concentrations of carotenoids in CF are yet to be clarified. PMID:15159235

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

    PubMed

    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 lightinduced 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. PMID:25223707

  19. 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.

  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. PMID:26508289

  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. 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

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

    PubMed

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

    2016-01-01

    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

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

    NASA Astrophysics Data System (ADS)

    Smollon, William E., Jr.; 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.

  5. [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

  6. Black tongue secondary to bismuth subsalicylate: case report and review of exogenous causes of macular lingual pigmentation.

    PubMed

    Cohen, Philip R

    2009-12-01

    Macular pigmentation of the tongue can be acquired following exposure to exogenous agents. Black lingual hyperpigmentation was observed during the full body skin examination of a man with a history of recurrent metastatic malignant melanoma. His tongue spontaneously returned to its normal pink color later that day. Bismuth subsalicylate (Pepto-Bismol) was suspected as the pigment-inducing agent; subsequently, re-challange with the antacid confirmed it to be the cause of his acquired, albeit transient, black tongue. The ingestion of medications, including other antacids, analgesics, antidepressants, antihypertensives and several antimicrobials has been associated with the development of acquired macular lingual pigmentation. In addition, hyperpigmentation of the tongue has been observed following the deposition of amalgam and the injection of local anesthesia or doxorubicin or interferon alpha and ribavirin. Also, inhalation of heroin and methaqualone vapors or tobacco has resulted in lingual hyperpigmentation. All of the patients with acquired macular lingual hyperpigmentation had tongues with a smooth surface without enlargement of the filiform papillae. Many of the individuals with hyperpigmented tongue had either black or dark skin color. The onset of tongue pigmentation varied from less than one day to several years after initial exposure to the associated exogenous agent. The color of the tongue usually returned to normal after the pigment-inducing agent was discontinued. PMID:20027942

  7. 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

  8. Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration

    PubMed Central

    Nagineni, Chandrasekharam N.; Raju, Raghavan; Nagineni, Krishnasai K.; Kommineni, Vijay K.; Cherukuri, Aswini; Kutty, R. Krishnan; Hooks, John J.; Detrick, Barbara

    2014-01-01

    Age-related macular degeneration (AMD) is a sight threating retinal eye disease that affects millions of aging individuals world-wide. Choroid-retinal pigment epithelium (RPE)-neuroretina axis in the posterior compartment of the eye is the primary site of AMD pathology. There are compelling evidence to indicate association of vascular endothelial growth factors (VEGF) to AMD. Here, we report the inhibitory actions of resveratrol (RSV) on inflammatory cytokine, TGF-β and hypoxia induced VEGF secretion by human retinal pigment epithelial cells (HRPE). HRPE cultures prepared from aged human donor eyes were used for the studies in this report. HRPE secreted both VEGF-A and VEGF-C in small quantities constitutively. Stimulation with a mixture of inflammatory cytokines (IFN-γ, TNF-α, IL-1β), significantly increased the secretion of both VEGF-A and VEGF-C. RSV, in a dose dependent (10–50 uM) manner, suppressed VEGF-A and VEGF-C secretion induced by inflammatory cytokines significantly. RT-PCR analysis indicated that effects of RSV on VEGF secretion were possibly due to decreased mRNA levels. TGF-β and cobalt chloride (hypoxia mimic) also upregulated HRPE cell production of VEGF-A, and this was inhibited by RSV. In contrast, RSV had no effect on anti-angiogenic molecules, endostatin and pigment epithelial derived factor secretion. Studies using an in vitro scratch assay revealed that wound closure was also inhibited by RSV. These results demonstrate that RSV can suppress VEGF secretion induced by inflammatory cytokines, TGF-β and hypoxia. Under pathological conditions, over expression of VEGF is known to worsen AMD. Therefore, RSV may be useful as nutraceutical in controlling pathological choroidal neovascularization processes in AMD. PMID:24729934

  9. Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration.

    PubMed

    Nagineni, Chandrasekharam N; Raju, Raghavan; Nagineni, Krishnasai K; Kommineni, Vijay K; Cherukuri, Aswini; Kutty, R Krishnan; Hooks, John J; Detrick, Barbara

    2014-04-01

    Age-related macular degeneration (AMD) is a sight threating retinal eye disease that affects millions of aging individuals world-wide. Choroid-retinal pigment epithelium (RPE)-neuroretina axis in the posterior compartment of the eye is the primary site of AMD pathology. There are compelling evidence to indicate association of vascular endothelial growth factors (VEGF) to AMD. Here, we report the inhibitory actions of resveratrol (RSV) on inflammatory cytokine, TGF-β and hypoxia induced VEGF secretion by human retinal pigment epithelial cells (HRPE). HRPE cultures prepared from aged human donor eyes were used for the studies in this report. HRPE secreted both VEGF-A and VEGF-C in small quantities constitutively. Stimulation with a mixture of inflammatory cytokines (IFN-γ, TNF-α, IL-1β), significantly increased the secretion of both VEGF-A and VEGF-C. RSV, in a dose dependent (10-50 uM) manner, suppressed VEGF-A and VEGF-C secretion induced by inflammatory cytokines significantly. RT-PCR analysis indicated that effects of RSV on VEGF secretion were possibly due to decreased mRNA levels. TGF-β and cobalt chloride (hypoxia mimic) also upregulated HRPE cell production of VEGF-A, and this was inhibited by RSV. In contrast, RSV had no effect on anti-angiogenic molecules, endostatin and pigment epithelial derived factor secretion. Studies using an in vitro scratch assay revealed that wound closure was also inhibited by RSV. These results demonstrate that RSV can suppress VEGF secretion induced by inflammatory cytokines, TGF-β and hypoxia. Under pathological conditions, over expression of VEGF is known to worsen AMD. Therefore, RSV may be useful as nutraceutical in controlling pathological choroidal neovascularization processes in AMD. PMID:24729934

  10. Effects of Lutein and Docosahexaenoic Acid Supplementation on Macular Pigment Optical Density in a Randomized Controlled Trial

    PubMed Central

    García-Layana, Alfredo; Recalde, Sergio; Alamán, Angel Salinas; Robredo, Patricia Fernández

    2013-01-01

    We studied the macular pigment ocular density (MPOD) in patients with early age macular degeneration (AMD) before and 1 year after nutritional supplementation with lutein and docosahexaenoic acid (DHA). Forty-four patients with AMD were randomly divided into two groups that received placebo (n = 21) or a nutritional supplement (n = 23, 12 mg of lutein and 280 mg of DHA daily). Heterochromatic flicker photometry was used to determine the MPOD. At baseline, the MPOD in AMD patients with placebo was 0.286 ± 0.017 meanwhile in AMD patients with supplementation it was 0.291 ± 0.016. One year later, the mean MPOD had increased by 0.059 in the placebo group and by 0.162 in patients receiving lutein and DHA. This difference between groups was significant (p < 0.05). Lutein and DHA supplementation is effective in increasing the MPOD and may aid in prevention of age related macular degeneration. PMID:23434908

  11. 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.

  12. Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration.

    PubMed

    Ye, Fuxiang; Kaneko, Hiroki; Hayashi, Yumi; Takayama, Kei; Hwang, Shiang-Jyi; Nishizawa, Yuji; Kimoto, Reona; Nagasaka, Yosuke; Tsunekawa, Taichi; Matsuura, Toshiyuki; Yasukawa, Tsutomu; Kondo, Takaaki; Terasaki, Hiroko

    2016-05-01

    Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy-lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels. PMID:26923802

  13. Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

    PubMed Central

    Megyerdi, Sylvia; El-Shafey, Sally; Choksi, Karishma; Kaddour-Djebbar, Ismail; Sheibani, Nader; Hsu, Stephen

    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

  14. Changes in Select Redox Proteins of the Retinal Pigment Epithelium in Age-related Macular Degeneration

    PubMed Central

    DECANINI, ALEJANDRA; NORDGAARD, CURTIS L.; FENG, XIAO; FERRINGTON, DEBORAH A.; OLSEN, TIMOTHY W.

    2008-01-01

    PURPOSE To examine changes of select reduction-oxidation (redox) sensitive proteins from human donor retinal pigment epithelium (RPE) at four stages of age-related macular degeneration (AMD). DESIGN Experimental study. METHODS Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using the Minnesota Grading System (MGS) into four stages that correspond to stages defined by the age-related eye disease study (AREDS). Protein content in RPE homogenates was measured using Western immunoblotting with protein-specific antibodies. RESULTS The content of several antioxidant enzymes and specific proteins that facilitate refolding or degradation of oxidatively damaged proteins increased significantly in MGS stage 3. These proteins are involved in the primary (copper-zinc superoxide dismutase [CuZnSOD], manganese superoxide dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 90, and proteasome) defense against oxidative damage. Additionally, the insulin pro-survival receptor exhibited disease-related upregulation. CONCLUSIONS The pattern of protein changes identified in human donor tissue graded using the MGS support the role of oxidative mechanisms in the pathogenesis and progression of AMD. The MGS uses nearly identical clinical definitions and grading criteria of AMD that are used in the AREDS, so our results apply to clinical and epidemiologic studies using similar definitions. Results from our protein analysis of human donor tissue helps to explain altered oxidative stress regulation and cell-survival pathways that occur in progressive stages of AMD. PMID:17280640

  15. Subsurface femtosecond tissue alteration: selectively photobleaching macular degeneration pigments in near retinal contact.

    PubMed

    Manevitch, Zakhariya; Lewis, Aaron; Levy, Carol; Zeira, Evelyne; Banin, Eyal; Manevitch, Alexandra; Khatchatouriants, Artium; Pe'er, Jacob; Galun, Eithan; Hemo, Itzhak

    2012-06-14

    This paper uses advances in the ultrafast manipulation of light to address a general need in medicine for a clinical approach that can provide a solution to a variety of disorders requiring subsurface tissue manipulation with ultralow collateral damage. Examples are age-related macular degeneration (AMD), fungal infections, tumors surrounded by overlying tissue, cataracts, etc. Although lasers have revolutionized the use of light in clinical settings, most lasers employed in medicine cannot address such problems of depth-selective tissue manipulation. This arises from the fact that they are mostly based on one photon based laser tissue interactions that provide a cone of excitation where the energy density is sufficiently high to excite heat or fluorescence in the entire cone. Thus, it is difficult to excite a specific depth of a tissue without affecting the overlying surface. However, the advent of femtosecond (fs) lasers has caused a revolution in multiphoton microscopy (Zipfel et al. Nat. Biotechnol. 2003, 21, 1369-1377; Denk et al. Science 1990, 248, 73-76) and fabrication (Kawata et al. Nature 2001, 412, 697-698). With such lasers, the photon energy density is only high enough for multiphoton processes in the focal volume, and this opens a new direction to address subsurface tissue manipulation. Here we show in an AMD animal model, Ccr2 KO knockout mutant mice, noninvasive, selective fs two-photon photobleaching of pigments associated with AMD that accumulate under and in ultraclose proximity to the overlying retina. Pathological evidence is presented that indicates the lack of collateral damage to the overlying retina or other surrounding tissue. PMID:22482826

  16. 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 contrast sensitivity. Conclusions No statistically significant differences could be detected for MPOD levels and serum lutein concentrations between the two investigated lutein supplement formulations. Responses to lutein supplementation regarding MPOD levels and serum lutein concentrations varied between subjects. Subjects with lower MPOD levels at baseline responded well to lutein supplementation. However, since the number of subjects was low, a further study with more subjects is needed to prove that subjects with low MPOD levels will benefit from lutein supplementation. Trial Registration UMIN-CTR UMIN000004593 PMID:26451726

  17. 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

  18. 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 and integrated measures of MPOD were similar in regards to their association with glare attenuation effects across the macula. Quartile analysis of the highest and lowest peak foveal MPOD values demonstrated significant differences in intraocular scatter which indicate MPOD may minimize scattered intraocular short-wavelength light.

  19. Vitreous estrogen levels in patients with an idiopathic macular hole

    PubMed Central

    Inokuchi, Naoki; Ikeda, Tsunehiko; Nakamura, Kimitoshi; Morishita, Seita; Fukumoto, Masanori; Kida, Teruyo; Oku, Hidehiro

    2015-01-01

    Purpose Estrogen, a female hormone, activates collagenase and might be associated with the pathogenesis of vitreoretinal collagen fiber disease. The purpose of the present study was to investigate the vitreous levels of estrone (E1) and estradiol (E2) in subjects with an idiopathic macular hole (IMH). Methods Vitreous samples were obtained from ten female patients with an IMH and from nine female patients with other retinal diseases (six with rhegmatogenous retinal detachment and three with age-related macular degeneration) as a control at the time of vitreous surgery. E1 and E2 levels in the vitreous samples were then determined using the Coat-A-Count® Estradiol Radioimmunoassay (RIA) Kit and the DSL-70 Estrone RIA Kit, respectively. Results The mean vitreous levels of E1 and E2 in the subjects with IMH were 1.83±2.00 pg/mL and 7.03±2.97 pg/mL, respectively, whereas in the control subjects they were 2.42±1.25 pg/mL and 4.90±2.90 pg/mL, respectively. Thus, the vitreous E2 levels in the subjects with IMH were significantly higher than in the controls (P<0.05). Conclusion The findings of this study suggest that E2 might be associated with the pathogenesis of IMH, but further investigation is needed to elucidate that association. PMID:25848205

  20. NUTRITIONAL MANIPULATION OF PRIMATE RETINA, I: EFFECTS OF LUTEIN OR ZEAXANTHIN SUPPLEMENTS ON SERUM AND MACULAR PIGMENT IN XANTHOPHYLL-FREE RHESUS MONKEYS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The xanthophylls lutein (L) and zeaxanthin (Z) are the primary components of macular pigment and may protect the macula from age-related degeneration (AMD). Rhesus monkeys represent a potential animal model to study mechanisms of protection from AMD. In this study, L or Z was fed to rhesus monkeys r...

  1. Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration

    PubMed Central

    Sinha, Debasish; Blasiak, Janusz; Kauppinen, Anu; Veréb, Zoltán; Salminen, Antero; Boulton, Michael E.; Petrovski, Goran

    2013-01-01

    Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the retinal pigment epithelium (RPE), is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. To date, there is increasing evidence that constant oxidative stress impairs autophagy and heterophagy, as well as increases protein aggregation and causes inflammasome activation leading to the pathological phenotype of AMD. This review ties together these crucial pathological topics and reflects upon autophagy as a potential therapeutic target in AMD. PMID:23590900

  2. 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

  3. Treatment of Macular Degeneration Using Embryonic Stem Cell-Derived Retinal Pigment Epithelium: Preliminary Results in Asian Patients

    PubMed Central

    Song, WonKyung; Park, Kyung-Mi; Kim, Hyun-Ju; Lee, JaeHo; Choi, Jinjung; Chong, SoYoung; Shim, SungHan; DelPriore, LucianV.; Lanza, Robert

    2015-01-01

    Summary 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 919 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. PMID:25937371

  4. 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 studies. PMID:25813989

  5. 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) raising serum HDL-C without an adverse affect on serum LDL-C and TC:HDL-C ratio. Increased cholesterol, lutein and zeaxanthin intake from the 2 and 4 egg yolk interventions did not decrease the absorption of other carotenoids, such as alpha-cryptoxanthin, beta-cryptoxanthin, lycopene, alpha-carotene and beta-carotene, tocopherols and retinol from the diet. An unexpected increase was observed in serum alpha-cryptoxanthin and gamma-tocopherol concentrations during the 4 egg yolk phase, these carotenoids are normally present in low concentrations in serum. Lipoprotein distribution of carotenoids and tocopherols was also not affected by the increased egg consumption. In the pursuit of designing a highly bioavailable matrix for lutein/zeaxanthin, similar to the egg yolk micellar matrix, nanoemulsion formulations of lutein were developed using the MicrofluidizerRTM Processor technology. Lutein nanoemulsions are O/W emulsions of lutein which have particle sizes in the nanometer range (≤ 200 nm). Lutein consumed orally as a nanoemulsion was shown to have significantly greater bioavailability than lutein supplement-pills in pilot-scale clinical studies described here. However, lutein nanoemulsions did not raise plasma lutein concentrations to the same extent as egg yolks in a study performed on BALB/c mice. Formation of mixed micelles in the intestinal lumen during digestion and uptake of these micelles by enterocytes are crucial steps that dictate bioavailability i.e. the proportion of ingested lutein/carotenoid that enters the blood circulation and accumulates in the peripheral tissues such as the macula. In-vitro stomach and intestinal digestion experiments showed lutein nanoemulsions have significantly greater micellarization efficiency compared to egg yolks. Nanoemulsions with a phospholipid (PL) emulsifier containing 80% phosphatidyl choline (PC) or Polysorbate 80 as the emulsifier had better ability to form micelles during the intestinal digestion phase compared to a PL emulsifier with only 45% PC content. The micellar matrix coupled with nanometer sized particles thus favored micelle formation even in the absence of additional fat. Despite the greater micellar efficiency with the nanoemulsions, significantly greater lutein uptake by Caco-2 cells was observed from egg yolk micelles compared to nanoemulsion micelles. These findings suggest that even though micellarization efficiency was higher with the nanoemulsions, the fat content of the micelles may play a role in cellular uptake of lutein. The lutein nanoemulsion delivery system could be improved by increasing the triglyceride content and modifying the phospholipid emulsifier (may be using emulsifiers with higher lysoPC content), in such a way so as to increase cellular uptake of lutein without increasing the particle size. Thus, nanometer particle size alone does not necessarily imply greater bioavailability in the case of lutein. The matrix of delivery of lutein is suggested to be of equal importance. With improved bioavailability nanoemulsions of lutein and zeaxanthin added to a beverage would be easier for an older adult population to consume as opposed to large supplement-pills. Nanometer particle size in combination with an ideal matrix may also avoid the need to consume pharmacological doses of these carotenoids to achieve significant health benefits.

  6. 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 degeneration. PMID:26517551

  7. Effectiveness of Intravitreal Injection of Ranibizumab for Neovascular Age-Related Macular Degeneration with Serous Pigment Epithelial Detachment

    PubMed Central

    Zhao, Chun; Zhang, Zhen; Chen, Lei; Wang, Fang; Xu, Ding

    2016-01-01

    Background We sought to observe the effectiveness of intravitreal injection of ranibizumab in treating neovascular age-related macular degeneration (nAMD) with serous pigment epithelial detachment (sPED). Material/Methods A retrospective, noncomparative case series was performed. Twenty-3 eyes of 23 patients with sPED secondary to nAMD who had received intravitreal injections of ranibizumab were included in this study. All patients underwent best-corrected visual acuity (BCVA), synchronous fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) examinations. All patients were treated with pro re nata intravitreal injections after 3 loading doses of ranibizumab and were followed up for 12 months. The differences in the BCVAs, maximum PED heights, PED volumes and CFTs of the affected eyes were compared between the baseline and last visit. Results Twelve months after the first injection, improved visual acuity was observed in 16 of the 23 eyes. 4 eyes exhibited stable visual acuity, and 3 eyes exhibited impaired visual acuity. The mean post-injection logMAR BCVA was 0.58±0.05, which was much better than that at baseline (0.76±0.08; t=1.751, P=0.0869). The mean maximum PED height at baseline was 350.17±35.73μm and it was decreased to 238.87±36.87μm (t=2.192, P=0.0337) at the last visit. The mean PED volume after injection was 0.34±0.1 mm3, which was significantly decreased compared with that at baseline (0.81±0.21 mm3; t=2.021, P=0.0494).The mean CFT decreased, but this difference was not statistically significant (t=1.003, P=0.3211). None of the patients exhibited endophthalmitis, uveitis or RPE tears. Conclusions Intravitreal injection of ranibizumab for the treatment of neovascular age-related macular degeneration with serous pigment epithelial detachment safely and effectively improved the patients’ visual acuities and decreased their PED heights volumes. PMID:26972376

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

    PubMed Central

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

    2008-01-01

    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 (Nt-BHA), 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. PMID:17656467

  9. Lipofuscin Redistribution and Loss Accompanied by Cytoskeletal Stress in Retinal Pigment Epithelium of Eyes With Age-Related Macular Degeneration

    PubMed Central

    Ach, Thomas; Tolstik, Elen; Messinger, Jeffrey D.; Zarubina, Anna V.; Heintzmann, Rainer; Curcio, Christine A.

    2015-01-01

    Purpose. Lipofuscin (LF) and melanolipofuscin (MLF) of the retinal pigment epithelium (RPE) are the principal sources of autofluorescence (AF) signals in clinical fundus–AF imaging. Few details about the subcellular distribution of AF organelles in AMD are available. We describe the impact of aging and AMD on RPE morphology revealed by the distribution of AF LF/MLF granules and actin cytoskeleton in human tissues. Methods. Thirty-five RPE-Bruch's membrane flatmounts from 35 donors were prepared (postmortem: ≤4 hours). Ex vivo fundus examination at the time of accession revealed either absence of chorioretinal pathologies (10 tissues; mean age: 83.0 ± 2.6 years) or stages of AMD (25 tissues; 85.0 ± 5.8 years): early AMD, geographic atrophy, and late exudative AMD. Retinal pigment epithelium cytoskeleton was labeled with AlexaFluor647-Phalloidin. Tissues were imaged on a spinning-disk fluorescence microscope and a high-resolution structured illumination microscope. Results. Age-related macular degeneration impacts individual RPE cells by (1) lipofuscin redistribution by (i) degranulation (granule-by-granule loss) and/or (ii) aggregation and apparent shedding into the extracellular space; (2) enlarged RPE cell area and conversion from convex to irregular and sometimes concave polygons; and (3) cytoskeleton derangement including separations and breaks around subretinal deposits, thickening, and stress fibers. Conclusions. We report an extensive and systematic en face analysis of LF/MLF-AF in AMD eyes. Redistribution and loss of AF granules are among the earliest AMD changes and could reduce fundus AF signal attributable to RPE at these locations. Data can enhance the interpretation of clinical fundus–AF and provide a basis for future quantitative studies. PMID:25758814

  10. 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. PMID:24114020

  11. 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.

  12. Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration.

    PubMed

    Ferrington, Deborah A; Sinha, Debasish; Kaarniranta, Kai

    2016-03-01

    Maintenance of protein homeostasis, also referred to as "Proteostasis", integrates multiple pathways that regulate protein synthesis, folding, translocation, and degradation. Failure in proteostasis may be one of the underlying mechanisms responsible for the cascade of events leading to age-related macular degeneration (AMD). This review covers the major degradative pathways (ubiquitin-proteasome and lysosomal involvement in phagocytosis and autophagy) in the retinal pigment epithelium (RPE) and summarizes evidence of their involvement in AMD. Degradation of damaged and misfolded proteins via the proteasome occurs in coordination with heat shock proteins. Evidence of increased content of proteasome and heat shock proteins in retinas from human donors with AMD is consistent with increased oxidative stress and extensive protein damage with AMD. Phagocytosis and autophagy share key molecules in phagosome maturation as well as degradation of their cargo following fusion with lysosomes. Phagocytosis and degradation of photoreceptor outer segments ensures functional integrity of the neural retina. Autophagy rids the cell of toxic protein aggregates and defective mitochondria. Evidence suggesting a decline in autophagic flux includes the accumulation of autophagic substrates and damaged mitochondria in RPE from AMD donors. An age-related decrease in lysosomal enzymatic activity inhibits autophagic clearance of outer segments, mitochondria, and protein aggregates, thereby accelerating the accumulation of lipofuscin. This cumulative damage over a person's lifetime tips the balance in RPE from a state of para-inflammation, which strives to restore cell homeostasis, to the chronic inflammation associated with AMD. PMID:26344735

  13. Macular telangiectasia type 2

    PubMed Central

    Issa, Peter Charbel; Gillies, Mark C.; Chew, Emily Y.; Bird, Alan C.; Heeren, Tjebo F.C.; Peto, Tunde; Holz, Frank G.; Scholl, Hendrik P.N.

    2013-01-01

    Macular telangiectasia type 2 is a bilateral disease of unknown cause with characteristic alterations of the macular capillary network and neurosensory atrophy. Its prevalence may be underestimated and has recently been shown to be as high as 0.1% in persons 40 years and older. Biomicroscopy may show reduced retinal transparency, crystalline deposits, mildly ectatic capillaries, blunted venules, retinal pigment plaques, foveal atrophy, and neovascular complexes. Fluorescein angiography shows telangiectatic capillaries predominantly temporal to the foveola in the early phase and a diffuse hyperfluorescence in the late phase. High-resolution optical coherence tomography (OCT) may reveal disruption of the photoreceptor inner segment–outer segment border, hyporeflective cavities at the level of the inner or outer retina, and atrophy of the retina in later stages. Macular telangiectasia type 2 shows a unique depletion of the macular pigment in the central retina and recent therapeutic trials showed that such depleted areas cannot re-accumulate lutein and zeaxanthin after oral supplementation. There have been various therapeutic approaches with limited or no efficacy. Recent clinical trials with compounds that block vascular endothelial growth factor (VEGF) have established the role of VEGF in the pathophysiology of the disease, but have not shown significant efficacy, at least for the nonneovascular disease stages. Recent progress in structure–function correlation may help to develop surrogate outcome measures for future clinical trials. In this review article, we summarize the current knowledge on macular telangiectasia type 2, including the epidemiology, the genetics, the clinical findings, the staging and the differential diagnosis of the disease. Findings using retinal imaging are discussed, including fluorescein angiography, OCT, adaptive optics imaging, confocal scanning laser ophthalmoscopy, and fundus autofluorescence, as are the findings using visual function testing including visual acuity and fundus-controlled microperimetry. We provide an overview of the therapeutic approaches for both non-neovascular and neovascular disease stages and provide a perspective of future directions including animal models and potential therapeutic approaches. PMID:23219692

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

    PubMed

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

    2015-10-01

    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

  15. Macular Hole

    MedlinePlus

    ... Hole > Facts About Macular Hole Facts About Macular Hole Listen This information was developed by the National ... the best person to answer specific questions. Macular Hole Defined What is a macular hole? A macular ...

  16. The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress

    PubMed Central

    Chang, Yun-Ching; Chang, Wei-Chao; Hung, Kuo-Hsuan; Yang, Der-Ming; Cheng, Yung-Hsin; Liao, Yi-Wen; Woung, Lin-Chung; Tsai, Ching-Yao; Hsu, Chih-Chien; Lin, Tai-Chi; Liu, Jorn-Hon; Chiou, Shih-Hwa; Peng, Chi-Hsien; Chen, Shih-Jen

    2014-01-01

    Age-related macular degeneration (AMD) is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE) cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs) via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2, and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient-derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress. PMID:25136316

  17. The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress.

    PubMed

    Chang, Yun-Ching; Chang, Wei-Chao; Hung, Kuo-Hsuan; Yang, Der-Ming; Cheng, Yung-Hsin; Liao, Yi-Wen; Woung, Lin-Chung; Tsai, Ching-Yao; Hsu, Chih-Chien; Lin, Tai-Chi; Liu, Jorn-Hon; Chiou, Shih-Hwa; Peng, Chi-Hsien; Chen, Shih-Jen

    2014-01-01

    Age-related macular degeneration (AMD) is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE) cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs) via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2, and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient-derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress. PMID:25136316

  18. 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.

  19. 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

    2015-01-01

    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 secretion of inflammatory cytokines and VEGFA. PMID:26561782

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

    PubMed Central

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

    2015-01-01

    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 secretion of inflammatory cytokines and VEGFA. PMID:26561782

  1. Macular Pucker

    MedlinePlus

    ... Is a macular pucker similar to a macular hole? Although both have similar symptoms - distorted and blurred vision - macular pucker and a macular hole are different conditions. They both result from tugging ...

  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. Macular auto-fluorescence is a follow-up parameter for cystoids macular edema.

    PubMed

    Zhang, XinYuan; Gong, XiaoHong; Wang, YanHong; Wang, NingLi

    2015-08-01

    This study aimed to evaluate if macular autofluorescence (MAF) is a valuable, non-invasive follow-up parameter for cystoid macular edema. A total of 71 eyes (71 cases) with cystoid macular edema (CME) were included in the study. Macular pigment (MP) was evaluated using HRA2 (infrared) IF and FA models. The density of MP was graded into three categories: without, partial, and normal amount of MP. A comparison was made between the baseline (before the first administration) level and at the fourth month, following three consecutive intravitreal lucentis injections every month. The morphology and distribution of MAF, and the density and distribution of MP were regarded as the main outcome measures. At the baseline visit, all eyes with CME had petaloid/irregular-shaped MAF in the macular area (100%). No MAF was detected in the control eyes (0). There was significant difference in MAF between the CME and normal groups (P=0.000). At the fourth monthly visit, normal levels of MP density without MAF was detected in 68 eyes (95.8%) with the best corrected spectacular visual acuity increasing to at least 1 line accordingly. We conclude that macular MAF can be used as a follow-up parameter for patients with CME. MP and MAF can indirectly reflect the fovea cone function. PMID:26187408

  4. Macular dystrophy associated with the mitochondrial DNA A3243G mutation: pericentral pigment deposits or atrophy? Report of two cases and review of the literature

    PubMed Central

    2014-01-01

    Background The A3243G point mutation in mitochondrial DNA (mtDNA) is associated with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and MIDD syndromes (maternally inherited diabetes and deafness). Both MELAS and MIDD patients can present with visual symptoms due to a retinopathy, sometimes before the genetic diagnosis is made. Case presentation Patient 1: 46 year-old woman with diabetes mellitus and hearing loss was referred for an unspecified maculopathy detected during screening evaluation for diabetic retinopathy. Visual acuity was 20/20 in both eyes. Fundus examination showed bilateral macular and peripapillary hyperpigmented/depigmented areas. Patient 2: 45 year-old woman was referred for recent vision loss in her left eye. History was remarkable for chronic fatigue, migraine and diffuse muscular pain. Visual acuity was 20/20 in her right eye and 20/30 in her left eye. Fundus exhibited several nummular perifoveal islands of retinal pigment epithelium atrophy and adjacent pale deposits in both eyes. Retinal anatomy was investigated with autofluorescence, retinal angiography and optical coherence tomography. Retinal function was assessed with automated static perimetry, full-field and multifocal electroretinography and electro-oculography. Genetic testing of mtDNA identified a point mutation at the locus 3243. Conclusion Observation of RPE abnormalities in the context of suggestive systemic findings should prompt mtDNA testing. PMID:24906873

  5. Automated 3-D retinal layer segmentation of macular optical coherence tomography images with serous pigment epithelial detachments.

    PubMed

    Shi, Fei; Chen, Xinjian; Zhao, Heming; Zhu, Weifang; Xiang, Dehui; Gao, Enting; Sonka, Milan; Chen, Haoyu

    2015-02-01

    Automated retinal layer segmentation of optical coherence tomography (OCT) images has been successful for normal eyes but becomes challenging for eyes with retinal diseases if the retinal morphology experiences critical changes. We propose a method to automatically segment the retinal layers in 3-D OCT data with serous retinal pigment epithelial detachments (PED), which is a prominent feature of many chorioretinal disease processes. The proposed framework consists of the following steps: fast denoising and B-scan alignment, multi-resolution graph search based surface detection, PED region detection and surface correction above the PED region. The proposed technique was evaluated on a dataset with OCT images from 20 subjects diagnosed with PED. The experimental results showed the following. 1) The overall mean unsigned border positioning error for layer segmentation is 7.87±3.36 μm , and is comparable to the mean inter-observer variability ( 7.81±2.56 μm). 2) The true positive volume fraction (TPVF), false positive volume fraction (FPVF) and positive predicative value (PPV) for PED volume segmentation are 87.1%, 0.37%, and 81.2%, respectively. 3) The average running time is 220 s for OCT data of 512 × 64 × 480 voxels. PMID:25265605

  6. Association between Blood Lead Levels and Age-Related Macular Degeneration

    PubMed Central

    Hwang, Ho Sik; Lee, Seung Bum; Jee, Donghyun

    2015-01-01

    Purpose To investigate the association between blood lead levels and prevalence of age-related macular degeneration (AMD). Methods A nationwide population-based cross-sectional study included 4,933 subjects aged over 40 years who participated in the 2008–2012 Korean National Health and Nutrition Examination Survey, and for whom fundus photographs were available. All participants underwent a standardized interview, evaluation of blood lead concentration, and a comprehensive ophthalmic examination. Digital fundus photographs (45°) were taken of both eyes under physiological mydriasis. All fundus photographs were graded using an international classification and grading system. Results Mean blood lead levels were 3.15 μg/dL in men and 2.27 μg/dL in women (P < 0.001). After adjusting for potential confounders including age, gender, smoking status, total cholesterol levels, triglyceride levels, heart problems and strokes, the adjusted odds ratio (OR) in women for any AMD was 1.86 (95% Confidence Interval [CI], 1.03–3.36) and for early AMD was 1.92 (95% CI, 1.06–3.48), for those in the highest quintile of lead level compared with the lowest quintile. In men, however, blood lead level was not significantly associated with AMD. Conclusions Blood lead levels were higher in men, but were only associated with AMD in women. Increased levels of blood lead may be involved in the pathogenesis of AMD development in women. PMID:26252225

  7. Macular degeneration

    MedlinePlus Videos and Cool Tools

    ... 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.

  8. Macular changes resulting from papilloedema.

    PubMed Central

    Morris, A T; Sanders, M D

    1980-01-01

    Six cases are presented with macular changes in association with papilloedema; 4 suffered permanent visual loss. The present paper emphasises this previously infrequent finding and discusses the haemodynamic and mechanical factors responsible. The macular changes consisted of haemorrhages situated in front, within, or behind the retina, and occasionally the results of neovascular membrane formation produced secondary visual loss. Changes in the pigment epithelium were seen in 3 cases associated with choroidal folds. Macular stars rarely produce visual loss. Recognition of these changes is important in the assessment of the visual loss in papilloedema. Images PMID:7387954

  9. Serum levels of lipid metabolites in age-related macular degeneration.

    PubMed

    Orban, Tivadar; Johnson, William M; Dong, Zhiqian; Maeda, Tadao; Maeda, Akiko; Sakai, Tsutomu; Tsuneoka, Hiroshi; Mieyal, John J; Palczewski, Krzysztof

    2015-11-01

    Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4(-/-)Rdh8(-/-) mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4(-/-)Rdh8(-/-) mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala(69)→Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD. PMID:26187344

  10. Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

    PubMed Central

    Örnek, Nurgül; Örnek, Kemal; Aydin, Süleyman; Yilmaz, Musa; Ölmez, Yaşar

    2016-01-01

    AIM To investigate the serum levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and adropin in age-related macular degeneration (AMD) patients. METHODS Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group. Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups. RESULTS AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness (P =0.01, 0.047, 0.025 and <0.001, respectively). Serum VEGFR-2 level revealed a significant decrease in AMD patients compared to controls (26.48±6.44 vs 30.42±7.92 ng/mL, P<0.001). There was an insignificant increase in serum adropin level in AMD patients (6.17±3.19 vs 5.79±2.71 ng/mL, P=0.4). Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness (r=-0.226, P=0.025) and a significant positive correlation with subfoveal choroidal thickness (r=0.2, P=0.048). CONCLUSION The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD. PMID:27162728

  11. 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 Central

    van der Made, Sanne M.; Kelly, Elton R.; Kijlstra, Aize; Plat, Jogchum

    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. PMID:27064326

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

    PubMed

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

    2016-04-01

    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 p16(INK4a) and p21(Waf-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 with cigarette smoking. PMID:26654980

  13. 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 with cigarette smoking. PMID:26654980

  14. Concentration levels and congener profiles of polychlorinated biphenyls, pentachlorobenzene, and hexachlorobenzene in commercial pigments.

    PubMed

    Anezaki, Katsunori; Nakano, Takeshi

    2014-01-01

    The concentration levels and congener profiles of polychlorinated biphenyls (PCBs), pentachlorobenzene (PeCBz), and hexachlorobenzene (HxCBz) were assessed in commercially available organic pigments. Among the azo-type pigments tested, PCB-11, which is synthesized from 3,3'-dichlorobendizine, and PCB-52, which is synthesized from 2,2',5,5'-tetrachlorobendizine, were the major congeners detected. It is speculated that these were byproducts of chlorobendizine, which has a very similar structure. The total PCB concentrations in this type of pigment ranged from 0.0070 to 740 mg/kg. Among the phthalocyanine-type pigments, highly chlorinated PCBs, mainly composed of PCB-209, PeCBz, and HxCBz were detected. Their concentration levels ranged from 0.011 to 2.5 mg/kg, 0.0035 to 8.4 mg/kg, and 0.027 to 75 mg/kg, respectively. It is suggested that PeCBz and HxCBz were formed as byproducts and converted into PCBs at the time of synthesizing the phthalocyanine green. For the polycyclic-type pigments that were assessed, a distinctive PCB congener profile was detected that suggested an impact of their raw materials and the organic solvent used in the pigment synthesis. PCB pollution from PCB-11, PCB-52, and PCB-209 pigments is of particular concern; therefore, the monthly variations in atmospheric concentrations of these pollutants were measured in an urban area (Sapporo city) and an industrial area (Muroran city). The study detected a certain level of PCB-11, which is not included in PCB technical mixtures, and revealed continuing PCB pollution originating from pigments in the ambient air. PMID:23852585

  15. Macular Degeneration

    MedlinePlus

    ... is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease causes vision loss. Treatment can slow vision loss. It does not restore ...

  16. 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

    Convergencethe independent evolution of the same trait by two or more taxahas 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

  17. 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...

  18. Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years.

    PubMed

    Schwartz, Steven D; Tan, Gavin; Hosseini, Hamid; Nagiel, Aaron

    2016-04-01

    Advanced macular degeneration is an important cause of vision loss in the United States with over 2 million people affected by the disease. Despite substantial progress in the development of new therapies for wet AMD, the severe visual impairment associated with geographic atrophy in dry AMD or Stargardt disease remains untreatable. Recently, two phase I/II studies involving 18 patients with these diseases have demonstrated that it is possible to safely implant human embryonic stem cell-derived RPE (hESC-RPE) in an attempt to rescue photoreceptors and visual function. The anatomical and functional results are encouraging, with more than half of treated patients experiencing sustained improvements in visual acuity and demonstrating evidence of possible cellular engraftment. However, any conclusions remain tempered by the relatively short follow-up time, lack of a formal control group, poor initial visual acuity, and small number of patients. Aside from an instance of postoperative infectious endophthalmitis, no adverse events related to the cell therapy, such as hyperproliferation, tumorigenicity, or rejection-related inflammation were noted in this initial cohort of 18 patients. These first-in-human safety studies have opened the door to future studies enrolling patients with less advanced disease, treating other diseases that result in RPE loss, employing shorter immunosuppressive regimens, and using alternative strategies for RPE transplantation such as sheets of cells with or without scaffolding to mimic Bruch's membrane. The ultimate goal of these initial safety studies is to promote continued translation of complex biological therapies into meaningful treatment strategies that may address unmet medical needs. PMID:27116660

  19. 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

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

    PubMed Central

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

    2014-01-01

    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

  1. 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 ...

  2. 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

  3. Aqueous interleukin-6 levels are superior to vascular endothelial growth factor in predicting therapeutic response to bevacizumab in age-related macular degeneration.

    PubMed

    Chalam, Kakarla V; Grover, Sandeep; Sambhav, Kumar; Balaiya, Sankarathi; Murthy, Ravi K

    2014-01-01

    Objective. To prospectively evaluate the effect of intravitreal bevacizumab on aqueous levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with exudative age-related macular degeneration (AMD) and correlate clinical outcomes with cytokine levels. Methods. 30 eyes of 30 patients with exudative AMD underwent intravitreal injection of bevacizumab three times at monthly intervals. The aqueous samples prior to the 1st injection (baseline) and 3rd injection were analyzed for VEGF and IL-6 levels. Subjects were subgrouped based upon change in the central subfield (CSF) macular thickness on SD-OCT at 8 weeks. Group 1 included patients (n = 14) with a decrease in CSF thickness greater than 10% from the baseline (improved group). Group 2 included patients (n = 16) who had a decrease in CSF thickness 10% or less (treatment-resistant). Results. In subgroup analysis, in both groups 1 and 2 patients, compared to aqueous VEGF, aqueous IL-6 levels showed a better correlation with CSF thickness on SD-OCT (r = 0.72 and 0.71, resp.). Conclusions. Aqueous IL-6 may be an important marker of treatment response or resistance in wet macular degeneration. Future therapeutic strategies may include targeted treatment against both VEGF and IL-6, in patients who do not respond to anti-VEGF treatment alone. PMID:25110587

  4. Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex

    PubMed Central

    Bhutto, Imran; Lutty, Gerard

    2012-01-01

    There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch’s membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85–90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10–15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex. PMID:22542780

  5. Omega-3 Supplementation Combined With Anti–Vascular Endothelial Growth Factor Lowers Vitreal Levels of Vascular Endothelial Growth Factor in Wet Age-Related Macular Degeneration

    PubMed Central

    REZENDE, FLAVIO A.; LAPALME, ERIC; QIAN, CYNTHIA X.; SMITH, LOIS E.; SANGIOVANNI, JOHN PAUL; SAPIEHA, PRZEMYSLAW

    2015-01-01

    PURPOSE To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A (VEGF-A) levels in patients with exudative age-related macular degeneration (wet AMD) receiving intravitreal anti-VEGF treatment. DESIGN Prospective, randomized, open-label, single-center, clinical trial, consecutive interventional case series. METHODS The study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole. Twenty wet AMD patients being treated with anti-VEGF were randomized to daily supplementation of antioxidants, zinc, and carotenoids with omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid; group 1, n = 10) or without omega-3 fatty acids (group 2, n = 10). They were compared with an anti-VEGF treatment-naïve wet AMD group (group 3, n = 10) and an epiretinal membrane or macular hole group (group 4, n = 10). Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness. Patients with new submacular hemorrhage or any other treatment within 3 months were excluded. Final analyses included 9, 6, 7, and 8 patients in groups 1 through 4, respectively. RESULTS Patients receiving omega-3s (group 1) had significantly lower levels of vitreal VEGF-A (141.11 ± 61.89 pg/mL) when compared with group 2 (626.09 ± 279.27 pg/mL; P = .036) and group 3 (735.48 ± 216.43 pg/mL; P = .013), but similar levels to group 4 (235.81 ± 33.99 pg/mL; P=.215). All groups showed similar values for plasma VEGF-A and central foveal thickness measurements. CONCLUSIONS This study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients. PMID:25089351

  6. 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. PMID:23913900

  7. 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 ...

  8. 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.…

  9. Skin pigmentation, sun exposure and vitamin D levels in children of the Avon Longitudinal Study of Parents and Children

    PubMed Central

    2014-01-01

    Background It has been hypothesised that light skin pigmentation has arisen to ensure adequate levels of vitamin D as human populations moved out of Africa and into higher latitudes. Vitamin D, which is primarily obtained through exposure to sunlight (specifically ultraviolet radiation B (UVR-B)), has been inversely associated with several complex diseases. Greater sun exposure, on the other hand, is a well-known cause of skin cancer. The potential of UVR to be beneficial for some health outcomes but detrimental for others has prompted a public health debate on how to balance the positive and negative consequences of sun exposure. In this study we aimed to determine the validity of the evolutionary hypothesis linking lighter skin with higher vitamin D concentrations in a European population. Additionally, we aimed to examine the influence of pigmentation on personal behaviour towards sunlight exposure and the effects of this behaviour on vitamin D. Methods We combined genetic variants strongly associated with skin colour, tanning or freckling to create genetic scores for each of these phenotypes. We examined the association of the scores with pigmentary traits, sun exposure and serum 25-hydroxyvitamin D (25(OH)D) levels among children of the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 661 to 5649). Results We found that fairer-skinned children, i.e. those with higher pigmentation score values, had higher levels of 25(OH)D (0.6 nmol/l; 95% CI 0.2, 1.0; per unit increase in skin colour score; N = 5649). These children also used more protection against the damaging effects of UVR. Conclusions In this population taking protective measures against sunburn and skin cancer does not seem to remove the positive effect that having a less pigmented skin has on vitamin D production. Our findings require further replication as skin pigmentation showed only a small effect on circulating 25(OH)D. PMID:24924479

  10. Skin pigmentation evaluation in broilers fed natural and synthetic pigments.

    PubMed

    Castañeda, M P; Hirschler, E M; Sams, A R

    2005-01-01

    Broiler carcass skin color is important in the United States and Mexico. This study evaluated the use of natural and synthetic pigments in broiler diets at commercial levels. Birds were fed natural or synthetic pigments at low or high levels, simulating US and Mexican commercial practices. Skin color was measured during live production (3 to 7 wk of age) and after slaughter and chilling. The natural pigments had consistently greater skin b* values (yellowness) than the synthetic pigments. The high levels produced greater skin b* values than the low levels, regardless of source. The synthetic pigments had a slower increase in skin b* but reached the same level as the natural low by 7 wk. There was no difference in skin a* values (redness) due to pigment source or level or the age of the bird. By 7 wk, all pigment sources approached plateau levels in the blood, but the synthetic pigment diet produced higher blood levels of yellow and red pigments than the natural pigment diets. Processing intensified skin yellowness and reduced skin redness. These data suggest that although synthetic pigments might have been absorbed better than natural ones, natural pigments were more efficient at increasing skin yellowness and there were only small differences between high and low levels for each pigment source. This finding may allow reduction in pigment use and feed cost to achieve the same skin acceptance by the consumer. PMID:15685954

  11. Complications of Macular Peeling

    PubMed Central

    Asencio-Duran, Mónica; Manzano-Muñoz, Beatriz; Vallejo-García, José Luis; García-Martínez, Jesús

    2015-01-01

    Macular peeling refers to the surgical technique for the removal of preretinal tissue or the internal limiting membrane (ILM) in the macula for several retinal disorders, ranging from epiretinal membranes (primary or secondary to diabetic retinopathy, retinal detachment…) to full-thickness macular holes, macular edema, foveal retinoschisis, and others. The technique has evolved in the last two decades, and the different instrumentations and adjuncts have progressively advanced turning into a safer, easier, and more useful tool for the vitreoretinal surgeon. Here, we describe the main milestones of macular peeling, drawing attention to its associated complications. PMID:26425351

  12. Macular dystrophy in Heimler syndrome

    PubMed Central

    Lima, Luiz H.; Barbazetto, Irene A.; Chen, Royce; Yannuzzi, Lawrence A.; Tsang, Stephen H.; Spaide, Richard F.

    2011-01-01

    Purpose To describe the retinal imaging findings in the index patient with Heimler syndrome (OMIM #234580). Design Non-interventional case report. Methods A 29-year-old woman with Heimler syndrome developed bilateral vision loss. Fluorescein angiography (FA), fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) were performed to assess the retinal anatomy and function. Results FA showed mottling of the retinal pigment epithelium (RPE) in the posterior pole and periphery of the retina. FAF revealed hyper and hypoautofluorescent dots corresponding to the RPE mottling observed on FA. SD-OCT documented loss of the inner/outer segments boundary, and RPE thinning. ERG testing excluded generalized rod-cone dysfunction. Conclusion We report an adult-onset macular dystrophy in one of the previously reported patients with Heimler syndrome and hypothesize that this syndrome is probably an expression of a ciliopathy. PMID:21366429

  13. The Impact of Fish and Shellfish Consumption on Age-Related Macular Degeneration

    PubMed Central

    Swenor, Bonnielin K.; Bressler, Susan; Caulfield, Laura; West, Sheila K.

    2013-01-01

    Purpose To determine the relationship between fish and shellfish consumption and age-related macular degeneration (AMD) status in the Salisbury Eye Evaluation (SEE) Study participants. Design A cross-sectional study of dietary and ophthalmologic data. Participants A random sample of 2520 Salisbury, Maryland, residents aged 65 to 84 years. Methods A food frequency questionnaire was used to estimate weekly fish/shellfish consumption for each participant. Age-related macular degeneration status was determined from fundus photographs obtained at baseline and graded by 2 masked readers for drusen size, retinal pigment epithelium abnormalities, geographic atrophy (GA), and choroidal neovascularization (CNV). The association between weekly fish/shellfish intake and risk of AMD was investigated using logistic regression while adjusting for risk factors and correlation between eyes. Main Outcome Measures Status of AMD. Results The distribution of weekly fish/shellfish consumption was not different between specific AMD categories compared with controls (P = 0.6, 0.7, and 0.7 for large drusen, pigment abnormalities, and advanced AMD compared with controls, respectively). Those with advanced AMD (CNV or GA) were significantly less likely to consume fish/shellfish high in omega-3 fatty acids (odds ratio 0.4; confidence interval, 0.2– 0.8). There was no relationship of AMD with intake of crab and oysters combined, each of which has high levels of zinc. Conclusions These data support a protective effect of fish/shellfish intake against advanced AMD. PMID:20630597

  14. Genetics Home Reference: vitelliform macular dystrophy

    MedlinePlus

    ... Association for Macular Diseases and The Macula Foundation) Macular Degeneration Foundation National Organization for Rare Disorders (NORD) Retina ... adult vitelliform macular dystrophy but not age-related macular degeneration. Eur J Hum Genet. 2000 Apr;8(4): ...

  15. Vitreoschisis in macular diseases

    PubMed Central

    Gupta, Priya; Yee, Kenneth M P; Garcia, Patricia; Rosen, Richard B; Parikh, Jignesh; Hageman, Gregory S; Sadun, Alfredo A; Sebag, J

    2014-01-01

    Objectives Vitreoschisis is a possible pathogenic mechanism in macular diseases. Thus, the vitreoretinal interface was evaluated in monkey eyes and patients with various macular diseases in search of vitreoschisis. It is hypothesised that vitreoschisis is present in macular holes (MH) and macular pucker (MP), but not in other maculopathies. Methods Histopathology was studied in 14 monkey eyes and a vitrectomy specimen of a patient with macular pucker. Optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) was performed in 239 eyes: 45 MH, 45 MP, 51 dry age-related macular degeneration (AMD), 53 non-proliferative diabetic retinopathy (NPDR) and 45 controls. Results Immunohistochemistry demonstrated lamellae in the posterior vitreous cortex of 12/14 (86%) monkey eyes. With OCT/SLO, vitreoschisis was detected in 24/45 (53%) MH and 19/45 (42%) MP eyes, but in only 7/53 (13%) NPDR, 3/51 (6%) AMD and 3/45 (7%) control eyes (p<0.001 for all comparisons). Rejoining of the inner and outer walls of the split posterior vitreous cortex was visible in 16/45 (36%) MH eyes and 15/45 (33%) MP eyes. Histopathology of the MP specimen confirmed a split with rejoining in the posterior vitreous cortex. Conclusions Vitreoschisis was detected in half of eyes with MH and MP, but much less frequently in controls, AMD and NPDR patients. These findings suggest that anomalous PVD with vitreoschisis may be pathogenic in MH and MP. PMID:20584710

  16. 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

  17. Monitoring VEGF levels with low-volume sampling in major vision-threatening diseases: age-related macular degeneration and diabetic retinopathy.

    PubMed

    Hsu, Min-Yen; Chen, Shih-Jen; Chen, Kuan-Hung; Hung, Yu-Chien; Tsai, Hin-Yeung; Cheng, Chao-Min

    2015-06-01

    The purpose of this article is to demonstrate the capacity of paper-based ELISA (P-ELISA) to monitor VEGF in patients requiring treatment for vision-threatening diseases. The most commonly encountered vision-threatening diseases are age-related macular degeneration (AMD) and diabetic retinopathy (DR), both of which may require short-term or life-long anti-VEGF injection treatment therapy. Accurate measurement of VEGF concentration in aqueous humor can provide significant and timely information to diagnose the disease state. Adequate and precise therapy may consequently be provided. At odds with conventional diagnostic approaches is the fact that a maximum of only 200 microliters of aqueous humor can be safely removed from the eye for testing. Fortunately, new diagnostic platforms, such as P-ELISA, require only minute volumes, i.e., approximately 2 microliters per test "well" and approximately 40 microliters total to quantify VEGF levels, and the testing process takes less than an hour. Thus, point-of-care (POC) diagnostics, such as P-ELISA, should be examined and improved upon as needed in order to develop an efficient tool for outpatient clinics and others to obtain semi-quantitative results that might facilitate accurate dosing of anti-VEGF treatment and delay or prevent the progression of AMD and DR. PMID:25923964

  18. Association of gene polymorphism with serum levels of inflammatory and angiogenic factors in Pakistani patients with age-related macular degeneration

    PubMed Central

    Ambreen, Fareeha; Ismail, Muhammad

    2015-01-01

    Purpose To study the association of serum levels of inflammatory mediators and angiogenic factors with genetic polymorphism in Pakistani age-related macular degeneration (AMD) patients. Methods This was a cross-sectional and case-control study that included 90 AMD patients diagnosed through slit-lamp examination, fundoscopy, and ocular coherence tomography. For reference and comparison purposes, 100 healthy age-matched subjects (controls) were also recruited. IL-6, IL-8, VEGF, and CRP levels were estimated in the serum samples of patients and control subjects. Using restriction fragment length polymorphism, single nucleotide polymorphisms were studied in IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227543), VEGF (rs3025039, rs699947), and CRP genes (rs1205, rs1130864). Since the data were obtained from a sample population, the Box–Cox transformation algorithm was applied to reduce heterogeneity of error. Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD. Genotype and allele frequencies were compared through χ2 tests applying Hardy–Weinberg equilibrium. The serum concentrations of IL-6 and IL-8, VEGF, and CRP between homozygotes and heterozygotes were compared through one-way ANOVA. Significance level was p<0.05. Results Compared to control subjects, serum IL-6 (p<0.0001), IL-8 (p<0.0001), VEGF (p<0.0001), and CRP (p<0.0001) levels were significantly elevated in the AMD patients. For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001). Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002). Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038). However, no significant alteration in serum CRP levels was detected in hetero- or homozygotes for rs1205 and rs1130864 SNPs. Conclusions Serum IL-6, IL-8, and VEGF levels are substantially increased in AMD, and the levels coincide with polymorphism in the respective gene. No such relationship appears to exist with regard to SNPs of CRP. PMID:26330749

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

    ClinicalTrials.gov

    2016-03-22

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

  20. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  1. 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.

  2. Peripheral retinal detachments and retinal pigment epithelial atrophic tracts secondary to central serous pigment epitheliopathy. 1984.

    PubMed

    Yannuzzi, Lawrence A; Shakin, Jeffrey L; Fisher, Yale L; Altomonte, Mary Ann

    2012-02-01

    Twenty-five patients with central serous pigment epitheliopathy (CSP), also known as central serous chorioretinopathy, have been observed to have inferior hemispheric retinal pigment epithelial atrophic tracts, presumptive of antecedent retinal detachments. Five of these patients were noted to have clinically discernible, dependent peripheral retinal detachments. The clinical and fluorescein angiographic features of these patients are reviewed. Alterations in the retina, the retinal pigment epithelium (RPE) and the choroid are also described. They include the commonly associated manifestations of CSP such as RPE leaks and macular detachment as well as some newly recognized disturbances such as retinal capillary dilatation (telangiectasia), retinal capillary leakage, retinal lipid deposition, cystoid macular edema, choriocapillaris atrophy, choroidal neovascularization and disciform scarring. PMID:22451960

  3. 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.

  4. 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

    The role of foliar nitrogen (N) in the seasonal dynamics and vertical canopy distribution of photosynthetic pigments, photosynthetic capacity, and carbon (C) storage was investigated in boreal broadleaved species. The study was conducted at two different aged stands (60 y and 15 y) in 1994 and 1996 in Saskatchewan, Canada as part of the Boreal Ecosystem-Atmosphere Study (BOREAS). Foliage in upper and lower strata was examined for aspen (Populus tremuloides Michx.) and its associated hazelnut shrub (Corylus americana Walt.). We determined that C accumulation, expressed as dry mass per unit leaf area (mg C cm (exp -2)), was linearly dependent on N content (approximately 0.3- 3.5 mg N cm (exp -2))(r (exp 2) = 0.93, n=383, P less than 0.001) when eleven foliage groups were defined according to species, site, and developmental stage. C assembly was greatest in the upper aspen strata of both sites (seasonal average, 40.1 plus or minus 0.6 mg C cm (exp -2)), intermediate in the lower aspen strata (32.7 plus or minus 0.6), and considerably lower, and similar, in the hazelnut shrub layers (23.7 plus or minus 0.6) and in expanding aspen leaves (23.8 plus or minus 0.5); the lowest C assembly per unit N occurred in the two youngest, emerging leaf groups (17.1 plus or minus 0.6). Other relationships among physiological and biochemical variables were typically non-linear and were confounded by inclusion of the three groups of young (i.e., emerging or expanding) leaves, unless these were separately identified. Net C uptake, measured as photosynthetic capacity (A (sub max), micromole CO2 m (exp -2) s (exp -1)), was greater in aspen throughout the season, and optimal in mid-summer at a C:N ratio of approximately 18 (approximately 2.3 %N). When young leaves were excluded and logarithms of both variables were used, A (sub max) was approximately linearly dependent on N (mg N cm (exp-2) (r (exp 2) = 0.85, n= 193, P less than 0.001), attributed to incorporation of N into photosynthetic 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.

  5. [Uveitic macular edema].

    PubMed

    Fardeau, C; Champion, E; Massamba, N; LeHoang, P

    2015-01-01

    Macular edema may complicate anterior, intermediate, and posterior uveitis, which may be due to various infectious, tumoral, or autoimmune etiologies. Breakdown of the internal or external blood-retinal barrier is involved in the pathogenesis of inflammatory macular edema. Optical coherence tomography has become standard in confirming the diagnosis of macular thickening, due to its non-invasive, reproducible and sensitivity characteristics. Fluorescein and indocyanine green angiography allows for, in addition to study of the macula, screening for associated vasculitis, detection of ischemic areas, easy diagnosis of preretinal, prepaillary or choroidal neovascular complications, and it can provide etiological information and may be required to evaluate the therapeutic response. Treatment of inflammatory macular edema requires specific treatment in cases of infectious or tumoral etiologies. If it remains persistent, or occurs in other etiologies, anti-inflammatory treatments are needed. Steroid treatment, available in intravitreal, subconjunctival and sub-Tenon's routes, are widely used. Limitations of local use include induced cataract and glaucoma, and their short-lasting action. Such products may reveal retinal infection. Thus, bilateral chronic sight-threatening posterior uveitis often requires systemic treatment, and steroids represent the classic first-line therapy. In order to reduce the daily steroid dose, immunosuppressant or immunomodulatory drugs may be added. Certain of these compounds are now available intravitreally. PMID:25547721

  6. High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling.

    PubMed

    Qi, Weiwei; Yang, Chuan; Dai, Zhiyu; Che, Di; Feng, Juan; Mao, Yuling; Cheng, Rui; Wang, Zhongxiao; He, Xuemin; Zhou, Ti; Gu, Xiaoqiong; Yan, Li; Yang, Xia; Ma, Jian-Xing; Gao, Guoquan

    2015-04-01

    Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular complication of diabetes. The current study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contribute to skin wound-healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved the functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous microvessels, increased skin thickness, improved numbers and functions of circulating EPCs, and accelerated wound healing compared with wild-type mice. Overexpression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced Wnt signaling activation downstream of the PEDF interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing in the process of angiogenesis and vasculogenesis through the inhibition of Wnt/?-catenin signaling. PMID:25368097

  7. Insulin resistance is associated with elevated serum pigment epithelium-derived factor (PEDF) levels in morbidly obese patients.

    PubMed

    Gattu, Arijeet K; Birkenfeld, Andreas L; Jornayvaz, Francois; Dziura, James; Li, Fangyong; Crawford, Susan E; Chu, Xin; Still, Christopher D; Gerhard, Glenn S; Chung, Chuhan; Samuel, Varman

    2012-12-01

    Obesity is a significant risk factor for developing diabetes. Pigment epithelium-derived factor (PEDF) has been identified by experimental and clinical studies as both a causative and counter-regulatory factor in the metabolic syndrome. We set out to determine whether serum PEDF levels correlated with the degree of insulin resistance in morbidly obese patients. Sera from 53 patients who were evaluated prior to gastric bypass surgery were analyzed for PEDF levels using a commercial ELISA. None of the patients were on diabetes medications prior to enrollment. Baseline data included BMI, serum glucose and insulin, and homeostasis model assessment (HOMA) scores. Patients were stratified based on HOMA score and glucose levels into three groups: insulin sensitive (IS): HOMA <2 and glucose <126; insulin resistant (IR): HOMA >2 and glucose ≤126; and diabetes mellitus (DM): HOMA >2 and glucose >126. Pre- and post-gastric bypass sera from 12 patients were obtained for serial assessment of metabolic parameters and PEDF levels. PEDF secretion was assessed in primary human hepatocytes, HCC cells, and cultured adipocytes in the absence and presence of high glucose media. No significant differences in age, gender, and BMI were found among the three groups. PEDF levels were similar between IR patients and the other groups, but were significantly higher in DM compared to IS patients (p = 0.01). Serum PEDF in individual patients declined significantly after gastric bypass (p = 0.006). High glucose media led to significantly higher PEDF release by human hepatocytes in vitro (p = 0.016). These data demonstrate that serum PEDF concentrations better relate to insulin resistance than to adiposity and suggest that PEDF expression is closely linked to the development of insulin resistance. PMID:22547263

  8. Low-level night-time light therapy for age-related macular degeneration (ALight): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. The only treatments currently available, such as ranibizumab injections, are for neovascular AMD, which accounts for only 10 to 15% of people with the condition. Hypoxia has been implicated as one of the primary causes of AMD, and is most acute at night when the retina is most metabolically active. By increasing light levels at night, the metabolic requirements of the retina and hence the hypoxia will be considerably reduced. This trial seeks to determine whether wearing a light mask that emits a dim, green light during the night can prevent the progression of early AMD. Methods/design ALight is a Phase I/IIa, multicentre, randomized controlled trial. Sixty participants (55 to 88 years old) with early AMD in one eye and neovascular AMD (nAMD) in the fellow eye will be recruited from nAMD clinics. They will be randomized (in the ratio 1:1), either to receive the intervention or to be in the untreated control group, stratified according to risk of disease progression. An additional 40 participants with healthy retinal appearance, or early AMD only, will be recruited for a baseline cross-sectional analysis. The intervention is an eye mask that emits a dim green light to illuminate the retina through closed eyelids at night. This is designed to reduce the metabolic activity of the retina, thereby reducing the potential risk of hypoxia. Participants will wear the mask every night for 12 months. Ophthalmologists carrying out monthly assessments will be masked to the treatment group, but participants will be aware of their treatment group. The primary outcome measure is the proportion of people who show disease progression during the trial period in the eye with early AMD. A co-primary outcome measure is the rate of retinal adaptation. As this is a trial of a CE-marked device for an off-label indication, a further main aim of this trial is to assess safety of the mask in the cohort of participants with AMD. Trial registration International Standard Randomised Controlled Trials Register: ISRCTN82148651 PMID:24965385

  9. INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA

    PubMed Central

    Bailey, Clare; Loewenstein, Anat; Massin, Pascale

    2015-01-01

    Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema. Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials. Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose. Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans. PMID:26352555

  10. Modulation of neutrophil superoxide response and intracellular diacylglyceride levels by the bacterial pigment pyocyanin.

    PubMed Central

    Muller, M; Sorrell, T C

    1997-01-01

    Low concentrations of pyocyanin are reported to enhance superoxide production by human neutrophils exposed to various stimuli, yet the mechanism remains unknown. Using lucigenin-enhanced chemiluminescence, we examined the kinetics of the neutrophil superoxide response in the presence of pyocyanin. At all concentrations (12.5 to 200 microM), pyocyanin decreased the peak superoxide response while prolonging the duration of the response. The prolonged response may be associated with an observed increase in intracellular diacylglyceride levels due to pyocyanin exposure. PMID:9169797

  11. 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

  12. 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

  13. 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. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26564985

  14. 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. PMID:23933169

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

    PubMed

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

    2014-01-01

    Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids ( ω -3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω -3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of ω -3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω -3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD. PMID:24672708

  16. 'Toy' laser macular burns in children: 12-month update.

    PubMed

    Raoof, N; O'Hagan, J; Pawlowska, N; Quhill, F

    2016-03-01

    PurposeThere is increasing evidence that high-powered hand-held laser devices cause retinal injury. We present 12-month follow-up data for three patients that we previously reported with such retinal injuries.MethodsA retrospective case series of three children with maculopathy secondary to exposure to high-power hand-held laser devices. All children underwent clinical examination and spectral domain optical coherence tomography (SD-OCT) at presentation and follow-up. Fundus-controlled microperimetry was also undertaken 12-19 months after exposure.ResultsThree children sustained macular injury after exposure to a high-powered hand-held laser. Acutely, they presented with a 'vitelliform-like' maculopathy with reduced vision. Over the course of follow-up, the best corrected Snellen acuity in all three patients improved to 'normal' levels (range 6/6-6/9). Long-term deficits in foveal retinal sensitivity were identified in two patients using fundus-controlled microperimetry. SD-OCT imaging showed persistent disruption of the foveal outer photoreceptor layers in all three children.ConclusionAlthough visual acuity improved over time, deficits in microperimetry and SD-OCT persisted. All three children had retinal pigment epithelium changes, requiring follow-up for longer-term sequelae of laser injuries such as expansion of retinal atrophy and development of choroidal neovascular membranes. PMID:26611842

  17. Evaluation of an oral telomerase activator for early age-related macular degeneration - a pilot study

    PubMed Central

    Dow, Coad Thomas; Harley, Calvin B

    2016-01-01

    Purpose Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA)-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease. Method Thirty-eight (38) patients were randomly assigned to a 1-year, double-blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes. Results The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation]) improved 0.97 dB compared to placebo (P-value 0.02) and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04). Conclusion The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement. PMID:26869760

  18. Photosynthetic Pigments in Diatoms.

    PubMed

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

    2015-09-01

    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

  19. 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

  20. Documentation of Spontaneous Macular Hole Closure in Macular Telangiectasia Type 2 Using Multimodal Imaging.

    PubMed

    Balaratnasingam, Chandrakumar; Dansingani, Kunal; Dhrami-Gavazi, Elona; Yu, Suqin; Freund, K Bailey; Yannuzzi, Lawrence A

    2015-09-01

    Macular holes in the setting of macular telangiectasia type 2 can be difficult to manage. The rates of anatomical closure after macular hole surgery are less favorable in patients with macular telangiectasia than in those with idiopathic macular holes. These differences may be due to the influence of unique pathogenic mechanisms that modulate macular hole dynamics in patients with macular telangiectasia. In this report, the authors document the multimodal imaging findings of a patient with macular telangiectasia demonstrating spontaneous macular hole closure. These findings may improve the understanding of the natural course of this entity and may have relevance for clinical management. PMID:26431306

  1. 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

  2. Diabetic Macular Edema

    PubMed Central

    Gundogan, Fatih C.; Yolcu, Umit; Akay, Fahrettin; Ilhan, Abdullah; Ozge, Gokhan; Uzun, Salih

    2016-01-01

    Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. Sources of data selection: The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article.

  3. Birthmarks - pigmented

    MedlinePlus

    ... its own appearance: Cafe-au-lait spots are light tan, the color of coffee with milk. Moles are small clusters of colored skin cells. Mongolian spots (also called Mongolian blue ... dark or light skin Growth of hair from pigmented skin Skin ...

  4. 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

  5. Effect of fluazifop-p-butyl treatment on pigments and polyamines level within tissues of non-target maize plants.

    PubMed

    Horbowicz, Marcin; Sempruch, Cezary; Kosson, Ryszard; Koczkodaj, Danuta; Walas, Dajana

    2013-09-01

    Fluazifop-p-butyl (FL) is one of the most popular graminicides from arylophenoxypropionate group. These herbicides act as inhibitors of acetyl-CoA carboxylase (ACCase) that catalyzes the formation of malonyl-CoA during metabolism of lipids and/or of some secondary compounds. On the other hand arylopropionates and cyclohexanediones cause phytotoxic effects by stimulating free-radicals generation and causing oxidative stress in susceptible plants. However, the importance of disturbances in plant pigments and polyamines accumulation for this effect is not clear. The aim of this work is to quantify the phytotoxicity of FL to non target maize plant and to explain how photosynthetic pigments, anthocyanins (ANC) and polyamines participate in this interaction. Obtained results showed reduction of chlorophyll a and b, but only in case of the highest herbicide dose. Lower FL concentrations caused increase of the photosynthetic pigments, or were not effective. A similar effect was stated for putrescine, while spermidine was reduced within epicotyl of leaf tissues. In case of 2-phenylethylamine (PEA), there was observed a lack of significant changes within leaves and an increase in epicotyl under the middle and the highest dose of the herbicide. Moreover, FL induced ANC accumulation in epicotyls of maize seedlings. The activity of such key enzymes of polyamine biosynthesis as: ornithine decarboxylase (ODC) and lysine decarboxylase (LDC), increased in leaves treated with herbicide at the lowest concentration and decreased under the highest. However, in case of epicotyls the decreasing tendency was observed with the exception of ODC under the highest FL dose. The activity of tyrosine decarboxylase (TyDC) was importantly elevated only within epicotyls under the lower FL concentrations. It was concluded that FL inhibits maize growth, and the intensity of the effect is positively correlated with the herbicide concentration. The phenomenon was related to changes in content of pigments, polyamines and activity of studied enzymes. PMID:25149239

  6. 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. PMID:26909639

  7. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration.

    PubMed

    Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

    2014-07-01

    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

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

    PubMed

    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

    2016-02-01

    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 CTNNA1 gene (encoding α-catenin 1) 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 demonstrated increased cell shedding and the presence of large multinucleated RPE cells, suggesting defects in intercellular adhesion and cytokinesis. This study identifies CTNNA1 gene variants as a cause of macular dystrophy, indicates 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

  9. 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 regional phenotypes. PMID:25446321

  10. Sunlight Exposure, Pigmentation, and Incident Age-Related Macular Degeneration

    PubMed Central

    Klein, Barbara E. K.; Howard, Kerri P.; Iyengar, Sudha K.; Sivakumaran, Theru A.; Meyers, Kristin J.; Cruickshanks, Karen J.; Klein, Ronald

    2014-01-01

    Purpose. Examine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD. Methods. Subjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color. Results. Incidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD. Conclusions. Modest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype. PMID:25125603

  11. Pleiotropy in the melanocortin system: expression levels of this system are associated with melanogenesis and pigmentation in the tawny owl (Strix aluco).

    PubMed

    Emaresi, Guillaume; Ducrest, Anne-Lyse; Bize, Pierre; Richter, Hannes; Simon, Celine; Roulin, Alexandre

    2013-10-01

    The adaptive function of melanin-based coloration is a long-standing debate. A recent genetic model suggested that pleiotropy could account for covariations between pigmentation, behaviour, morphology, physiology and life history traits. We explored whether the expression levels of genes belonging to the melanocortin system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many pleiotropic effects, are associated with melanogenesis (through variation in the expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin-based coloration. We considered the tawny owl (Strix aluco) because individuals vary continuously from light to dark reddish, and thus, colour variation is likely to stem from differences in the levels of gene expression. We measured gene expression in feather bases collected in nestlings at the time of melanin production. As expected, the melanocortin system was associated with the expression of melanogenic genes and pigmentation. Offspring of darker reddish fathers expressed PC1/3 to lower levels but tended to express PC2 to higher levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH, while the convertase enzyme PC2 cleaves ACTH to produce α-melanin-stimulating hormone (α-MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while α-MSH induces eumelanogenesis. We therefore conclude that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may account for part of the interindividual variation in melanin-based coloration in nestling tawny owls. Pleiotropy may thus account for the covariation between phenotypic traits involved in social interactions (here pigmentation) and life history, morphology, behaviour and physiology. PMID:24033481

  12. 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. PMID:26292978

  13. Mechanism of inflammation in age-related macular degeneration: an up-to-date on genetic landmarks.

    PubMed

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

    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

  14. 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

  15. Macular Degeneration - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Macular Degeneration URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Macular Degeneration - Multiple Languages To use the sharing features on ...

  16. Inflammation and its role in age-related macular degeneration.

    PubMed

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms. PMID:26852158

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

    PubMed

    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

  18. 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

  19. Skin Pigmentation Disorders

    MedlinePlus

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  20. Multimodality imaging in macular telangiectasia 2: A clue to its pathogenesis

    PubMed Central

    Wu, Lihteh

    2015-01-01

    Macular telangiectasia type 2 also known as idiopathic perifoveal telangiectasia and juxtafoveolar retinal telangiectasis type 2A is an acquired bilateral neurodegenerative macular disease that manifests itself during the fifth or sixth decades of life. It is characterized by minimal dilatation of the parafoveal capillaries with graying of the retinal area involved, a lack of lipid exudation, right-angled retinal venules, refractile deposits in the superficial retina, hyperplasia of the retinal pigment epithelium, foveal atrophy, and subretinal neovascularization (SRNV). Our understanding of the disease has paralleled advances in multimodality imaging of the fundus. Optical coherence tomography (OCT) images typically demonstrate the presence of intraretinal hyporeflective spaces that are usually not related to retinal thickening or fluorescein leakage. The typical fluorescein angiographic (FA) finding is a deep intraretinal hyperfluorescent staining in the temporal parafoveal area. With time, the staining may involve the whole parafoveal area but does not extend to the center of the fovea. Long-term prognosis for central vision is poor, because of the development of SRNV or macular atrophy. Its pathogenesis remains unclear but multimodality imaging with FA, spectral domain OCT, adaptive optics, confocal blue reflectance and short wave fundus autofluorescence implicate Müller cells and macular pigment. Currently, there is no known treatment for this condition. PMID:26139799

  1. Monascus pigments.

    PubMed

    Feng, Yanli; Shao, Yanchun; Chen, Fusheng

    2012-12-01

    Monascus pigments (MPs) as natural food colorants have been widely utilized in food industries in the world, especially in China and Japan. Moreover, MPs possess a range of biological activities, such as anti-mutagenic and anticancer properties, antimicrobial activities, potential anti-obesity activities, and so on. So, in the past two decades, more and more attention has been paid to MPs. Up to now, more than 50 MPs have been identified and studied. However, there have been some reviews about red fermented rice and the secondary metabolites produced by Monascus, but no monograph or review of MPs has been published. This review covers the categories and structures, biosynthetic pathway, production, properties, detection methods, functions, and molecular biology of MPs. PMID:23104643

  2. 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.

  3. 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].

  4. 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…

  5. 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.

  6. Effect of Storage Temperature on Key Functions of Cultured Retinal Pigment Epithelial Cells

    PubMed Central

    Pasovic, Lara; Eidet, Jon Roger; Brusletto, Berit S.; Lyberg, Torstein; Utheim, Tor P.

    2015-01-01

    Purpose. Replacement of the diseased retinal pigment epithelium (RPE) with cells capable of performing the specialized functions of the RPE is the aim of cell replacement therapy for treatment of macular degenerative diseases. A storage method for RPE is likely to become a prerequisite for the establishment of such treatment. Herein, we analyze the effect of storage temperature on key functions of cultured RPE cells. Methods. Cultured ARPE-19 cells were stored in Minimum Essential Medium at 4°C, 16°C, and 37°C for seven days. Total RNA was isolated and the gene expression profile was determined using DNA microarrays. Comparison of the microarray expression values with qRT-PCR analysis of selected genes validated the results. Results. Expression levels of several key genes involved in phagocytosis, pigment synthesis, the visual cycle, adherens, and tight junctions, and glucose and ion transport were maintained close to control levels in cultures stored at 4°C and 16°C. Cultures stored at 37°C displayed regulational changes in a larger subset of genes related to phagocytosis, adherens, and tight junctions. Conclusion. RPE cultures stored at 4°C and 16°C for one week are capable of maintaining the expression levels of genes important for key RPE functions close to control levels. PMID:26448872

  7. 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

  8. 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

  9. VEGF-A and the NLRP3 Inflammasome in Age-Related Macular Degeneration.

    PubMed

    Marneros, Alexander G

    2016-01-01

    The pathomechanisms that lead to age-related macular degeneration (AMD) are only partially understood. The NLRP3 inflammasome has been shown to be activated in the retinal pigment epithelium (RPE) in eyes with AMD. However, it is not known whether inflammasome activation is a cause or consequence of pathologic changes in AMD. A roadblock to defining the role of inflammasome activation and pathways that regulate it for AMD has been the lack of a mouse model that forms AMD-like pathologies in an age-dependent manner in which the role of the inflammasome can be investigated using genetic studies. We have recently identified such a mouse model, in which increased VEGF-A levels result in early degenerative changes of the RPE, followed by cardinal features of both nonexudative and neovascular AMD. Importantly, higher VEGF-A levels lead to increased oxidative damage and a sub-retinal inflammatory infiltrate that are associated with NLRP3 inflammasome activation in the RPE. Targeting the NLRP3 inflammasome inhibited AMD-like pathologies in these mice. These findings suggest that inhibiting the NLRP3 inflammasome or pathways that regulate it may provide novel therapeutic approaches for the treatment of both forms of AMD. PMID:26427397

  10. VITAMIN D DEFICIENCY IN NEOVASCULAR VERSUS NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION

    PubMed Central

    Itty, Sujit; Day, Shelley; Lyles, Kenneth W.; Stinnett, Sandra S.; Vajzovic, Lejla M.; Mruthyunjaya, Prithvi

    2014-01-01

    Purpose To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. Methods Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. Results Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non–age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18– 0.68) odds ratio for NVAMD. Conclusion This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD. PMID:24946100

  11. 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

  12. Macular thickness and macular volume measurements using spectral domain optical coherence tomography in normal Nepalese eyes

    PubMed Central

    Pokharel, Amrit; Shrestha, Gauri Shankar; Shrestha, Jyoti Baba

    2016-01-01

    Purpose To record the normative values for macular thickness and macular volume in normal Nepalese eyes. Methods In all, 126 eyes of 63 emmetropic subjects (mean age: 21.17±6.76 years; range: 10–37 years) were assessed for macular thickness and macular volume, using spectral domain-optical coherence tomography over 6×6 mm2 in the posterior pole. A fast macular thickness protocol was employed. Statistics such as the mean, median, standard deviation, percentiles, and range were used, while a P-value was set at 0.05 to test significance. Results Average macular thickness and total macular volume were larger in males compared to females. With each year of increasing age, these variables decreased by 0.556 μm and 0.0156 mm3 for average macular thickness and total macular volume, respectively. The macular thickness was greatest in the inner superior section and lowest at the center of the fovea. The volume was greatest in the outer nasal section and thinnest in the fovea. The central subfield thickness (r=−0.243, P=0.055) and foveal volume (r=0.216, P=0.09) did not correlate with age. Conclusion Males and females differ significantly with regard to macular thickness and macular volume measurements. Reports by other studies that the increase in axial length reduced thickness and volume, were negated by this study which found a positive correlation among axial length, thickness, and volume. PMID:27041990

  13. Laser therapy and macular degeneration

    NASA Astrophysics Data System (ADS)

    Menchini, Ugo; Virgili, Gianni; Giansanti, Fabrizio; Giacomelli, Giovanni; Cappelli, Stefania

    2001-10-01

    Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the possibility of reducing visual loss in patients affected by CNV. With PDT, a photosensitizer (verteporfin, VisudyneTM) is injected intravenously, and it selectively binds to new vessels; low-power laser light exposure then activates the drug, leading to oxidative damage of the endothelium and new vessels thrombosis. Yet, other therapies, such as transpupillary termotherapy, or the use of photocoagulation to cause feeder-vessel occlusion, could proof effective, but they need further investigation.

  14. Iron upregulates melanogenesis in cultured retinal pigment epithelial cells

    PubMed Central

    Wolkow, Natalie; Li, Yafeng; Maminishkis, Arvydas; Song, Ying; Alekseev, Oleg; Iacovelli, Jared; Song, Delu; Lee, Jennifer C.; Dunaief, Joshua L.

    2014-01-01

    The purpose of our studies was to examine the relationship between iron and melanogenesis in retinal pigment epithelial cells, as prior observations had suggested that iron may promote melanogenesis. This relationship has potential clinical importance, as both iron overload and hyperpigmentation are associated with age-related macular degeneration (AMD). Human fetal retinal pigment epithelial cells and ARPE-19 cells were treated with iron in the form of ferric ammonium citrate, after which quantitative RT-PCR and electron microscopy were performed. Melanogenesis genes tyrosinase, tyrosinase-related protein 1, Hermansky-Pudlak Syndrome 3, premelanosome protein and dopachrome tautomerase were upregulated, as was the melanogenesis-controlling transcription factor, microphthalmia-associated transcription factor (MITF). Iron-treated cells had increased pigmentation and melanosome number. Multiple transcription factors upstream of MITF were upregulated by iron. PMID:25277027

  15. ‘Toy' laser macular burns in children

    PubMed Central

    Raoof, N; Chan, T K J; Rogers, N K; Abdullah, W; Haq, I; Kelly, S P; Quhill, F M

    2014-01-01

    Purpose Laser ‘toys' can be purchased online and imported with relative ease; the variety of such devices is a potential public safety concern. We describe five children with maculopathy following exposure to laser ‘toys'. Methods Case series of maculopathy following exposure to laser ‘toys'. Results Five children were seen in our Ophthalmic Unit with macular injuries following exposure to laser ‘toys'. Clinically, three children had an acute vitelliform-like maculopathy which resolved to leave sub-foveal retinal pigment epithelium changes with reduced vision. One case was complicated by a choroidal neovascular membrane. Conclusion Laser ‘toys', which resemble laser pointers, are increasingly available over the internet. Such ‘toys' may not meet safety standards. Retinal injury in childhood following exposure to laser ‘toys' is a public safety concern. PMID:24434663

  16. Bilateral Cystoid Macular Edema Secondary to Paclitaxel Treatment.

    PubMed

    Tezcan, Yilmaz; Surmeli, Mustafa; Tastekin, Didem; Koc, Mehmet

    2015-09-01

     Cystoid macular edema is rarely observed secondary to paclitaxel treatment. A 55-year-old female patient was applied five cures of paclitaxel and carboplatin chemotherapy after being diagnosed with metastatic ovarian cancer. The patient had a normal bilateral vision prior to the chemotherapy treatments. After the fifth cure, the patient complained of bilateral vision loss, which was more severe in the left eye. Ophthalmologic examination revealed that right eye vision was 4/10 blurred without glasses and 7/10 blurred with glasses, left eye vision was 1/10 blurred without glasses and 4/10 blurred with glasses. Pathology was not detected during the biomicroscopic examination. Fundus examination of the patient revealed pigment epithelium irregularity, which was found to be less in the right eye, and it was found a decrease in foveal cavity. For fundus examination, the patient underwent fundus fluorescein angiography (FFA) and optical coherence tomography (OCT). FFA revealed fluorescein leakage and cystoid appearance particularly more apparent in the left eye. Thickening in the macula and cystoid space was observed particularly more in the left eye in the OCT measurement. In conclusion, we presented our case as a rarely observed cystoid macular edema secondary to paclitaxel treatment. PMID:26317603

  17. 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

  18. Pulsed dye laser for the treatment of macular amyloidosis: a case report.

    PubMed

    Barsky, Maya; Buka, Robert L

    2014-04-01

    Macular amyloidosis causes an eruption of brown pigment in the skin when keratin is altered. The resulting hyperpigmentation, which often leads to patient distress, generally has unsatisfactory treatment options. Among the treatment modalities that have been used for amyloidosis, the pulsed dye laser (PDL) has shown success in the treatment of nodular amyloidosis, and the Q-switched Nd:YAG laser has reduced the appearance of amyloid plaques in macular amyloidosis. We investigated the effects of repeated PDL treatments in a 57-year-old man with recalcitrant macular amyloidosis. The patient was treated with 3 treatment sessions of PDL at 2-week intervals. Based on patient self-assessment and our own photographic analysis, improvement of the lesions was noted with each treatment. Macular amyloidosis can be successfully treated using the PDL, which decreases amyloid aggregation and skin hyperpigmentation. This effect from a decrease in collagen and dermatan sulfate synthesis is similar to the mechanism behind the reduction of size of hypertrophic scars using PDL. PMID:24818178

  19. 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...

  20. 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. PMID:26839315

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

    PubMed Central

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

    2016-01-01

    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 that Angptl2 KO 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 the Angptl2 KO 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 from Angptl2 KO 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. PMID:26839315

  2. Combined hamartoma of the retina and retinal pigment epithelium in branchio-otic syndrome.

    PubMed

    Kadaba, Priyanka; Arepalli, Sruthi; Shields, Jerry A; Shields, Carol L

    2014-04-01

    A 15-month-old boy with established branchio-otic syndrome was evaluated for decreased red reflex in the left eye. Fundus examination of left eye revealed a gray epiretinal membrane with retinal traction and ill-defined macular thickening, found on ultrasonography as a dense flat region 1.7 mm in thickness. Enhanced depth imaging optical coherence tomography revealed an epiretinal membrane with macular thickening, retinal folding, and full-thickness retinal disorganization, consistent with combined hamartoma of the retina and retinal pigment epithelium. Over 5 years of follow-up, the branchio-otic syndrome was unchanged and the combined hamartoma remained stable. PMID:24698626

  3. The etiology and molecular genetics of human pigmentation disorders

    PubMed Central

    Baxter, Laura L.; Pavan, William J.

    2012-01-01

    Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically normal human pigmentation encompasses a variety of skin and hair color as well as with punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while clinically abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions, often in different cell types. Thus unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, revealing a common cellular origin and/or common genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities is instructive for understanding normal pathways governing development and function of melanocytes. PMID:23799582

  4. 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

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

    PubMed Central

    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. PMID:26770854

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

    PubMed Central

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

    2016-01-01

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

  7. Genetics and molecular pathology of Stargardt-like macular degeneration.

    PubMed

    Vasireddy, Vidyullatha; Wong, Paul; Ayyagari, Radha

    2010-05-01

    Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third decade of life (i.e., starting in the teenage years). The clinical profile at any given age among STGD3 patients can be variable suggesting that, although STGD3 is a single gene defect, other genetic or environmental factors may play a role in moderating the final disease phenotype. Genetic studies localized the STGD3 disease locus to a small region on the short arm of human chromosome 6, and application of a positional candidate gene approach identified protein truncating mutations in the elongation of very long chain fatty acids-4 gene (ELOVL4) in patients with this disease. The ELOVL4 gene encodes a protein homologous to the ELO group of proteins that participate in fatty acid elongation in yeast. Pathogenic mutations found in the ELOVL4 gene result in altered trafficking of the protein and behave with a dominant negative effect. Mice carrying an Elovl4 mutation developed photoreceptor degeneration and depletion of very long chain fatty acids (VLCFA). ELOVL4 protein participates in the synthesis of fatty acids with chain length longer than 26 carbons. Studies on ELOVL4 indicate that VLCFA may be necessary for normal function of the retina, and the defective protein trafficking and/or altered VLCFA elongation underlies the pathology associated with STGD3. Determining the role of VLCFA in the retina and discerning the implications of abnormal trafficking of mutant ELOVL4 and depleted VLCFA content in the pathology of STGD3 will provide valuable insight in understanding the retinal structure, function, and pathology underlying STGD3 and may lead to a better understanding of the process of macular disease in general. PMID:20096366

  8. Genetics and molecular pathology of Stargardt-like macular degeneration

    PubMed Central

    Vasireddy, Vidyullatha; Wong, Paul; Ayyagaria, Radha

    2010-01-01

    Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third decade of life (i.e., starting in the teenage years). The clinical profile at any given age among STGD3 patients can be variable suggesting that, although STGD3 is a single gene defect, other genetic or environmental factors may play a role in moderating the final disease phenotype. Genetic studies localized the STGD3 disease locus to a small region on the short arm of human chromosome 6, and application of a positional candidate gene approach identified protein truncating mutations in the elongation of very long chain fatty acids-4 gene (ELOVL4) in patients with this disease. The ELOVL4 gene encodes a protein homologous to the ELO group of proteins that participate in fatty acid elongation in yeast. Pathogenic mutations found in the ELOVL4 gene result in altered trafficking of the protein and behave with a dominant negative effect. Mice carrying an Elovl4 mutation developed photoreceptor degeneration and depletion of very long chain fatty acids (VLCFA). ELOVL4 protein participates in the synthesis of fatty acids with chain length longer than 26 carbons. Studies on ELOVL4 indicate that VLCFA may be necessary for normal function of the retina, and the defective protein trafficking and/or altered VLCFA elongation underlies the pathology associated with STGD3. Determining the role of VLCFA in the retina and discerning the implications of abnormal trafficking of mutant ELOVL4 and depleted VLCFA content in the pathology of STGD3 will provide valuable insight in understanding the retinal structure, function, and pathology underlying STGD3 and may lead to a better understanding of the process of macular disease in general. PMID:20096366

  9. Chronic delivery of low-level exogenous current preserves retinal function in pigmented P23H rat.

    PubMed

    Rahmani, Safa; Bogdanowicz, Les; Thomas, Joel; Hetling, John R

    2013-01-14

    Diffuse electrical currents delivered to the eye were investigated in a rat model of retinitis pigmentosa for potentially therapeutic effects. Low-level currents were passed between electrodes placed on the cornea and in the mouth during 30-min sessions two times per week from 4 to 16 weeks of age. Single-flash electroretinograms (ERG) were recorded and analyzed for amplitude and measures of sensitivity, and basic histology was performed. ERG a-wave amplitudes were slightly greater in treated vs. age-matched controls at 16 weeks of age, but the combined thicknesses of the outer nuclear layer and outer segment layer were similar at this age. Treated animals exhibited a significant preservation of b-wave amplitudes, and a striking preservation of rod sensitivity, measured as the stimulus strength required to reach half-saturation of the a-wave. Analysis of the leading edge of the a-wave using a delayed Gaussian function revealed a decrease in the parameter reflecting gain of the phototransduction cascade over the 12-week course of treatment, and no significant change in control animals over the same period. These results suggest that while the exogenous currents failed to preserve the number or gross structure of rods, the responsivity of individual photoreceptors was relatively preserved, perhaps via an increase in efficiency of photon capture (R/photon). This preserved functionality may delay the retraction of bipolar cell dendrites from degenerating photoreceptors. PMID:23147691

  10. A Risk Score for the Prediction of Advanced Age-related Macular Degeneration: Development and Validation in Two Prospective Cohorts

    PubMed Central

    Chiu, Chung-Jung; Mitchell, Paul; Klein, Ronald; Klein, Barbara E.; Chang, Min-Lee; Gensler, Gary; Taylor, Allen

    2014-01-01

    Purpose To develop a clinical eye-specific prediction model for advanced age-related macular degeneration (AMD). Design The Age-Related Eye Disease Study (AREDS) cohort followed for 8 years served as the training dataset and the Blue Mountains Eye Study (BMES) cohort followed for 10 years served as the validation dataset. Participants 4,507 AREDS participants (contributing 1,185 affected vs. 6,992 unaffected eyes) and 2,169 BMES participants (69 affected vs. 3,694 unaffected eyes). Methods Employing Bayes' theorem in a logistic model, we used 8 baseline predictors: age, sex, education level, race, smoking status, and presence of pigment abnormality, soft drusen, and maximum drusen size, to devise and validate a macular risk scoring system (MRSS). We assessed the performance of the MRSS by calculating sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (i.e. c-index). Main Outcome Measures Advanced AMD. Results The internally validated c-indexAREDS (0.88, 95% confidence interval (CI): 0.87 to 0.89) and the externally validated c-indexBMES (0.91, 95% CI: 0.88 to 0.95) suggested an excellent performance of the MRSS. The sensitivity and specificity at the optimal MR score cutoff point “0” were 87.6% and 73.6%, respectively. An application software (App) for iPhone/iPad was also developed as a practical tool for the MRSS. Conclusion The MRSS was developed and validated to provide satisfactory accuracy and generalizability. It may be used to screen patients at risk of developing advanced AMD. PMID:24650555

  11. 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.

  12. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT)

    PubMed Central

    Jaffe, Glenn J.; Martin, Daniel F.; Toth, Cynthia A; Daniel, Ebenezer; Maguire, Maureen G.; Ying, Gui-Shuang; Grunwald, Juan E.; Huang, Jiayan

    2013-01-01

    Objective To describe effects of treatment for one year with ranibizumab or bevacizumab on macular morphology and the association of macular morphology with visual acuity in eyes with neovascular age related macular degeneration (AMD). Design Prospective cohort study within a randomized clinical trial. Participants Participants in the Comparison of Age-related Macular Degeneration Treatments Trials. Methods Participants were assigned randomly to treatment with ranibizumab or bevacizumab on a monthly or as needed schedule. Optical coherence tomography (OCT), fluorescein angiography (FA), color fundus photography (FP), and visual acuity (VA) testing were performed periodically through 52 weeks. Masked readers graded images. General linear models were applied to evaluate effects of time and treatment on outcomes. Main Outcome Measures Fluid type and location, and thickness by OCT, size and lesion composition on FP and FA, and VA. Results Intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium fluid, and retinal, subretinal and subretinal tissue complex thickness decreased in all treatment groups. A higher proportion of eyes treated monthly with ranibizumab had fluid resolution at 4 weeks and the difference persisted through 52 weeks. At 52 weeks, there was little association between the presence of fluid of any type (without regard to fluid location) and the mean VA. However, at all time points, eyes with residual IRF, especially foveal IRF, had worse mean VA (9 letters) than those without IRF. Eyes with abnormally thin (<120 u) or thick (>212u) retinas had worse VA than those with normal thickness (120–212 u). At week 52, eyes with larger neovascular lesions or with foveal scar had worse VA than eyes without these features. Conclusions Anti-vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, with residual large lesions, and with scar also had worse VA. Monthly ranibizumab dosing yielded more eyes with no fluid and an abnormally thin retina, although the long-term significance is unknown. These results have important treatment implications in eyes undergoing anti-VEGF therapy for neovascular AMD. PMID:23642377

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

    PubMed Central

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

    2009-01-01

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

  14. Advances in the management of macular degeneration.

    PubMed

    Singer, Michael

    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

  15. Clinical characteristics and current treatment of age-related macular degeneration.

    PubMed

    Yonekawa, Yoshihiro; Kim, Ivana K

    2015-01-01

    Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

  16. Friction melanosis, friction amyloidosis, macular amyloidosis, towel melanosis: many names for the same clinical entity.

    PubMed

    Siragusa, M; Ferri, R; Cavallari, V; Schepis, C

    2001-01-01

    Macular or friction amyloidosis is a cutaneous entity characterized by a brownish pigmentation distributed on the skin over bony regions of the trunk and limbs after the use, for many years, of a nylon towel or scrub brush to clean the skin. Electron microscopy is necessary for the diagnosis of this dermatosis and reveals deposits of amyloid in the papillary dermis. This condition is relatively unknown in Western countries. In this report, we describe 24 Italian patients affected by friction amyloidosis which was caused by the use of cotton towels, horse-hair gloves or artificial and rough sponges to clean their skin. PMID:11701405

  17. Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration

    PubMed Central

    Jones, B.W.; Watt, C.B.; Vazquez-Chona, F.; Vaughan, D.K.; Organisciak, D.T.

    2008-01-01

    Purpose Our objective was to comprehensively assess the nature and chronology of neural remodeling in retinal degenerations triggered by light-induced retinal damage (LIRD) in adult albino rodents. Our primary hypothesis is that all complete photoreceptor degenerations devolve to extensive remodeling. An hypothesis emergent from data analysis is that the LIRD model closely mimics late-stage atrophic age relared macular degeneration (AMD). Methods Sprague-Dawley (SD) rats received intense light exposures of varied durations and survival times ranging from 0 to 240 days. Remodeling was visualized by computational molecular phenotyping (CMP) of a small molecule library: 4-aminobutyrate (γ), arginine (R), aspartate (D), glutamate (E), glutamine (Q), glutathione (J), glycine (G), and taurine (τ). This library was augmented by probes for key proteins such as rod opsin, cone opsin and cellular retinal binding protein (CRALBP). Quantitative CMP was used to profile 160 eyes from 86 animals in over 6,000 sections. Results The onset of remodeling in LIRD retinas is rapid, with immediate signs of metabolic stress in photoreceptors, the retinal pigmented epithelium (RPE), the choriocapillaris, and Müller cells. In particular, anomalous elevated aspartate levels appear to be an early stress marker in photoreceptors. After the stress phase, LIRD progresses to focal photoreceptor degeneration within 14 days and extensive remodeling by 60 days. RPE and choriocapillaris losses parallel Müller cell distal seal formation, with progressive neuronal migration, microneuroma evolution, fluid channel formation, and slow neuronal death. The remaining retina in advanced light damage can be classified as survivor, light damage (LD), or decimated zones where massive Müller cell and neuronal emigration into the choroid leaves a retina depleted of neurons and Müller cells. These zones and their transitions closely resemble human geographic atrophy. Across these zones, Müller cells manifest extreme changes in the definitive Müller cell τQE signature, as well as CRALBP and arginine signals. Conclusions LIRD retinas manifest remodeling patterns of genetic retinal degeneration models, but involve no developmental complexities, and are ultimately more aggressive, devastating the remaining neural retina. The decimation of the neural retina via cell emigration through the perforated retina-choroid interface is a serious denouement. If focal remodeling in LIRD accurately profiles late stage atrophic age-related macular degenerations, it augurs poorly for simple molecular interventions. Indeed, the LIRD profile in the SD rat manifests more similarities to advanced human atrophic AMD than most genetically or immunologically induced murine models of AMD. PMID:18483561

  18. Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability

    PubMed Central

    Cachafeiro, M; Bemelmans, A-P; Samardzija, M; Afanasieva, T; Pournaras, J-A; Grimm, C; Kostic, C; Philippe, S; Wenzel, A; Arsenijevic, Y

    2013-01-01

    Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure to the visible light, and although cellular processes within photoreceptors have been characterized extensively, the role of the retinal pigment epithelium (RPE) in this model is less well understood. We demonstrate that exposition to intense light causes the immediate breakdown of the outer blood–retinal barrier (BRB). In a molecular level, we observed the slackening of adherens junctions tying up the RPE and massive leakage of albumin into the neural retina. Retinal pigment epithelial cells normally secrete vascular endothelial growth factor (VEGF) at their basolateral side; light damage in contrast leads to VEGF increase on the apical side – that is, in the neuroretina. Blocking VEGF, by means of lentiviral gene transfer to express an anti-VEGF antibody in RPE cells, inhibits outer BRB breakdown and retinal degeneration, as illustrated by functional, behavioral and morphometric analysis. Our data show that exposure to high levels of visible light induces hyperpermeability of the RPE, likely involving VEGF signaling. The resulting retinal edema contributes to irreversible damage to photoreceptors. These data suggest that anti-VEGF compounds are of therapeutic interest when the outer BRB is altered by retinal stresses. PMID:23990021

  19. Aryl hydrocarbon receptor deficiency causes dysregulated cellular matrix metabolism and age-related macular degeneration-like pathology

    PubMed Central

    Hu, Peng; Herrmann, Rolf; Bednar, Amanda; Saloupis, Peter; Dwyer, Mary A.; Yang, Ping; Qi, Xiaoping; Thomas, Russell S.; Jaffe, Glenn J.; Boulton, Michael E.; McDonnell, Donald P.; Malek, Goldis

    2013-01-01

    The aryl hydrocarbon receptor (AhR) is a nuclear receptor that regulates xenobiotic metabolism and detoxification. Herein, we report a previously undescribed role for the AhR signaling pathway as an essential defense mechanism in the pathogenesis of early dry age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that AhR activity and protein levels in human retinal pigment epithelial (RPE) cells, cells vulnerable in AMD, decrease with age. This finding is significant given that age is the most established risk factor for development of AMD. Moreover, AhR−/− mice exhibit decreased visual function and develop dry AMD-like pathology, including disrupted RPE cell tight junctions, accumulation of RPE cell lipofuscin, basal laminar and linear-like deposit material, Bruch’s membrane thickening, and progressive RPE and choroidal atrophy. High-serum low-density lipoprotein levels were also observed in AhR−/− mice. In its oxidized form, this lipoprotein can stimulate increased secretion of extracellular matrix molecules commonly found in deposits from RPE cells, in an AhR-dependent manner. This study demonstrates the importance of cellular clearance via the AhR signaling pathway in dry AMD pathogenesis, implicating AhR as a potential target, and the mouse model as a useful platform for validating future therapies. PMID:24106308

  20. Cone visual pigments.

    PubMed

    Imamoto, Yasushi; Shichida, Yoshinori

    2014-05-01

    Cone visual pigments are visual opsins that are present in vertebrate cone photoreceptor cells and act as photoreceptor molecules responsible for photopic vision. Like the rod visual pigment rhodopsin, which is responsible for scotopic vision, cone visual pigments contain the chromophore 11-cis-retinal, which undergoes cis-trans isomerization resulting in the induction of conformational changes of the protein moiety to form a G protein-activating state. There are multiple types of cone visual pigments with different absorption maxima, which are the molecular basis of color discrimination in animals. Cone visual pigments form a phylogenetic sister group with non-visual opsin groups such as pinopsin, VA opsin, parapinopsin and parietopsin groups. Cone visual pigments diverged into four groups with different absorption maxima, and the rhodopsin group diverged from one of the four groups of cone visual pigments. The photochemical behavior of cone visual pigments is similar to that of pinopsin but considerably different from those of other non-visual opsins. G protein activation efficiency of cone visual pigments is also comparable to that of pinopsin but higher than that of the other non-visual opsins. Recent measurements with sufficient time-resolution demonstrated that G protein activation efficiency of cone visual pigments is lower than that of rhodopsin, which is one of the molecular bases for the lower amplification of cones compared to rods. In this review, the uniqueness of cone visual pigments is shown by comparison of their molecular properties with those of non-visual opsins and rhodopsin. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks. PMID:24021171

  1. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... Vision Around Blind Spot Sep 29, 2015 Could Stem Cells Cure Blindness Caused by Macular Degeneration? Sep 29, ... Contact Us About the Academy Jobs at the Academy Financial Relationships with Industry Medical ...

  2. 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

  3. [Physical activity benefits patients with age-related macular degeneration].

    PubMed

    Subhi, Yousif; Munch, Inger Christine; Singh, Amardeep; Sørensen, Torben Lykke

    2015-08-17

    We have reviewed studies investigating the effect of physical activity on prevention of early age-related macular degeneration (AMD), progression to late AMD, and risk modulation of morbidity and mortality in patients with AMD. Regular physical activity may lower risk of developing early AMD and progression of early AMD to late AMD at a level comparable with smoking cessation or dietary supplements. Studies suggest that AMD itself is associated with physical inactivity which can result in higher morbidity levels. Patients with AMD may benefit from physical activity counselling at all stages of the disease. PMID:26561660

  4. Remote sensing of vegetation based on band-spectral and hyperspectral studies at canopy and pigment level within visible range of wavelength

    NASA Astrophysics Data System (ADS)

    RayChaudhuri, Barun; Bhaumik, Subarnarekha

    2006-12-01

    The suitability of visible spectral response of vegetation for remote sensing has been investigated with field and laboratory studies on canopy and chloroplastidial pigments, respectively. To simulate band-spectral and hyperspectral sensing, measurements were taken both in wavebands and with fine resolution of wavelength. Vegetation species and maturity stages were distinguished with average reflectance and characteristic absorption features. The methodology was tried on both land vegetation, viz. jute canopy of West Bengal and marine plant, viz. green algae of the eastern coast of India. The absorbance variation within visible wavelength range was observed with both mixed chlorophyll solution and solutions of chromatographically separated pigments. The different characteristic absorption peaks were identified, which were quite different for higher plants and algae. The gradual changes in spectral response of leaf pigments with senescence in a common higher plant were systematically investigated with both original leaf extracts and artificial mixtures of fresh and decomposed chlorophyll solutions at different ratios. Mathematical models were put forward for both average and hyperspectral absorption features to track the experimental plots and estimate absorption at different wavelengths.

  5. 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 the biological limits of therapeutic interventions. To optimally benefit from high-resolution multi-modal imaging, an integrated analysis of all functional and structural features is required involving reliable automated algorithms and computational data analyses. Using innovative analysis methods, retinal biomarkers can be used to provide efficient personalized therapy for the individual patient, predictive disease- and population-based models for large-scale management and identifying promising targets for the development of novel therapeutic strategies. PMID:26307399

  6. 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

  7. Skin pigmentation enhancers.

    PubMed

    Brown, D A

    2001-10-01

    The highest incidences of cancer are found in the skin, but endogenous pigmentation is associated with markedly reduced risk. Agents that enhance skin pigmentation have the potential to reduce both photodamage and skin cancer incidence. The purpose of this review is to evaluate agents that have the potential to increase skin pigmentation. These include topically applied substances that simulate natural pigmentation: dihydroxyacetone and melanins; and substances that stimulate the natural pigmentation process: psoralens with UVA (PUVA), dimethylsulfoxide (DMSO), L-tyrosine, L-Dopa, lysosomotropic agents, diacylglycerols, thymidine dinucleotides, DNA fragments, melanocyte stimulating hormone (MSH) analogs, 3-isobutyl-1-methylxanthine (IBMX), nitric oxide donors, and bicyclic monoterpene (BMT) diols. These agents are compared with regards to efficacy when administered to melanoma cells, normal human epidermal melanocytes, animal skin, and human skin. In addition, mechanisms of action are reviewed since these may reveal issues related to both efficacy and safety. Both dihydroxyacetone and topically applied melanins are presently available to the consumer, and both of these have been shown to provide some photoprotection. Of the pigmentation stimulators, only PUVA and MSH analogs have been tested extensively on humans, but there are concerns about the safety and side effects of both. At least some of the remaining pigmentation stimulators under development have the potential to safely induce a photoprotective tan. PMID:11684462

  8. [Microbial sources of pigments].

    PubMed

    Cañizares-Villanueva, R O; Ríos-Leal, E; Olvera Ramírez, R; Ponce Noyola, T; Márquez Rocha, F

    1998-01-01

    Pigments from natural sources has been obtained since long time ago, and their interest has increased due to the toxicity problems caused by those of synthetic origin. In this way the pigments from microbial sources are a good alternative. Some of more important natural pigments, are the carotenoids, flavonoids (anthocyanins) and some tetrapirroles (chloropyls, phycobilliproteins). Another group less important are the betalains and quinones. The carotenoids are molecules formed by isoprenoids units and the most important used as colorant are the alpha and beta carotene which are precursors of vitamin A, and some xantophylls as astaxanthin. The pigment more used in the industry is the beta-carotene which is obtained from some microalgae and cyanobacteria. The astaxanthin another important carotenoid is a red pigment of great commercial value, and it is used in the pharmaceutical feed and acuaculture industries. This pigments is mainly obtained from Phaffia rhodozyma and Haematococcus pluvialis and other organisms. The phycobilliproteins obtained from cyanobacteria and some group of algae, have recently been increased on the food industries. In the last years it has been used as fluorescent marker in biochemical assays. Our research group have carried out studies about the factors that improve the production of these pigments obtained from different microbial species as well as the methods for their extraction and application. PMID:10932737

  9. 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

  10. High-Dose Statins May Ease Macular Degeneration for Some

    MedlinePlus

    ... fullstory_157084.html High-Dose Statins May Ease Macular Degeneration for Some The 'dry' form of the eye ... help people with a common eye disease called macular degeneration, a small study suggests. In the early stage ...

  11. Benign pigmented lesions.

    PubMed

    Bogdan Allemann, Inja; Goldberg, David J

    2011-01-01

    Benign pigmented lesions are a frequent complaint in dermatological patients, especially those seeking advice and therapy in a laser or cosmetic practice. Significant advances in laser technology over the last decades now allow us to effectively and safely treat various benign pigmented lesions. However, a thorough understanding of the biology of the lesion to be treated, the physical properties of the lasers to be used, and laser-tissue interactions is crucial for a successful and safe treatment. This chapter will give an overview of the types of benign pigmented lesions that can be treated with lasers and the specific lasers used to treat them. PMID:21865801

  12. 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

  13. Age-related macular degeneration and changes in the extracellular matrix

    PubMed Central

    Nita, Małgorzata; Strzałka-Mrozik, Barbara; Grzybowski, Andrzej; Mazurek, Urszula; Romaniuk, Wanda

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of permanent, irreversible, central blindness (scotoma in the central visual field that makes reading and writing impossible, stereoscopic vision, recognition of colors and details) in patients over the age of 50 years in European and North America countries, and an important role is attributed to disorders in the regulation of the extracellular matrix (ECM). The main aim of this article is to present the crucial processes that occur on the level of Bruch’s membrane, with special consideration of the metalloproteinase substrates, metalloproteinase, and tissue inhibitor of metalloproteinase (TIMP). A comprehensive review of the literature was performed through MEDLINE and PubMed searches, covering the years 2005–2012, using the following keywords: AMD, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases, Bruch’s membrane, collagen, elastin. In the pathogenesis of AMD, a significant role is played by collagen type I and type IV; elastin; fibulin-3, -5, and -6; matrix metalloproteinase (MMP)-2, MMP-9, MMP-14, and MMP-1; and TIMP-3. Other important mechanisms include: ARMS2 and HTR1 proteins, the complement system, the urokinase plasminogen activator system, and pro-renin receptor activation. Continuous rebuilding of the extracellular matrix occurs in both early and advanced AMD, simultaneously with the dysfunction of retinal pigment epithelium (RPE) cells and endothelial cells. The pathological degradation or accumulation of ECM structural components are caused by impairment or hyperactivity of specific MMPs/TIMPs complexes, and is also endangered by the influence of other mechanisms connected with both genetic and environmental factors. PMID:24938626

  14. Relationship between RPE and choriocapillaris in age-related macular degeneration

    PubMed Central

    McLeod, D. Scott; Grebe, Rhonda; Bhutto, Imran; Merges, Carol; Baba, Takayuki; Lutty, Gerard A.

    2016-01-01

    Purpose The purpose of this study was to examine the relationships between choriocapillaris (CC) and retinal pigment epithelial (RPE) changes in age-related macular degeneration (AMD). Morphological changes in the RPE/choriocapillaris complex were quantified in dry and wet forms of AMD and the results compared to with aged control eyes without maculopathy. Methods Postmortem choroids from 3 aged control subjects, 5 geographic atrophy (GA) subjects and 3 wet AMD subjects were analyzed using a semi-quantitative computer-assisted morphometric technique developed to measure percent RPE and CC areas in choroidal whole mounts incubated for alkaline phosphatase activity. The tissues were subsequently embedded in methacrylate and sectioned to examine structural changes. Results There was a linear relationship between the loss of RPE and CC in GA. A 50% reduction in vascular area was found in regions of complete RPE atrophy. Extreme constriction of remaining viable capillaries was found in areas devoid of RPE. Adjacent to active choroidal neovascularization (CNV) in wet AMD, CC dropout was evident in the absence of RPE atrophy resulting in a 50% decrease in vascular area. Lumenal diameters of the remaining capillaries in wet AMD eyes were similar to controls. Conclusions The primary insult in GA appears to be at the level of the RPE and there is an intimate relationship between RPE atrophy and secondary CC degeneration. CC degeneration occurs in the presence of viable RPE in wet AMD. The RPE in regions of vascular dropout are presumably hypoxic, which may result in an increase in VEGF production by the RPE and stimulation of CNV. PMID:19357355

  15. 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

  16. 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.

  17. Macular Infarction Associated with Reactive Arthritis

    PubMed Central

    Kim, Ju-Young; Lee, Jong-Hyuck

    2010-01-01

    A 53-year-old woman visited the Department of Rheumatology with a chief complaint of a 3-day history of fever and chills and also presented with pain occuring in both knees at the time of outpatient visit. Based on rheumatologic and hematological lab studies, ultrasonography, and a needle aspiration biopsy of the articular cavity, the patient was diagnosed with reactive arthritis. On hospitalization day 3, consultation with the Department of Ophthalmology was requested regarding decreased visual acuity lasting for 3 days. Upon ophthalmologic examination, the corrected visual acuity was 0.1 in the right eye and 0.05 in the left eye. Upon slit lamp microscopy, there were no abnormal findings in the anterior segment. Upon fundus examination, however, there were yellow-white lesions in the macular area of both eyes. Fluorescein angiographywas performed to assess the macular lesions, and the findings were suggestive of macular infarction in both eyes. Due to a lack of other underlying disease, a past surgical history, and a past history of drug administration, the patient was diagnosed with macular infarction in both eyes associated with reactive arthritis. To date, there have been no other such cases reported. In a patient with reactive arthritis, we experienced a case of macular infarction in both eyes, which occurred without association with a past history of specific drug use or underlying disease. Herein, we report our case, with a review of the literature. PMID:21052513

  18. [Truss-induced macular amyloidosis].

    PubMed

    Abels, C; Karrer, S; Landthaler, M; Szeimies, R M

    2001-10-01

    A 80-year-old male presented with a long time history of a localized red-brown macule with superficial lichenification and slight scaling in the right groin. An earlier skin biopsy revealed the presence of amyloid deposits. The patient therefore had a complete internal checkup including a rectal biopsy for exclusion of systemic amyloidosis. However, the laboratory data did not reveal any specific abnormalities including immunoglobulins and Bence-Jones protein. The rectal biopsy was also nonspecific. After skin examination, a rebiopsy was performed at our department showing acanthosis and spongiosis of the epidermis with parakeratosis. A homogenous eosinophilic deposit was present in the upper dermis and stained positive with thioflavine. At the second visit the patient wore a truss for a right inguinal hernia, perfectly matching the area of the skin lesion. Thus, the diagnosis of a localized macular amyloidosis was confirmed very likely due to permanent local friction. The classification of localized cutaneous amyloidoses should include local trauma as a cause to avoid unnecessary and exhausting internal checkups to exclude systemic involvement. PMID:11715396

  19. 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

  20. Diabetic macular edema: New promising therapies

    PubMed Central

    Shamsi, Hanan N Al; Masaud, Jluwi S; Ghazi, Nicola G

    2013-01-01

    The treatment of diabetic macular edema is rapidly evolving. The era of laser therapy is being quickly replaced by an era of pharmacotherapy. Several pharmacotherapies have been recently developed for the treatment of retinal vascular diseases such as diabetic macular edema. Several intravitreal injections or sustained delivery devices have undergone phase 3 testing while others are currently being evaluated. The results of clinical trials have shown the superiority of some of these agents to laser therapy. However, with the availability of several of these newer agents, it may be difficult to individualize treatment options especially those patients respond differently to various therapies. As such, more effort is still needed in order to determine the best treatment regimen for a given patient. In this article, we briefly summarize the major new therapeutic additions for the treatment of diabetic macular edema and allude to some future promising therapies. PMID:24379924

  1. Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin.

    PubMed

    Sprecher, E; Bergman, R; Richard, G; Lurie, R; Shalev, S; Petronius, D; Shalata, A; Anbinder, Y; Leibu, R; Perlman, I; Cohen, N; Szargel, R

    2001-10-01

    Congenital hypotrichosis associated with juvenile macular dystrophy (HJMD; MIM601553) is an autosomal recessive disorder of unknown etiology, characterized by hair loss heralding progressive macular degeneration and early blindness. We used homozygosity mapping in four consanguineous families to localize the gene defective in HJMD to 16q22.1. This region contains CDH3, encoding P-cadherin, which is expressed in the retinal pigment epithelium and hair follicles. Mutation analysis shows in all families a common homozygous deletion in exon 8 of CDH3. These results establish the molecular etiology of HJMD and implicate for the first time a cadherin molecule in the pathogenesis of a human hair and retinal disorder. PMID:11544476

  2. 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. PMID:23676239

  3. Macular star formation in diabetic patients with non-arteritic anterior ischemic optic neuropathy (NA-AION)

    PubMed Central

    Galvez-Ruiz, Alberto

    2014-01-01

    Background NA-AION is a condition that exhibits a number of unique characteristics in diabetics compared with the rest of the population. In some diabetic patients with NA-AION, lipid deposits can be observed around the macula forming an incomplete macular star. Methods We describe 12 case studies of patients with NA-AION observing the development of lipid deposits around the macula forming an incomplete macular star. Results All our patients developed some level of lipid deposits around the macula in the form of a macular hemistar in the course of their illness. Conclusion Some authors have suggested that the macular star is formed by transudation from capillaries deep in the optic disk through the intermediary tissue of Kuhnt, which is located between the retina and the anterior portion of the lamina retinalis. However, the development of the macular star is currently understood not as a simple transudation but as a multifactorial process involving the presence of vascular damage around the optic disk, which is considered one of the most important factors leading to its occurrence. Although some studies mention the presence of a macular star in patients with NA-AION, we believe that this phenomenon may be significantly more common than the current literature suggests. PMID:25859144

  4. Cellular models and therapies for age-related macular degeneration

    PubMed Central

    Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

    2015-01-01

    ABSTRACT Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD). A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease. PMID:26035859

  5. Structural Changes in Individual Retinal Layers in Diabetic Macular Edema

    PubMed Central

    Yoshimura, Nagahisa

    2013-01-01

    Optical coherence tomography (OCT) has enabled objective measurement of the total retinal thickness in diabetic macular edema (DME). The central retinal thickness is correlated modestly with visual impairment and changes paradoxically after treatments compared to the visual acuity. This suggests the clinical relevance of the central retinal thickness in DME and the presence of other factors that affect visual disturbance. Recent advances in spectral-domain (SD) OCT have provided better delineation of the structural changes and fine lesions in the individual retinal layers. Cystoid spaces in the inner nuclear layer and outer plexiform layer are related to quantitative and qualitative parameters in fluorescein angiography. OCT often shows vitreoretinal interface abnormalities in eyes with sponge-like retinal swelling. Serous retinal detachment is sometimes accompanied by hyperreflective foci in the subretinal fluid, which exacerbates the pathogenesis at the interface of the photoreceptors and retinal pigment epithelium. Photoreceptor damage at the fovea is thought to be represented by disruption of the external limiting membrane or the junction between the inner and outer segment lines and is correlated with visual impairment. Hyperreflective foci in the outer retinal layers on SD-OCT images, another marker of visual disturbance, are associated with foveal photoreceptor damage. PMID:24073417

  6. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. PMID:23580402

  7. Toxicity and detoxification of lipid-derived aldehydes in cultured retinal pigmented epithelial cells.

    PubMed

    Choudhary, S; Xiao, T; Srivastava, S; Zhang, W; Chan, L L; Vergara, L A; Van Kuijk, F J G M; Ansari, N H

    2005-04-15

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the developed world and yet its pathogenesis remains poorly understood. Retina has high levels of polyunsaturated fatty acids (PUFAs) and functions under conditions of oxidative stress. To investigate whether peroxidative products of PUFAs induce apoptosis in retinal pigmented epithelial (RPE) cells and possibly contribute to ARMD, human retinal pigmented epithelial cells (ARPE-19) were exposed to micromolar concentrations of H2O2, 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE). A concentration- and time-dependent increase in H2O2-, HNE-, and HHE-induced apoptosis was observed when monitored by quantifying DNA fragmentation as determined by ELISA, flow cytometry, and Hoechst staining. The broad-spectrum inhibitor of apoptosis Z-VAD inhibited apoptosis. Treatment of RPE cells with a thionein peptide prior to exposure to H2O2 or HNE reduced the formation of protein-HNE adducts as well as alteration in mitochondrial membrane potential and apoptosis. Using 3H-HNE, various metabolic pathways to detoxify HNE by ARPE-19 cells were studied. The metabolites were separated by HPLC and characterized by ElectroSpray Ionization-Mass Spectrometry (ESI-MS) and gas chromatography-MS. Three main metabolic routes of HNE detoxification were detected: (1) conjugation with glutathione (GSH) to form GS-HNE, catalyzed by glutathione-S-transferase (GST), (2) reduction of GS-HNE catalyzed by aldose reductase, and (3) oxidation of HNE catalyzed by aldehyde dehydrogenase (ALDH). Preventing HNE formation by a combined strategy of antioxidants, scavenging HNE by thionein peptide, and inhibiting apoptosis by caspase inhibitors may offer a potential therapy to limit retinal degeneration in ARMD. PMID:15808518

  8. Disorders of pigmentation.

    PubMed

    Fistarol, Susanna K; Itin, Peter H

    2010-03-01

    Skin color is highly individual and the variations are controlled by numerous genes. The different skin colors result from the size and number of melanosomes and do not mirror the amount of melanocytes. Disorders of pigmentation can result from migration abnormalities of melanocytes from the neural crest to the skin during embryogenesis. In addition, impairment of melanosome transfer to the surrounding keratinocytes, an alteration in melanin synthesis and a defective degradation or removal of melanin may lead to abnormal skin pigmentation. Immunologic or toxic mediated destructions of melanocytes can end in pigmentation disorders. Disorders of pigmentation are classified in hypo- or hyperpigmentation which can occur as a genetic or acquired disease. They can manifest locally or diffuse. Congenital hypopigmentation can be restricted to the skin as in piebaldism or they represent a systemic disease as in Menkes disease or phenylketonuria. Localized hypo- or hyperpigmentation in children may serve as markers for systemic diseases. Ash-leaf hypopigmentation are characteristic for tuberous sclerosis and more than 5 café-au-lait spots suggest neurofibromatosis 1 (von Recklinghausen disease). The most common autoimmune-induced depigmentation is vitiligo. Generalized hyperpigmentation only rarely reflects a primary genetic disorder but is most often from acquired diseases as in Addison disease, secondary hemochromatosis or primary biliary cirrhosis. Treatment of pigmentation disorders are based on a diagnosis which sometimes allow a specific intervention. Cosmetically acceptable results are difficult to obtain. PMID:19788584

  9. The role of epigenetics in age-related macular degeneration.

    PubMed

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the headlines 'DNA methylation in age related macular degeneration', 'altered gene expression in AMD pathogenesis'. A manual search was also based on references from these articles as well as review articles. PMID:25233816

  10. Ascorbic acid repletion: A possible therapy for diabetic macular edema?

    PubMed

    May, James M

    2016-05-01

    Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose-induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-ĸB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema. PMID:26898503

  11. Study of 27 Aqueous Humor Cytokines in Type 2 Diabetic Patients with or without Macular Edema

    PubMed Central

    Dong, Ning; Xu, Bing; Chu, Liqun; Tang, Xin

    2015-01-01

    The aim of the present study was to compare the changes in the levels of 27 aqueous humor cytokines between diabetic patients with macular edema (ME) and diabetic patients without ME. Undiluted aqueous humor samples were obtained from 68 consecutive type 2 diabetic patients without ME and 56 consecutive type 2 diabetic patients with ME. The concentrations of 27 cytokines in the aqueous humor samples were measured using a multiplex bead immunoassay. Compared with diabetic patients without ME, diabetic patients with ME had significantly higher concentrations of IL-1β, IL-6, IL-8, IP-10, MCP-1, and VEGF in the aqueous humor. However, the concentrations of IL-10 and IL-12 were significantly lower in the diabetic patients with ME. The aqueous humor levels of IL-1β, IL-6, IL-8, MCP-1, IP-10, and VEGF were closely correlated with retinal macular thickness, retinal macular volume and the severity of ME. In addition, the aqueous humor levels of IL-10 and IL-12 decreased with increasing the severity of ME. A variety of cytokines associated with inflammation and angiogenesis may contribute to the pathogenesis of diabetic macular edema, and both anti-inflammatory and antiangiogenic agents should be included in the treatment of ME simultaneously. PMID:25923230

  12. Pathological Consequences of Long-Term Mitochondrial Oxidative Stress in the Mouse Retinal Pigment Epithelium

    PubMed Central

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

    2012-01-01

    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 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. PMID:22687918

  13. Controlling Retinal Pigment Epithelial Cell Patch Size Influences Growth Factor Expression

    SciTech Connect

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

    2014-01-01

    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. 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.

  14. Controlling Retinal Pigment Epithelial Cell Patch Size Influences Growth Factor Expression

    DOE PAGESBeta

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

    2014-01-01

    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. 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

  15. Apr3 accelerates the senescence of human retinal pigment epithelial cells.

    PubMed

    Han, Song; Lu, Qingjun; Wang, Ningli

    2016-04-01

    Senescence of retinal pigment epithelium (RPE) cells is a major contributor to age‑related macular degeneration (AMD). However, the molecular mechanisms underlying RPE dysfunction are not well understood. Apoptosis related protein 3 (Apr3) was originally cloned from HL‑60 cells induced by all‑trans retinoic acid (ATRA). Preliminary data revealed elevated Apr3 expression in the tissues of aged mice, suggesting that it is involved in the aging process. The present study demonstrated that Apr3 mRNA and protein levels were markedly increased in aged mouse RPE cells. Elevated Apr3 expression was also observed during premature senescence induced by oxidative stress (H2O2 and tert‑BHP) in ARPE‑19 cells. Moreover, Apr3 overexpression promoted cellular senescence in ARPE‑19 cells, as characterized by enhanced senescence‑associated β‑galactosidase activity, reduced cell proliferation and increased expression of the senescence markers p53 and p21. In addition, it was demonstrated that overexpression of Apr3‑N, a truncated counterpart of Apr3, abrogated Apr3‑induced phenotypes. It was concluded that Apr3 expression was induced in replicative and premature senescence of RPE cells and its overexpression accelerated senescence of ARPE‑19 cells, which provides important insights into the function of Apr3 in senescence‑associated diseases. PMID:26934949

  16. 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

  17. Fuzzy logic for identifying pigments studied by Raman spectroscopy.

    PubMed

    Ramos, Pablo Manuel; Ferré, Joan; Ruisánchez, Itziar; Andrikopoulos, Konstantinos S

    2004-07-01

    Fuzzy logic and linguistic variables are used for the automatic interpretation of Raman spectra obtained from pigments found in cultural heritage art objects. Featured bands are extracted from a Raman spectrum of a reference pigment and the methodology for constructing the library is illustrated. An unknown spectrum is then interpreted automatically and a process for identifying the corresponding pigment is described. A reference library consisting of 32 pigments was built and the effectiveness of the algorithm was tested by the Raman spectroscopic analysis of 10 pigments that are known to have been extensively used in Byzantine hagiography. Binary mixtures of these pigments were also tested. The algorithm's level of identification was good even though extra peaks, noise, and background signals were encountered in the spectra. PMID:15282052

  18. 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.

  19. 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,…

  20. 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…

  1. Current status in diabetic macular edema treatments.

    PubMed

    Romero-Aroca, Pedro

    2013-10-15

    Diabetes is a serious chronic condition, which increase the risk of cardiovascular diseases, kidney failure and nerve damage leading to amputation. Furthermore the ocular complications include diabetic macular edema, is the leading cause of blindness among adults in the industrialized countries. Today, blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy. The treatment should include an optimized control of glycemia, arterial tension, lipids and renal status. The photocoagulation laser is currently restricted to focal macular edema in some countries, but due the high cost of intravitreal drugs, the use of laser treatment for focal and diffuse diabetic macular edema (DME), can be valid as gold standard in many countries. The intravitreal anti vascular endothelial growth factor drugs (ranibizumab and bevacizumab), are indicated in the treatment of all types of DME, but the correct protocol for administration should be defined for the different Retina Scientific Societies. The corticosteroids for diffuse DME, has a place in pseudophakic patients, but its complications restricted the use of these drugs for some patients. Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients. PMID:24147200

  2. Driving and Age-Related Macular Degeneration

    PubMed Central

    Owsley, Cynthia; McGwin, Gerald

    2009-01-01

    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, and considers directions for future research. PMID:20046818

  3. 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

  4. Genetics Home Reference: Stargardt macular degeneration

    MedlinePlus

    ... 004. Epub 2009 Feb 20. Review. Walia S, Fishman GA. Natural history of phenotypic changes in Stargardt macular dystrophy. ... May 25, 2016 The resources on this site should not be used as a substitute for professional medical care or advice. Users with ...

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

    PubMed Central

    Chen, Mei; Xu, Heping

    2016-01-01

    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 due to its unique anatomical and physiological 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, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), 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 AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

  6. 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.

  7. 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. PMID:17177553

  8. 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)

  9. Scotopic Microperimetry in the Early Diagnosis of Age-Related Macular Degeneration: Preliminary Study

    PubMed Central

    Pescosolido, Nicola

    2014-01-01

    Background. Recent clinical studies have shown that, in some degenerative retinal diseases, like age-related macular degeneration (AMD), the sensitivity of the rods decreases more rapidly than the sensitivity of the cones. The aim of this study was to evaluate if there is a correlation between the presence of hard drusen at the macular level and the rod damage responsible for the reduction in scotopic retinal sensitivity in subjects at risk for AMD. Methods. The authors selected 24 subjects (14 men and 10 women) with an average age of 67.25 ± 5.7 years. Macular hard drusen were present in 50% of the subjects at the fundus oculi exam. The researchers evaluated the retinal sensitivity to light in mesopic and scotopic conditions of each subject with an MP-1 scotopic microperimeter (MP-1S). Results. In subjects with hard drusen in the fundus oculi examination, there was a statistically significant reduction in scotopic retinal sensitivity, while the mesopic retinal sensitivity was not compromised. Conclusion. This study revealed how the presence of hard drusen at the macular level is associated with a reduction in scotopic retinal sensitivity compared to a control group of healthy subjects. Retinal functionality in a scotopic setting examined with MP-1S could be useful in early diagnosis of AMD. PMID:25548774

  10. 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…

  11. 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

  12. 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

  13. Lipofuscin in the retina: quantitative assay for an unprecedented autofluorescent compound (pyridinium bis-retinoid, A2-E) of ocular age pigment.

    PubMed

    Reinboth, J J; Gautschi, K; Munz, K; Eldred, G E; Remé, C E

    1997-11-01

    The pyridinium bis-retinoid, A2-E, has been discovered as one of the major autofluorescent components of retinal pigment epithelial lipofuscin. Due to its chemical characteristics, A2-E may contribute to cellular and molecular changes leading to age-related macular degeneration. Because A2-E is the first lipofuscin component that has been identified, purified, and its structure analysed, it represents an important marker molecule for studying lipofuscin formation under various conditions. In order to investigate the role of A2-E in ageing processes of the retinal pigment epithelium, we developed an HPLC assay for this compound using single wavelength UV-absorbance detection with continuous light emission. Standard A2-E was synthetized and purified by sequential TLC. In our assay, A2-E can be detected in amounts lower than 10 pmol. The assay has been applied to quantitative determination of A2-E amounts in albino rat eyes of different age groups. Our results demonstrate that there is a marked increase of A2-E levels in older animals. The method described is the first to allow quantification of this unusual retinoid from small amounts of biological samples. PMID:9367643

  14. 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

  15. 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. PMID:27019785

  16. Bilateral macular dysplasia ('colobomata') and congenital retinal dystrophy.

    PubMed Central

    Moore, A T; Taylor, D S; Harden, A

    1985-01-01

    Three unrelated patients with bilateral macular dysplasia ('colobomata') with no relevant family history were found to have absent or substantially abnormal electroretinograms, implying that there was an associated retinal dystrophy. This may suggest that the macular lesions are associated with a global failure of retinal development, with a regional preponderance rather than a purely localised cause such as an intrauterine infection. It is important to distinguish between congenital infections such as toxoplasmosis and developmental macular colobomata, which have a somewhat similar ophthalmoscopic appearance as a cause of bilateral macular abnormalities seen in young children, since they have different implications for genetic advice and future ophthalmic care. Images PMID:4041416

  17. 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. PMID:25438734

  18. 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

  19. Emerging Pharmacotherapies for Diabetic Macular Edema

    PubMed Central

    Javey, Golnaz; Schwartz, Stephen G.; Flynn, Harry W.

    2012-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss in patients with diabetes mellitus. Although photocoagulation and intensive control of systemic metabolic factors have been reported to achieve improved outcomes in large randomized clinical trials (RCTs), some patients with DME continue to lose vision despite treatment. Pharmacotherapies for DME include locally and systemically administered agents. We review several agents that have been studied for the treatment of DME. PMID:22474425

  20. 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

  1. 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

  2. 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.

  3. Peroxisome Proliferator-Activated Receptor and Age-Related Macular Degeneration

    PubMed Central

    Herzlich, Alexandra A.; Tuo, Jingsheng; Chan, Chi-Chao

    2008-01-01

    Age-related macular degeneration (AMD) is the leading cause of new blindness in the western world and is becoming more of a socio-medical problem as the proportion of the aged population increases. There are multiple efforts underway to better understand this disease process. AMD involves the abnormal retinal pigment epithelium (RPE), drusen formation, photoreceptor atrophy, and choroidal neovascularization. Peroxisome proliferator-activated receptors (PPARs) play an important role in lipid degeneration, immune regulation, regulation of reactive oxygen species (ROSs), as well as regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and docosahexaenoic acid (DHA). These molecules have all been implicated in the pathogenesis of AMD. In addition, PPAR gamma is expressed in RPE, an essential cell in photoreceptor regeneration and vision maintenance. This review summarizes the interactions between PPAR, AMD-related molecules, and AMD-related disease processes. PMID:18288287

  4. 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

  5. Stem cell-based therapies for age-related macular degeneration: current status and prospects

    PubMed Central

    Mu, Yalin; Zhao, Manli; Su, Guangming

    2014-01-01

    Abstract: Age-related macular degeneration (AMD) is one of the major causes of irreversible blindness both in developed and developing countries. During the past decades, the managements of neovascular AMD (wet AMD) have dramatically progressed. However, still no effective treatment for non-neovascular AMD (dry AMD) which was characterized by geographic macular atrophy. Recent advances in stem cell sciences have demonstrated that retinal pigment epithelium (RPE) cells can be generated from several types of stem cells (including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, et al) by cell co-culturing or defined factors. Additionally, studies also showed that visual function could be recovered by transplantation of these cells into subretinal space in vivo. Moreover, the United States Food and Drug Administration already approved several clinical trials to evaluate the efficiencies of stem cell based cell transplantation for dry AMD patients. Till now, a few patients enrolled in these studies achieved promising outcomes. This review will summarize recent advances in stem cell based RPE differentiation, transplantation, and the preliminary results of clinical trials. The obstacles and prospects in this field will also be discussed. PMID:25550892

  6. Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.

    PubMed

    Wei, Cynthia X; Sun, Aixu; Yu, Ying; Liu, Qianyong; Tan, Yue-Qing; Tachibana, Isamu; Zeng, Hong; Wei, Ji-Ye

    2016-01-01

    Dry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD. PMID:26427400

  7. Basis for enhanced barrier function of pigmented skin.

    PubMed

    Man, Mao-Qiang; Lin, Tzu-Kai; Santiago, Juan L; 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

    2014-09-01

    Humans with darkly pigmented skin display superior permeability barrier function in comparison with 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 (nonpigmented) versus 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 versus SKH1 mice, correlating with a reduced pH in the lower SC that colocalizes 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 reacidification 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 human keratinocytes display enhanced barrier function in comparison with 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

  8. 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

  9. Pigment cells and pigment cell tumors in fish.

    PubMed

    Masahito, P; Ishikawa, T; Sugano, H

    1989-05-01

    The three basic pigment cell types found in poikilothermic vertebrates, melanocytes (melanin-producing cells), erythrophores (red or yellow pigment cells), and iridophores (iridescence-producing cells), are derived from neural crest. Neoplasms of pigment cells in fish are also of three phenotypes, melanomas (melanophoromas), erythrophoromas, and iridophoromas, showing the phenotypes of their corresponding normal pigment cells. These pigment cell tumors are among the most common types in bony fish and seem to be more common in fish than in mammals, including humans. Moreover, there are no mammalian neoplasms corresponding to erythrophoromas and iridophoromas in fish. The complexities in the nature and classification of pigment cell tumors in fish will be discussed on the basis of a survey of our collection of these tumors at the Cancer Institute. The etiology of pigment cell tumors in fish is obscure. In order to know whether activated oncogene is involved in the genesis of erythrophoromas in goldfish, the ras genes from normal and erythrophoroma cells were cloned and their nucleotide sequences were compared. The goldfish ras gene and human ras genes showed striking homology. However, no point mutation at the 12th codon was observed in ras genes isolated from erythrophoromas. Besides pigment cell tumors in fish, abnormal pigmentation or depigmentation in flounders associated with diseased conditions is also described. PMID:2654300

  10. [Synthesis of melanin pigments by Antarctic black yeast].

    PubMed

    Tashirev, A B; Romanovskaia, V A; Rokitko, P V; Matveeva, N A; Shilin, S O; Tashireva, A A

    2012-01-01

    Five strains of the black yeast similar to Exophiala nigra (Nadsoniela nigra), which we have isolated from the Antarctic biotopes, are studied. At cultivation in a periodic operation the maximum level of absolutely dry biomass in five tested strains constituted 3.2-7.8 g/l of medium, melanin pigment yield being 6-9% of absolutely dry mass of cells. Two highly productive strains have been selected. Pigments of the studied black yeast are water-insoluble, however dissolve in alkali and concentrated acids. The maximum absorption of the yeast pigments was in the range of 220 nm. The above-stated properties of pigments of the investigated yeast correspond to the description of melanin fractions of Nadsoniela nigra and some microscopic mushrooms. The water-soluble melanin-pigments have been obtained after the dialysis of alkaline solution of the pigment. UV-spectra and visible absorption spectra of water solution of melanin-pigments are almost identical to those of initial alkaline solutions. It is shown that the studied yeast are resistant to high concentrations of toxic metals (Hg2+, Cu2+, Co2+, Cr(VI) and Ni2+), and introduction of Co2+ into the cultivation medium leads to the increase of pigments synthesis. PMID:23120979

  11. Bilateral Refractive Changes in Vascularized Pigment Epithelial Detachment Treated by Anti-VEGF Therapy

    PubMed Central

    Hanhart, Joel; Chowers, Itay

    2015-01-01

    We report the case of a patient bilaterally treated with anti-VEGF compounds for bilateral massive vascularized retinal pigment epithelial detachment (PED). During the years prior to treatment, PED growth was accompanied by gradual hypermetropization. After right intraocular injection of bevacizumab followed by three bilateral aflibercept injections, the PED flattened resulting in a rapid relative myopization. This case illustrates ocular refractive properties associated with PED and its response to treatment. This case also highlights the importance of assessing refraction in age-related macular degeneration patients experiencing substantial PED amplitude changes. PMID:26955349

  12. The response of human retinal pigmented epithelial cells in vitro to changes in nitric oxide concentration stimulated by low levels of red light

    NASA Astrophysics Data System (ADS)

    Lavey, Brent J.; Estlack, Larry E.; Schuster, Kurt J.; Rockwell, Benjamin A.; Wigle, Jeffrey C.

    2013-03-01

    The goal of this project is to explore the role of nitric oxide (NO) in regulating the response of hTERT-RPE to low-level exposures to red light. Exposure to low-level red light has been shown to positively affect wound healing, reduce pain, and encourage cell proliferation. The current explanation for this effect is described as an interaction between the photons and cytochrome c oxidase (Cco), which plays a role in regulation of intracellular NO levels in addition to being the mitochondrial protein complex where reduction of oxygen occurs in the process of oxidative phosphorylation. Exposure to 2.88 J/cm2 of 671-nm and 637-nm light shows a two-fold increase in NO immediately after exposure, and a 56% increase in ATP measured at ~5 h post exposure. Levels of NF-κB mRNA and protein were measured at six and 24 h, respectively, and found to increase six fold, correlating with increases in NO levels. Light-stimulated increased levels of NO also correlated with an 11-fold increase in Bcl-2 and a 70% decrease in Bax mRNA levels, relative to controls. NF-κB promotes cell growth and Bcl-2 is an apoptosis suppressor protein. Bax is a positive apoptotic effector protein. These results support the hypothesis that light-induced changes in the intracellular levels of NO play a role in the beneficial effects of low-level light photobiomodulation

  13. [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

  14. Macular amyloidosis complicating macroprolactinoma--a novel clinical association.

    PubMed

    Dutta, Deep; Ahuja, Arvind; Sharma, Lokesh; Bhardwaj, Minakshi; Kulshreshtha, Bindu

    2015-01-01

    Amyloid deposition in the pituitary gland is a rare localised form of amyloidosis, and most commonly reported with prolactinoma. Macular amyloidosis is a rare form of localised cutaneous amyloidosis of obscure aetiology. In contrast to most localised amyloidosis, the precursor protein(s) of both macular amyloidosis and prolactinoma are unknown. A 35-year-old man with chronic headache (six years), blurring of vision (three years), and hyperpigmented macular lesion involving arms, legs, and back (two years) was diagnosed to have hyperprolactinaemia (8927 ng/mL) and secondary adrenal insufficiency. MRI revealed pituitary macroadenoma compressing the optic chiasma, encasing the right carotid artery and extending into the sphenoid sinus. A biopsy of skin from the right upper arm revealed thickened stratum corneum, acanthosis, and deposition of pale eosinophilic material in papillary dermis that gave a rose pink colour under methyl-violet and appeared congophilic with Congo red stain, which under polarised light showed green birefringence, diagnostic of macular amyloidosis. Headache, bitemporal haemianopia, and skin lesion improved following cabergoline therapy. Temporal profile of the disease characterised by symptoms of macroprolactinoma preceding onset of macular amyloidosis with resolution of symptoms of macroprolactinoma, accompanied by reductions in prolactin, and concomitant improvement in macular amyloidosis with cabergoline therapy may suggest some link between macroprolactinoma and macular amyloidosis. This report intends to highlight this novel association of macular amyloidosis and macroprolactinoma. PMID:26662655

  15. [Diabetic macular edema--modern diagnostics and treatment].

    PubMed

    Wylegała, Edward; Mańkowski, Wojciech; Pilat, Jarosław; Teper, Sławomir; Skupień-Mańkowska, Hanna

    2010-07-01

    Diabetic macular edema is very important medical and social problem and major cause of severe and permanent visual acuity depression in the working-age population. Rapid diagnostics with optical coherence tomography, color fundus photography, fluorescein angiography and appropriate treatment in patients with diabetes stops or retards progress of diabetic macular edema. PMID:20712253

  16. Pigmentation disorders: hyperpigmentation and hypopigmentation.

    PubMed

    Nicolaidou, Electra; Katsambas, Andreas D

    2014-01-01

    Pigmentation disorders include a large number of heterogeneous conditions that are usually characterized by altered melanocyte density, melanin concentration, or both, and result in altered pigmentation of the skin. Some of these disorders are extremely common (melasma, vitiligo), whereas others are rare. In this contribution, we review the most common pigmentation disorders that appear on the face. These lesions, even though mostly asymptomatic, have a great impact on a patient's quality of life. PMID:24314378

  17. 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

  18. The role of epigenetics in age-related macular degeneration

    PubMed Central

    Gemenetzi, M; Lotery, A J

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: ‘ocular epigenetic mechanisms', ‘human disease epigenetics', and ‘age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was ‘epigenetics in ocular disease', and to restrict search, we used the headlines ‘DNA methylation in age related macular degeneration', ‘altered gene expression in AMD pathogenesis'. A manual search was also based on references from these articles as well as review articles. PMID:25233816

  19. 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

  20. Photooxidative damage in retinal pigment epithelial cells via GRP78 and the protective role of grape skin polyphenols.

    PubMed

    Zhao, Zhao; Sun, Tao; Jiang, Yun; Wu, Lijiang; Cai, Xiangzhong; Sun, Xiaodong; Sun, Xiangjun

    2014-12-01

    Blue light induced oxidative damage and ER stress are related to the pathogenesis of age-related macular degeneration (AMD). However, the mechanism of blue light-induced damage remained obscure. The objective of this work is to assess the photooxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of ER stress associated apoptotic proteins, and investigate the mechanism underlying the protective effects of grape skin extracts. To mimic lipofuscin-mediated photooxidation in vivo, ARPE-19 cells that accumulated A2E, one of lipofuscin fluorophores, were used as a model system to investigate the mechanism of photooxidative damage and the protective effects of grape skin polyphenols. Exposure of A2E containing ARPE-19 cells to blue light resulted in significant apoptosis and increases in levels of GRP78, CHOP, p-JNK, Bax, cleaved caspase-9, and cleaved caspase-3, indicating that photooxidative damage to RPE cells is mediated by the ER-stress-induced intrinsic apoptotic pathway. Cells in which GRP78 had been knocked down with shRNA were more vulnerable to photooxidative damage. Pre-treatment of blue-light-exposed A2E containing ARPE-19 cells, with grape skin extracts, inhibited apoptosis, in a dose dependent manner. Knockdown GRP78 blocked the protective effect of grape skin extracts. PMID:25447759

  1. Health state utilities in patients with diabetic retinopathy, diabetic macular oedema and age-related macular degeneration: a systematic review

    PubMed Central

    2013-01-01

    Background Health state utility values (HSUVs) are important in the assessment of the cost effectiveness of new interventions. In the case of visual conditions, models generally tend have tended to be built around a set of health states defined by visual acuity (VA). The aim of this review was to assess the impact of VA on HSUVs in patients with diabetic retinopathy, diabetic macular oedema or age-related macular degeneration. Methods A systematic literature search was undertaken in major bibliographic databases to identify articles reporting on the relationship between HSUVs and vision. Data were extracted for population characteristics, visual levels and estimated utilities. Evidence from reported statistical models, where available, was considered in the evaluation of vision in the better-seeing eye and the worse-seeing eye. Due to the heterogeneity of included studies, a narrative synthesis was undertaken. Results Of the 17 relevant studies, 9 studies had data that could be used in the analysis of the impact of vision on HSUVs. Visual loss was associated with a marked impact on health utilities. However, the relationship was not comparable between conditions or by measure of HSUVs. Key results included the finding that overall, self-rated time-trade off estimates were more likely to discriminate between different VA levels than EQ-5D values. Additionally, a stronger correlation was observed between HSUVs and better-seeing eye VA compared to worse-seeing eye VA. Conclusions Visual acuity has a significant impact on HSUVs. Nevertheless, care must be taken in the interpretation and use of estimates in cost-effectiveness models due to differences in measures and population diversity. PMID:24304921

  2. Macular laser photocoagulation with or without intravitreal triamcinolone pretreatment for diabetic macular edema: a result from five randomized controlled trials

    PubMed Central

    Liu, Xiang-Dong; Zhou, Xiao-Dong; Wang, Zhi; Shen, Yong-Ming

    2016-01-01

    AIM To assess possible benefits of intravitreal triamcinolone acetonide (IVTA) injection as pretreatment for macular laser photocoagulation (MLP) in patients with diabetic macular edema (DME). METHODS Published randomized controlled trials (RCTs) concerning MLP with or without IVTA pretreatment for DME were retrieved from databases CNKI, Medline, EMbase, Web of Science, and the Cochrane Library. A Meta-analysis on eligible studies was conducted using RevMan 5.0 software. Two investigators independently assessed the quality of the trials and extracted data. Main outcome measures included the change in best corrected visual acuity (BCVA), difference in central macular thickness (CMT) and adverse events reporting in particular elevated intraocular pressure within the follow-up period. The results were pooled using weight mean difference (WMD) or odds risk (OR) with their corresponding 95% confidence intervals (CI). A fixed- or random-effect model was employed depending on the heterogeneity of the inclusion trials. RESULTS Finally, five independent RCTs were identified and used for comparing MLP with IVTA pretreatment (131 eyes) with MLP alone (133 eyes, control group). The overall study quality was relatively higher according to the modified Jadad scale. The Meta-analysis showed that MLP with IVTA pretreatment significantly reduced CMT at one, three and six months (P=0.002, 0.0003 and 0.04, respectively), compared with MLP alone. The IVTA pretreatment group showed statistically significant improvements in BCVA at the one-month follow up as compared with the control group (P=0.03). At three- and six-month follow up, there was a beneficial trend towards improving visual acuity in the IVTA pretreatment group without statistical significance between groups (P=0.06 and 0.20, respectively). The incidence of elevation of intraocular pressure was significantly higher in the IVTA pretreatment group than in the control group (P<0.0001). No evidence of publication bias was present according to Begg's test and Egger's test. There was a low level of heterogeneity in the included studies. CONCLUSION This Meta-analysis indicates that MLP with IVTA pretreatment has a better therapeutic effect in terms of CMT reduction and earlier (1mo) visual improvement for patients with DME as compared with MLP alone. Further confirmation with rigorously well-designed multi-center trials is needed. PMID:26949623

  3. The macular mapping test: a reliability study

    PubMed Central

    Bartlett, Hannah; Davies, Leon N; Eperjesi, Frank

    2005-01-01

    Background Age-related macular degeneration (ARMD) is the leading cause of visual disability in people over 60 years of age in the developed world. The success of treatment deteriorates with increased latency of diagnosis. The purpose of this study was to determine the reliability of the macular mapping test (MMT), and to investigate its potential as a screening tool. Methods The study population comprised of 31 healthy eyes of 31 participants. To assess reliability, four macular mapping test (MMT) measurements were taken in two sessions separated by one hour by two practitioners, with reversal of order in the second session. MMT readings were also taken from 17 age-related maculopathy (ARM), and 12 AMD affected eyes. Results For the normal cohort, average MMT scores ranged from 85.5 to 100.0 MMT points. Scores ranged from 79.0 to 99.0 for the ARM group and from 9.0 to 92.0 for the AMD group. MMT scores were reliable to within ± 7.0 points. The difference between AMD affected eyes and controls (z = 3.761, p = < 0.001) was significant. The difference between ARM affected eyes and controls was not significant (z = -0.216, p = 0.829). Conclusion The reliability data shows that a change of 14 points or more is required to indicate a clinically significant change. This value is required for use of the MMT as an outcome measure in clinical trials. Although there was no difference between MMT scores from ARM affected eyes and controls, the MMT has the advantage over the Amsler grid in that it uses a letter target, has a peripheral fixation aid, and it provides a numerical score. This score could be beneficial in office and home monitoring of AMD progression, as well as an outcome measure in clinical research. PMID:16092954

  4. Electrophysiological assessment of aphakic cystoid macular oedema.

    PubMed Central

    Salzman, J; Seiple, W; Carr, R; Yannuzzi, L

    1986-01-01

    Focal electroretinograms (FERG), pattern electroretinograms (PERG), and visual evoked potentials (VEP) were studied in a group of 30 aphakic patients with cystoid macular oedema (ACME). When compared with a control group of age-matched aphakics, 35% of patients were found to have abnormal FERG responses and 53%--over half of whom had normal FERG responses--showed abnormal PERG amplitudes. Although most of the patients had associated optic disc leakage, VEP latencies were normal in 26 out of 30. These results may explain the more severe visual loss seen in some ACME patients where the ophthalmologically visible retinal changes do not seem sufficient to explain such reduction in vision. PMID:3790483

  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. Role of Unfolded Protein Response Dysregulation in Oxidative Injury of Retinal Pigment Epithelial Cells

    PubMed Central

    Chen, Chen; Cano, Marisol; Wang, Joshua J.; Li, Jingming; Huang, Chuangxin; Yu, Qiang; Herbert, Terence P.; Handa, James T.

    2014-01-01

    Abstract Aims: Age-related macular degeneration (AMD), a major cause of legal blindness in the elderly, is associated with genetic and environmental risk factors, such as cigarette smoking. Recent evidence shows that cigarette smoke (CS) that contains high levels of potent oxidants preferably targets retinal pigment epithelium (RPE) leading to oxidative damage and apoptosis; however, the mechanisms are poorly understood. The present study aimed to investigate the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in CS-related RPE apoptosis. Results: ER stress and proapoptotic gene C/EBP homologous protein (CHOP) were induced in the RPE/choroid complex from mice exposed to CS for 2 weeks and in human RPE cells treated with hydroquinone, a potent oxidant found at high concentrations in CS. Suppressing ER stress or inhibiting CHOP activation by pharmacological chaperones or genetic approaches attenuated hydroquinone-induced RPE cell apoptosis. In contrast to enhanced CHOP activation, protein level of active X-box binding protein 1 (XBP1), a major regulator of the adaptive UPR, was reduced in hydroquinone-treated cells. Conditional knockout of XBP1 gene in the RPE resulted in caspase-12 activation, increased CHOP expression, and decreased antiapoptotic gene Bcl-2. Furthermore, XBP1-deficient RPE cells are more sensitive to oxidative damage induced by hydroquinone or NaIO3, a CS-unrelated chemical oxidant. Conversely, overexpressing XBP1 protected RPE cells and attenuated oxidative stress-induced RPE apoptosis. Innovation and Conclusion: These findings provide strong evidence suggesting an important role of ER stress and the UPR in CS-related oxidative injury of RPE cells. Thus, the modulation of the UPR signaling may provide a promising target for the treatment of AMD. Antioxid. Redox Signal. 20, 20912106. PMID:24053669

  7. Proliferative diabetic retinopathy is associated with a low level of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor. a pilot study.

    PubMed

    Boehm, B O; Lang, G; Feldmann, B; Kurkhaus, A; Rosinger, S; Volpert, O; Lang, G K; Bouck, N

    2003-06-01

    Retinopathy is the most common microvascular diabetes complication and represents a major threat to the eyesight. The aim of this study was to address the role of pro- and anti-angiogenic molecules in diabetic retinopathy in the aqueous humor of the eye. Aqueous humor was collected at cataract surgery from 19 diabetic patients and from 13 age- and sex-matched normoglycemic controls. Levels of pro-angiogenic vascular endothelial growth factor (VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) were determined. Angiogenic activity of the aqueous humor was quantified by measuring its effect on the migration of capillary endothelial cells. In the aqueous fluid, VEGF levels were increased in diabetics (mean values: 501 vs. 367 pg/ml; p = 0.05), compared to controls. PEDF was found to be decreased in diabetics (mean values: 2080 vs. 5780 ng/ml; p = 0.04) compared to controls. In seven diabetic patients with proliferative retinopathy, the most profound finding was a significant decrease of the PEDF level (mean value: 237 ng/ml), whereas VEGF levels were comparable to diabetic patients without proliferation (mean value: 3153; p = 0.003). Angiogenic activity in samples of patients from the control group was generally inhibitory due to PEDF, and inhibition was blocked by neutralizing antibodies to PEDF. Likewise, in diabetics without proliferation, angiogenic activity was also blocked by antibodies to PEDF. We will demonstrate here that the level of the natural ocular anti-angiogenic agent PEDF is inversely associated with proliferative retinopathy. PEDF is an important negative regulator of angiogenic activity of aqueous humor. Our data may have implications for the development of novel regimens for diabetic retinopathy. PMID:12920663

  8. 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. PMID:25941875

  9. 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.

  10. 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

  11. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema.

    TOXLINE Toxicology Bibliographic Information

    Diabetic Retinopathy Clinical Research Network; Wells JA; Glassman AR; Ayala AR; Jampol LM; Aiello LP; Antoszyk AN; Arnold-Bush B; Baker CW; Bressler NM; Browning DJ; Elman MJ; Ferris FL; Friedman SM; Melia M; Pieramici DJ; Sun JK; Beck RW

    2015-03-26

    BACKGROUND: The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown.METHODS: At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year.RESULTS: From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56).CONCLUSIONS: Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, http://clinicaltrials.gov/ct2/show/NCT01627249 target=new>NCT01627249.).

  12. 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.

  13. 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

  14. Macular abnormalities in Italian patients with retinitis pigmentosa

    PubMed Central

    Testa, Francesco; Rossi, Settimio; Colucci, Raffaella; Gallo, Beatrice; Di Iorio, Valentina; della Corte, Michele; Azzolini, Claudio; Melillo, Paolo; Simonelli, Francesca

    2014-01-01

    Aim To investigate the prevalence of macular abnormalities in a large Caucasian cohort of patients affected by retinitis pigmentosa (RP). Methods A retrospective study was performed by reviewing the medical records and optical coherence tomography (OCT) scans in a cohort of 581 RP patients in order to assess the presence of macular abnormalities —that is, cystoid macular oedema (CMO), epiretinal membrane (ERM), vitreo-macular traction syndrome, and macular hole. Results Macular abnormalities were observed in 524 (45.1%) out of the 1161 examined eyes. The most frequent abnormality was CMO, observed in 237 eyes (20.4%) from 133 patients (22.9%), followed by ERM, assessed in 181 eyes (15.6%) from 115 patients (19.8%). Moreover, vitreo-retinal abnormalities were significantly (p<0.05) associated with older age, cataract surgery, or cataract. CMO appeared to be significantly (p<0.05) associated with female gender, autosomic dominant inheritance pattern, and cataract. Conclusions Macular abnormalities are more frequent in RP compared to the general population. For that reason, screening RP patients with OCT is highly recommended to follow-up the patients, evaluate the natural history of disease, and identify those patients who could benefit from current or innovative therapeutic strategies. PMID:24532797

  15. Idiopathic macular telangiectasia type 2: 
the progressive vasculopathy.

    PubMed

    Engelbert, Michael; Yannuzzi, Lawrence A

    2012-11-01

    Purpose. To describe the complete sequence of the progressive vasculopathy in macular telangiectasia type 2.
Methods. This is a report of a case demonstrating the complete vasogenic sequence in macular telangiectasia type 2 over the course of 15 years, and representative images from a collective of 150 patients with macular telangiectasia type 2 employing fundus photography, fluorescein angiography, and optical coherence tomography.
Results. Macular telangiectasia may progress along a predictable vasogenic sequence which consists of nonproliferative stages, characterized by temporal loss of macular luteopigment and inner retinal volume loss in the absence of vascular changes, followed by a progressive proliferative vasculopathy, first involving the deep capillary plexus with eventual extension of the vascular changes circumferentially in the inner retinal capillary plexus. Late proliferative stages may become indistinguishable from advanced neovascular age-related macular degeneration.
Conclusions. While it is rare to observe the complete vasogenic sequence of macular telangiectasia type 2, a classification into nonproliferative and proliferative stages can be established, and may prove helpful as the mechanisms driving the pathogenic process through those stages are identified. PMID:23138663

  16. 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

  17. Effect of amaranthus pigments on quality characteristics of pork sausages.

    PubMed

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

    2012-10-01

    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

  18. A multimodal approach to diabetic macular edema.

    PubMed

    Au, Adrian; Singh, Rishi P

    2016-04-01

    Diabetic retinopathy is a common complication of uncontrolled diabetes. A complication is diabetic macular edema, which is the leading cause of blindness in patients with diabetic retinopathy. Historically, management of these conditions was laser photocoagulation with regulation of blood pressure, blood sugar, and cholesterol. The initial studies demonstrated that this treatment regimen prevented further visual deterioration but did not improve visual acuity. Novel studies identifying the presence of vascular endothelial growth factor (VEGF) in the eye with accompanying elucidation of diabetic pathophysiology allowed for the development of alternative therapies, namely antibodies against VEGF and corticosteroids. These two therapies revolutionized the management of diabetic macular edema by not only preventing vision loss, but also improving overall vision. In this review, we outline the major breakthroughs and underlying thought processes of the paradigm shifts that have occurred in management of these conditions. Further, we present how the evolving role of anti-inflammatory and anti-VEGF therapies, in a combinatorial approach, may provide further permutations to optimize treatment. PMID:26853628

  19. 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

  20. 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. PMID:25808681

  1. The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa Patients with or without Cystoid Macular Edema

    PubMed Central

    Sandberg, Michael A.; Pearce, Elizabeth N.; Harper, Shyana; Weigel-DiFranco, Carol; Hart, Lois; Rosner, Bernard; Berson, Eliot L.

    2014-01-01

    Importance Current treatments for cystoid macular edema in retinitis pigmentosa are not always effective, may lead to adverse side effects, and may not restore loss of visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce cystoid macular edema in retinitis pigmentosa. Objective To determine whether central foveal thickness in the presence of cystoid macular edema is related to dietary iodine intake inferred from urinary iodine concentration in non-smoking adults with retinitis pigmentosa. Design Cross-sectional study. Setting Institutional referral center. Participants Non-smoking adult patients with retinitis pigmentosa (n = 212, ages 18 to 69 years) with a visual acuity ? 20/200 in at least one eye. Main outcome measure The relationship of log central foveal thickness measured by optical coherence tomography to urinary iodine concentration measured from multiple spot samples and represented as a 3-level classification variable (< 100 ?g/L, 100 ?g/L - 199 ?g/L, and ? 200 ?g/L), assigning greater weight to patients with more reliable urinary iodine concentration estimates. Results Analyses were limited to 199 patients after excluding 11 patients who failed to return urine samples for measuring urinary iodine concentration and 2 outliers for urinary iodine concentration. Thirty-six percent of these patients had cystoid macular edema in one or both eyes. Although log central foveal thickness was inversely related to urinary iodine concentration based on all patients (p = 0.02), regression of log central foveal thickness on urinary iodine concentration separately for patients with and without cystoid macular edema showed a strong inverse significant relationship for the former group (p < 0.001) and no significant relationship for the latter group as tested (p = 0.66). In contrast, we found no significant association between cystoid macular edema prevalence and urinary iodine concentration based on the entire sample as tested. Conclusions and Relevance A higher urinary iodine concentration in non-smoking adults with retinitis pigmentosa was significantly associated with less central foveal swelling in eyes with cystoid macular edema. Additional study is required to determine whether an iodine supplement can limit or reduce the extent of cystoid macular edema in patients with retinitis pigmentosa. PMID:24993773

  2. 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 iconographer uses earthly creations to create divine images: "Thine own of Thine own we offer unto Thee." (Byzantine Liturgy). Thus, by combining geology with art and religion, I can render homage to God through His creation by using minerals of the Planet Earth, as natural pigments in painting His image.

  3. Bilateral macular injury from a green laser pointer

    PubMed Central

    Dirani, Ali; Chelala, Elias; Fadlallah, Ali; Antonios, Rafic; Cherfan, George

    2013-01-01

    We report the case of a 13-year-old boy who had a bilateral macular injury after playing with a green laser pointer for a duration of 1 minute. Clinical examination revealed a decrease in visual acuity and macular injury in both eyes, and imaging investigations revealed a bilateral macular lesion due to exposure to the laser pointer. At 3 months’ follow up, visual function had improved but remained partially impaired. This case emphasizes the importance of cautious and appropriate use of laser pointer devices because of the potential vision-threatening hazards induced by mishandling of these devices. PMID:24204114

  4. Matrix Metalloproteinase Activity Creates Pro-Angiogenic Environment in Primary Human Retinal Pigment Epithelial Cells Exposed to Complement

    PubMed Central

    Bandyopadhyay, Mausumi; Rohrer, Bärbel

    2012-01-01

    Purpose. Mechanistic studies have shown that inflammation, complement activation, extracellular matrix (ECM) turnover, growth factor imbalance, and oxidative stress are fundamental components of age-related macular degeneration (AMD). Matrix metalloproteinases (MMPs) mediate ECM turnover but also process various bioactive molecules. Here, we tested whether complement attack on RPE monolayers changes MMP secretion and activation, thereby altering the availability of growth factors in the extracellular space. Methods. Human embryonic RPE monolayers with stable transepithelial resistance (TER) were established. Complement activation was induced with H2O2 and normal human serum. MMP-2/9, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) protein, and mRNA levels were analyzed by Western blotting, ELISA, and real-time PCR; activity of MMP-2/9 by gelatin zymography. Results. Complement activation resulted in a loss of TER, which required transient membrane attack complex formation, activation of the alternative pathway, and VEGF secretion and signaling. Despite the generation of reactive oxygen species, cellular integrity or intracellular adenosine triphosphate (ATP) levels were unaffected. However, expression of MMP-2/9 and their protease activity was elevated. Inhibition of MMP-2/9 activity increased PEDF and decreased VEGF levels in the apical and basal supernatants but had no effect on their expression levels. VEGF levels in the supernatant correlated with the level TER reduction. Conclusions. These studies suggest that complement activation, by altering the expression and activation of MMPs, has the ability to generate a proangiogenic environment by altering the balance between VEGF and PEDF. Our findings link reported results that have been associated with AMD pathogenesis; oxidative stress; complement activation; VEGF/PEDF ratio; and MMP activity. PMID:22408008

  5. SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress.

    PubMed

    Li, Langen; Wei, Wei; Zhang, Yufeng; Tu, Gerile; Zhang, Yanmei; Yang, Jia; Xing, Yiqiao

    2015-08-01

    It has been previously demonstrated that there are interactions between sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3), which have versatile roles in various microenvironments. However, whether or not there is crosstalk between these two molecules during oxidative stress, and what mechanism of crosstalk occurs in retinal pigmented epithelium cells (RPEs), the protection of which may delay the process of age-related macular degeneration (AMD), has required further elucidation. The present study aimed to investigate the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative stress. The rates of proliferation and apoptosis, levels of intracellular reactive oxygen species and cell senescence of RPEs, induced by oxidants [H2O2 and oxidized low density lipoprotein (oxLDL)], were evaluated. The results revealed a downregulation of SirT1 expression, and an upregulation of STAT3 expression during oxidative stress. Further investigation indicated that SirT1 protected RPEs from oxidative stress-induced damage. Furthermore, gain- and loss-of-function experiments indicated that SirT1 had negative effects on the regulation of STAT3 expression in RPEs during oxidative stress. Notably, STAT3 directly protected the cells from oxidative stress, rather than depending on SirT1. Additionally, the protective effects of STAT3 had no association with the modulation of cell senescence during oxidative stress. In conclusion, SirT1 had negative effects on the regulation of STAT3 expression during oxidative stress. However, SirT1 and STAT3 demonstrated protective roles against oxidative stress in RPEs. These results therefore suggested that there was an equilibrium mechanism between SirT1 and STAT3 against oxidative stress, meaning that an equilibrium mechanism is required to be considered when combined application of STAT3 and SirT1 were performed to treat AMD. PMID:25847123

  6. 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 mechanisms involved in the modification of functions of the RPE during macular edema. PMID:26912969

  7. The risk of fellow eye visual loss with unilateral retinal pigment epithelial tears.

    PubMed

    Schoeppner, G; Chuang, E L; Bird, A C

    1989-12-15

    To identify the magnitude of risk of fellow-eye visual loss, we reviewed the records of 43 patients with unilateral central visual loss caused by a tear of detached retinal pigment epithelium seen in our institution over a period of one to 13 years. Loss of vision because of complications of age-related macular disease occurred in 16 of 43 patients (37%) in the first year, seven of 23 patients (30%) in the second year, and eight of 16 patients (50%) in the third year. An additional five patients lost visual acuity between the third and eighth years of follow-up. The cumulative risk of loss of visual acuity was 37% in one year, 59% in two years, and 80% in three years. Visual loss occurred in 29 of the 36 eyes as a result of a complication of retinal pigment epithelial detachment. The magnitude of risk to the fellow eye was greater than has been documented in unselected age-related macular degeneration. PMID:2596548

  8. Novel Compstatin Family Peptides Inhibit Complement Activation by Drusen-Like Deposits in Human Retinal Pigmented Epithelial Cell Cultures

    PubMed Central

    Gorham, Ronald D.; Forest, David L.; Tamamis, Phanourios; de Victoria, Aliana López; Kraszni, Márta; Kieslich, Chris A.; Banna, Christopher D.; Bellows-Peterson, Meghan L.; Larive, Cynthia K.; Floudas, Christodoulos A.; Archontis, Georgios; Johnson, Lincoln V.; Morikis, Dimitrios

    2013-01-01

    We have used a novel human retinal pigmented epithelial (RPE) cell-based model that mimics drusen biogenesis and the pathobiology of age-related macular degeneration to evaluate the efficacy of newly designed peptide inhibitors of the complement system. The peptides belong to the compstatin family and, compared to existing compstatin analogs, have been optimized to promote binding to their target, complement protein C3, and to enhance solubility by improving their polarity/hydrophobicity ratios. Based on analysis of molecular dynamics simulation data of peptide-C3 complexes, novel binding features were designed by introducing intermolecular salt bridge-forming arginines at the N-terminus and at position -1 of N-terminal dipeptide extensions. Our study demonstrates that the RPE cell assay has discriminatory capability for measuring the efficacy and potency of inhibitory peptides in a macular disease environment. PMID:23954241

  9. Management of oral melanin pigmentation.

    PubMed

    Karydis, Anastasios; Bland, Paul; Shiloah, Jacob

    2012-01-01

    Melanin is an endogenous pigment responsible for human tissue coloration of the skin, mucosa, hair, eyes and parts of the brain. In the skin, its function is protection from the harmful effects of UV radiation. Its purpose in oral tissues has not yet been determined. Oral pigmentation could be an esthetic issue for some patients, particularly when it is located on the anterior labial gingiva in individuals with a high smile line. This article presents and describes several different approaches for the management of oral melanin pigmentation. PMID:23420974

  10. Macular Oedema Related to Idiopathic Macular Telangiectasia Type 1 Treated with Dexamethasone Intravitreal Implant (Ozurdex)

    PubMed Central

    Kamal, Ahmed

    2014-01-01

    A 65-year-old female presented with visual disturbance in her right eye lasting for over 2 months. Following investigations, she was diagnosed with MacTel type 1 in the right eye. Visual symptoms were refractory to initial treatment with intravitreal bevacizumab and thereafter intravtireal triamicinolone. The patient was then treated with Ozurdex, following which central macular thickness (CMT) decreased (from 397 μm to 286 μm) and visual acuity deteriorated (from logMAR 0.48 to 0.59). At 14 weeks posttreatment with Ozurdex, a recurrence of cystoid macular oedema (CMO) was observed. Following a second Ozurdex, visual acuity improved (from logMAR 0.7 to 0.64) and CMT decreased (from 349 μm to 279 μm). An additional recurrence of CMO was observed at eighteen weeks following the second Ozurdex. Following a third Ozurdex injection visual acuity deteriorated (from logMAR 0.74 to 0.78) and CMT decreased (from 332 μm to 279 μm). Conclusion. Treatment of macular oedema secondary to MacTel with Ozurdex demonstrated promising anatomical outcomes. However, visual outcomes continued to gradually deteriorate. PMID:25045562

  11. 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

  12. 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

  13. Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure

    PubMed Central

    Boyer, Nicholas P.; Higbee, Daniel; Currin, Mark B.; Blakeley, Lorie R.; Chen, Chunhe; Ablonczy, Zsolt; Crouch, Rosalie K.; Koutalos, Yiannis

    2012-01-01

    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. PMID:22570475

  14. 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. PMID:25304238

  15. Pharmacological approach to diabetic macular edema.

    PubMed

    Bandello, F; Casalino, G; Loewenstein, A; Goldstein, M; Pelayes, D; Battaglia Parodi, M

    2014-01-01

    Diabetic macular edema (DME) is a highly prevalent cause of vision loss and has a remarkable impact on public health, and on the quality of life of diabetic patients. Even though laser photocoagulation has been the standard of care for decades, a substantial group of patients are unresponsive and fail to improve after laser treatment. Recently, new pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have revolutionized the treatment of DME. The use of intravitreal drugs is supported by the improvement in visual acuity reported by several clinical trials and can limit the potentially destructive effects of the laser treatment. Encouraging results also emerged from studies evaluating the use of a combination therapy, or the association of intravitreal drugs and laser treatment. This review aims at providing a brief synopsis of the main investigations regarding the current pharmacological approach to DME. PMID:24356667

  16. Optical coherence tomography imaging of macular oedema

    PubMed Central

    Trichonas, George; Kaiser, Peter K

    2014-01-01

    Macular oedema (ME) occurs in a wide variety of pathological conditions and accounts for different degrees of vision loss. Early detection of ME is therefore critical for diagnosis and therapeutic management. Optical coherence tomography (OCT) is a non-contact, diagnostic method that uses infrared light, which allows the analysis of the retinal structure by means of high-resolution tomographic cross sections. The identification, localisation, quantification and long-term follow-up of fluid collections are the most important capabilities of OCT. Since the introduction of OCT in clinical practice, it has become an invaluable diagnostic tool and different patterns of ME have been reported. The purpose of this manuscript is to review OCT profiles of ME according to the aetiology and describe what has been reported regarding intraretinal features in vivo. PMID:24934220

  17. Analysis of Indian pigment gallstones

    NASA Astrophysics Data System (ADS)

    Rautray, T. R.; Vijayan, V.; Panigrahi, S.

    2007-02-01

    Particle induced X-ray emission and particle induced γ-ray emission spectroscopic techniques have been carried out to analyse the elemental concentrations of human pigment gallstone samples from eastern region (Orissa) and southern region (Chennai) of India. It was observed that 18 minor/trace elements namely Na, Mg, Al, P, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Br and Pb were present in the pigment gallstone samples of both the regions. Our study reveals that average concentration of all elements except Ni in south Indian pigment gallstone samples is higher than that of corresponding values in east Indian pigment gallstone samples whereas elements like Al, P, S, Cl and V did not show much variation between these two regions. Fourier transform infra-red analysis was carried out to identify the functional groups and the classification of the pigment type gallstones of both the regions. The thermal behaviour of pigment gallstones was carried out by thermogravimetry-derivative thermogravimetry analysis.

  18. p62/sequestosome 1 as a regulator of proteasome inhibitor-induced autophagy in human retinal pigment epithelial cells

    PubMed Central

    Viiri, Johanna; Hyttinen, Juha M. T.; Ryhänen, Tuomas; Rilla, Kirsi; Paimela, Tuomas; Kuusisto, Erkki; Siitonen, Ari; Urtti, Arto; Salminen, Antero

    2010-01-01

    Purpose The pathogenesis of age-related macular degeneration involves impaired protein degradation in retinal pigment epithelial (RPE) cells. The ubiquitin-proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems in eukaryotic cells. Prior to proteolysis, heat shock proteins (HSPs) attempt to refold stress-induced misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. Recently, p62/sequestosome 1 (p62) has been shown to be a key player linking the proteasomal and lysosomal clearance systems. In the present study, the functional roles of p62 and HSP70 were evaluated in conjunction with proteasome inhibitor–induced autophagy in human RPE cells (ARPE-19). Methods The p62, HSP70, and ubiquitin protein levels and localization were analyzed by western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. The p62 and HSP70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. Results Proteasome inhibition evoked the accumulation of perinuclear aggregates that strongly colocalized with p62 and HSP70. The p62 perinuclear accumulation was time- and concentration-dependent after MG-132 proteasome inhibitor loading. The silencing of p62, rather than Hsp70, evoked suppression of autophagy, when related to decreased LC3-II levels after bafilomycin treatment. In addition, the p62 silencing decreased the ubiquitination level of the perinuclear aggregates. Recently, we showed that hsp70 mRNA depletion increased cell death in ARPE-19 cells. Here, we demonstrate that p62 mRNA silencing has similar effects on cellular viability. Conclusions Our findings open new avenues for understanding the mechanisms of proteolytic processes in retinal cells, and could be useful in the development of novel therapies targeting p62 and HSP70. PMID:20680098

  19. TLR4 inhibitor attenuates amyloid-β-induced angiogenic and inflammatory factors in ARPE-19 cells: Implications for age-related macular degeneration.

    PubMed

    Chen, Li; Bai, Yujing; Zhao, Min; Jiang, Yanrong

    2016-04-01

    Subretinally-deposited amyloid-β (Aβ) is an important factor in age‑related macular degradation (AMD) often leading to irreversible blindness in the elderly population. The molecular mechanism underlying Aβ deposition during AMD remains unclear. The expression of inflammatory and angiogenic factors was examined by treatment of retinal pigment epithelial (RPE) cells with the oligomeric form of Aβ (OAβ1-42). Changes in the mRNA expression levels of various cytokines was detected by the QuantiGenePlex 6.0 Reagent system, and the protein expression level was determined by western blotting. Culture supernatants were detected using a multiplex cytokine assay and enzyme-linked immunosorbent assays. The in vitro tube formation was evaluated by a Matrigel assay. The present study highlights that OAβ1‑42 activates the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 and phosphorylation nuclear factor-κB signaling pathway in RPE cells. Additionally, it increased the mRNA and protein expression of interleukin (IL)-6, IL-8, IL-33, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiopoietin 2. Furthermore, the TLR4 inhibitor (COBRA) attenuated the expression of inflammatory and angiogenesis factors, particularly IL-6, IL-8, IL-33, bFGF and VEGF. When human umbilical vein endothelial cells (HUVECs) were co-cultured with the COBRA-treated RPE cell culture supernatant the length of the endothelial cell network (measured by calculating tip cell lengths of endothelial cells) was impaired when compared with the HUVECs that were co‑cultured with the cell supernatant exposed to OAβ1‑42. These results suggest that the TLR4-associated pathway may be a potential target for the treatment of AMD. PMID:26936827

  20. Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents

    PubMed Central

    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

  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. Automatic Detection of Diabetic Retinopathy and Age-Related Macular Degeneration in Digital Fundus Images

    PubMed Central

    Barriga, E. Simon; Murray, Victor; Nemeth, Sheila; Crammer, Robert; Bauman, Wendall; Zamora, Gilberto; Pattichis, Marios S.; Soliz, Peter

    2011-01-01

    Purpose. To describe and evaluate the performance of an algorithm that automatically classifies images with pathologic features commonly found in diabetic retinopathy (DR) and age-related macular degeneration (AMD). Methods. Retinal digital photographs (N = 2247) of three fields of view (FOV) were obtained of the eyes of 822 patients at two centers: The Retina Institute of South Texas (RIST, San Antonio, TX) and The University of Texas Health Science Center San Antonio (UTHSCSA). Ground truth was provided for the presence of pathologic conditions, including microaneurysms, hemorrhages, exudates, neovascularization in the optic disc and elsewhere, drusen, abnormal pigmentation, and geographic atrophy. The algorithm was used to report on the presence or absence of disease. A detection threshold was applied to obtain different values of sensitivity and specificity with respect to ground truth and to construct a receiver operating characteristic (ROC) curve. Results. The system achieved an average area under the ROC curve (AUC) of 0.89 for detection of DR and of 0.92 for detection of sight-threatening DR (STDR). With a fixed specificity of 0.50, the system's sensitivity ranged from 0.92 for all DR cases to 1.00 for clinically significant macular edema (CSME). Conclusions. A computer-aided algorithm was trained to detect different types of pathologic retinal conditions. The cases of hard exudates within 1 disc diameter (DD) of the fovea (surrogate for CSME) were detected with very high accuracy (sensitivity = 1, specificity = 0.50), whereas mild nonproliferative DR was the most challenging condition (sensitivity= 0.92, specificity = 0.50). The algorithm was also tested on images with signs of AMD, achieving a performance of AUC of 0.84 (sensitivity = 0.94, specificity = 0.50). PMID:21666234

  3. Early initial clinical experience with intravitreal aflibercept for wet age-related macular degeneration

    PubMed Central

    Ferrone, Philip J; Anwar, Farihah; Naysan, Jonathan; Chaudhary, Khurram; Fastenberg, David; Graham, Kenneth; Deramo, Vincent

    2014-01-01

    Background Age-related macular degeneration (AMD) is a degenerative process that leads to severe vision loss. Wet AMD is defined by choroidal neovascularisation, leading to the accumulation of subretinal fluid (SRF), macular oedema (ME), and pigment epithelium detachments (PED). Purpose To evaluate the initial clinical experience of conversion from bevacizumab or ranibizumab to aflibercept in wet AMD patients. Methods Records of 250 consecutive wet AMD patients were retrospectively reviewed. Of 250 patients, 29 were naive (with no previous treatment), and 221 were previously treated with bevacizumab (1/3) or ranibizumab (2/3). On average, converted patients received 14 injections every 6 weeks on a treat-and-extend regimen with Avastin or Lucentis before being converted to aflibercept every 7 weeks on average (no loading dose) for three doses. For the purposes of this study, we concentrated on the patients converted to aflibercept since the number of naive patients was too small to draw any conclusion from. Snellen (as logMar) visual acuities, and optical coherence tomography (OCT) were compared predrug and postdrug conversion. Results Converted patients did not show a significant difference in visual acuity or average OCT thickness from preconversion values; however, small improvements in ME (p=0.0001), SRF (p=0.0001), and PED (p=0.008) grading were noted on average after conversion to aflibercept. Conclusions No significant difference in visual outcome or average OCT thickness was observed when switched from bevacizumab or ranibizumab q6 week to aflibercept 7-week dosing, on average. Mild anatomic improvements did occur in converted patients with regard to ME, SRF and PED improvement, on average, after conversion to aflibercept, and aflibercept was injected less frequently. No serious adverse reactions, including ocular infections or inflammation, as well as ocular and systemic effects were noted. PMID:24795335

  4. 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 require further examination. PMID:25127409

  5. Cone photoreceptor oil droplet pigmentation is affected by ambient light intensity.

    PubMed

    Hart, Nathan S; Lisney, Thomas J; Collin, Shaun P

    2006-12-01

    The cone photoreceptors of many vertebrates contain spherical organelles called oil droplets. In birds, turtles, lizards and some lungfish the oil droplets are heavily pigmented and function to filter the spectrum of light incident upon the visual pigment within the outer segment. Pigmented oil droplets are beneficial for colour discrimination in bright light, but at lower light levels the reduction in sensitivity caused by the pigmentation increasingly outweighs the benefits generated by spectral tuning. Consequently, it is expected that species with pigmented oil droplets should modulate the density of pigment in response to ambient light intensity and thereby regulate the amount of light transmitted to the outer segment. In this study, microspectrophotometry was used to measure the absorption spectra of cone oil droplets in chickens (Gallus gallus domesticus) reared under bright (unfiltered) or dim (filtered) sunlight. Oil droplet pigmentation was found to be dependent on the intensity of the ambient light and the duration of exposure to the different lighting treatments. In adult chickens reared in bright light, the oil droplets of all cone types (except the violet-sensitive single cones, whose oil droplet is always non-pigmented) were more densely pigmented than those in chickens reared in dim light. Calculations show that the reduced levels of oil droplet pigmentation in chickens reared in dim light would increase the sensitivity and spectral bandwidth of the outer segment significantly. The density of pigmentation in the oil droplets presumably represents a trade-off between the need for good colour discrimination and absolute sensitivity. This might also explain why nocturnal animals, or those that underwent a nocturnal phase during their evolution, have evolved oil droplets with low pigment densities or no pigmentation or have lost their oil droplets altogether. PMID:17114410

  6. [Metabolic therapy for early treatment of age-related macular degeneration].

    PubMed

    Fehér, János; Kovács, Bálint; Kovács, Illés; Schvöller, Mónika; Corrado Balacco, Gabrieli

    2007-12-01

    Currently, age-related macular degeneration is one of the most common eye diseases causing severe and permanent loss of vision. This disease is estimated to affect approximately 300-500 thousand Hungarians. While earlier no treatment was available, in the recent decade an antioxidant therapy became very popular using combinations of high dosage antioxidant vitamins C, E, beta carotene and zinc. Based on theoretical concepts and mostly in vitro experiences, this combination was thought to be effective through neutralizing reactive oxygen species. According to a large clinical trial (AREDS) it reduced progression of intermediate state disease to advanced state, but did not influence early disease. This original combination, due to potential severe side effects, is not on the market anymore. However, the efficacy of modified formulas has not been proved yet. Recently, the metabolic therapy, a combination of omega-3 fatty acids, coenzyme Q10 and acetyl-L-carnitine has been introduced for treating early age-related macular degeneration through improving mitochondrial dysfunction, specifically improving lipid metabolism and ATP production in the retinal pigment epithelium, improving photoreceptor turnover and reducing generation of reactive oxygen species. According to a pilot study and a randomized, placebo-controlled, double blind clinical trial, both central visual field and visual acuity slightly improved after 3-6 months of treatment and they remained unchanged by the end of the study. The difference was statistically significant as compared to the base line or to controls. These functional changes were accompanied by an improvement in fundus alterations: drusen covered area decreased significantly as compared to the base line or to control. Characteristically, all these changes were more marked in less affected eyes. A prospective case study on long-term treatment confirmed these observations. With an exception that after slight improvement, visual functions remained stable, drusen regression continued for years. Sometimes significant regression of drusen was found even in intermediate and advanced cases. All these findings strongly suggested that the metabolic therapy may be the first choice for treating age-related macular degeneration. Currently, this is the only combination of ingredients corresponding to the recommended daily allowance, and at the same time, which showed clinically proved efficacy. PMID:18039616

  7. Laser therapy of pigmented lesions: pro and contra.

    PubMed

    Bukvi? Mokos, Zrinka; Lipozen?i?, Jasna; Ceovi?, Romana; Stulhofer Buzina, Daka; Kostovi?, Kreimir

    2010-01-01

    Although frequently performed, laser removal of pigmented lesions still contains certain controversial issues. Epidermal pigmented lesions include solar lentigines, ephelides, caf 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. PMID:20887701

  8. 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. PMID:26308584

  9. 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 expression. These results are consistent with the notion that choroidal endothelial cell dropout or dedifferentiation occurs early in the pathogenesis of AMD. PMID:24265543

  10. 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.

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

    PubMed Central

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

    2011-01-01

    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. PMID:21198152

  12. Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype.

    PubMed

    Schubert, Timm; Gleiser, Corinna; Heiduschka, Peter; Franz, Christoph; Nagel-Wolfrum, Kerstin; Sahaboglu, Ayse; Weisschuh, Nicole; Eske, Gordon; Rohbock, Karin; Rieger, Norman; Paquet-Durand, François; Wissinger, Bernd; Wolfrum, Uwe; Hirt, Bernhard; Singer, Wibke; Rüttiger, Lukas; Zimmermann, Ulrike; Knipper, Marlies

    2015-10-01

    The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms. PMID:25939269

  13. Treatment of massive subretinal hematoma associated with age-related macular degeneration using vitrectomy with intentional giant tear.

    PubMed

    Isizaki, Eisuke; Morishita, Seita; Sato, Takaki; Fukumoto, Masanori; Suzuki, Hiroyuki; Kida, Teruyo; Ueki, Mari; Ikeda, Tsunehiko

    2016-04-01

    The purpose of this study was to report the surgical outcomes after creating a 120° intentional giant retinal tear for use in removing hemorrhage and subretinal proliferative tissue in patients with polypoidal choroidal vasculopathy (PCV) or age-related macular degeneration (ARMD). This study involved 12 eyes of 12 patients (10 eyes: PCV, 2 eyes: ARMD). After removal of the lens in phakic eyes, we performed a vitrectomy with artificial posterior vitreous detachment. Subsequently, a 120° intentional giant retinal tear was created in the temporal periphery, the retina was then turned, and the subretinal hemorrhage and proliferative tissue were removed. In order to preserve as much of the retinal pigment epithelium (RPE) as possible, we used a bimanual technique under direct visualization. After stretching the retina by use of perfluorocarbon liquid (PFCL), we performed endophotocoagulation around the tear followed by PFCL/silicone oil exchange. Except for 1 eye in which extensive loss of the RPE occurred, the fundus findings and the visual acuity (VA) improved in all patients. In addition, postoperative VA improved to ≥20/50 in 3 eyes in which the macular RPE was preserved. This surgical procedure is an effective treatment for PCV or ARMD patients with extensive subretinal hemorrhage and proliferative tissue. PMID:26216161

  14. Macular edema-like change and pseudopapilledema in a case of Scheie syndrome.

    PubMed

    Usui, T; Shirakashi, M; Takagi, M; Abe, H; Iwata, K

    1991-09-01

    We reported a case of Scheie syndrome in which diffuse fine corneal deposits, pigmentary retinal degeneration, pseudopapilledema, and macular edema-like change were observed bilaterally. This is the first report describing macular change in Scheie syndrome. PMID:1836802

  15. Reduced macular function in ABCA4 carriers

    PubMed Central

    2015-01-01

    Purpose To study retinal function and morphology in ABCA4 carriers to investigate if ABCA4 carriership is associated with any functional or morphological changes and, if so, to explore whether certain mutations may be associated with particularly severe alterations. Methods Eighteen subjects were recruited by means of being the parents of 10 teenagers/young adults with genetically confirmed ABCA4-associated retinal degenerations. The teenagers/young adults are well-known patients and have been followed in our clinic for many years. The eighteen subjects underwent careful ophthalmological examinations, including fundus photography and autofluorescence imaging, Goldmann perimetry, optical coherence tomography (OCT), full-field electroretinography (ffERG), multifocal electroretinography (mERG), and ABCA4 gene sequencing. The ffERG and mERG results were compared with those of healthy controls. Results All subjects carried at least one ABCA4 mutation. Two subjects were compound heterozygous and therefore were excluded from the group-wise statistical analysis. Thirteen different ABCA4 mutations were found. C.2894 A>G (5/18) and c.768 G>T (4/18) were most common. Fourteen of 16 ABCA4 carriers demonstrated significantly altered mERG parameters (reduced amplitudes and/or delayed implicit times (ITs)) compared to normal values. In addition, the two subjects with compound heterozygous ABCA4 mutations had altered mERG parameters. A statistical comparison to the control group showed significantly reduced amplitudes and delayed ITs; p?0.003 for all mERG parameters. FfERG parameters were altered in two ABCA4 carriers and one of the subjects with compound heterozygous ABCA4 mutations (reduced amplitude and delayed IT for the 30 Hz flicker ERG). No significant alterations were found for the whole group of ABCA4 carriers compared to the ffERG control group. Fundus photographs showed subtle to extensive pigmentary changes in several ABCA4 carriers. Conclusions In this study, ABCA4 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.546110T>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

  16. 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

  17. 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

    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

  18. Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells.

    PubMed

    Zhu, Lu; Liu, Zhongbo; Feng, Zhihui; Hao, Jiejie; Shen, Weili; Li, Xuesen; Sun, Lijuan; Sharman, Edward; Wang, Ying; Wertz, Karin; Weber, Peter; Shi, Xianglin; Liu, Jiankang

    2010-11-01

    Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1?) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including ?-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1? led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress. PMID:20149621

  19. Exogenous pigment in Peyer's patches

    SciTech Connect

    Shepherd, N.A.; Crocker, P.R.; Smith, A.P.; Levison, D.A.

    1987-01-01

    Dark brown granular pigment was found consistently in macrophages in the deep aspect of adult Peyer's patches. Tissue sections from intestinal resections of 35 patients with a variety of pathologic diagnoses and of seven postmortem cases with no evidence of gastrointestinal disease were examined for the presence of this pigment. It was found in all patients over the age of 6 years (34 cases) but was not found in any children below that age (eight cases). Scanning electron microscopy with secondary and backscattered electron imaging and x-ray energy spectroscopy were performed on routine histologic sections. The pigmented macrophages contained aluminum and silicon, diffusely present throughout the cytoplasm, and numerous discrete foci of titanium. Pigment containing these same elements has also been found around dilated submucosal lymphatics, in mesenteric lymph nodes, and in some transmural inflammatory aggregates of Crohn's disease. The pigment probably is derived from the diet and actively taken up by Peyer's patches, which are able to incorporate inert particulate matter.

  20. Subretinal AAV2.COMP-Ang1 suppresses choroidal neovascularization and vascular endothelial growth factor in a murine model of age-related macular degeneration.

    PubMed

    Lambert, Nathan G; Zhang, Xiaohui; Rai, Ruju R; Uehara, Hironori; Choi, Susie; Carroll, Lara S; Das, Subrata K; Cahoon, Judd M; Kirk, Brian H; Bentley, Blaine M; Ambati, Balamurali K

    2016-04-01

    To assess whether Tie2-mediated vascular stabilization ameliorates neovascular age-related macular degeneration (AMD), we investigated the impact of adeno-associated virus-mediated gene therapy with cartilage oligomeric matrix protein angiopoietin-1 (AAV2.COMP-Ang1) on choroidal neovascularization (CNV), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF) in a mouse model of the disease. We treated mice with subretinal injections of AAV2.COMP-Ang1 or control (AAV2.AcGFP, AAV2.LacZ, and phosphate-buffered saline). Subretinal AAV2 localization and plasmid protein expression was verified in the retinal pigment epithelium (RPE)/choroid of mice treated with all AAV2 constructs. Laser-assisted simulation of neovascular AMD was performed and followed by quantification of HIF, VEGF, and CNV in each experimental group. We found that AAV2.COMP-Ang1 was associated with a significant reduction in VEGF levels (29-33%, p < 0.01) and CNV volume (60-70%, p < 0.01), without a concomitant decrease in HIF1-α, compared to all controls. We concluded that a) AAV2 is a viable vector for delivering COMP-Ang1 to subretinal tissues, b) subretinal COMP-Ang1 holds promise as a prospective treatment for neovascular AMD, and c) although VEGF suppression in the RPE/choroid may be one mechanism by which AAV2.COMP-Ang1 reduces CNV, this therapeutic effect may be hypoxia-independent. Taken together, these findings suggest that AAV2.COMP-Ang1 has potential to serve as an alternative or complementary option to anti-VEGF agents for the long-term amelioration of neovascular AMD. PMID:26775053

  1. 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

  2. Interocular Symmetry in Macular Choroidal Thickness in Children

    PubMed Central

    Al-Haddad, Christiane; El Chaar, Lama; Noureddin, Baha'

    2014-01-01

    Objective. To report interocular differences in choroidal thickness in children using spectral domain optical coherence tomography (SD-OCT) and correlate findings with biometric data. Methods. This observational cross-sectional study included 91 (182 eyes) healthy children aged 6 to 17 years with no ocular abnormality except refractive error. After a comprehensive eye exam and axial length measurement, high definition macular scans were performed using SD-OCT. Two observers manually measured the choroidal thickness at the foveal center and at 1500 µm nasally, temporally, inferiorly, and superiorly. Interocular differences were computed; correlations with age, gender, refractive error, and axial length were performed. Results. Mean age was 10.40 ± 3.17 years; mean axial length and refractive error values were similar between fellow eyes. There was excellent correlation between the two observers' measurements. No significant interocular differences were observed at any location. There was only a trend for right eyes to have higher values in all thicknesses, except the superior thickness. Most of the choroidal thickness measurements correlated positively with spherical equivalent but not with axial length, age, or gender. Conclusion. Choroidal thickness measurements in children as performed using SD-OCT revealed a high level of interobserver agreement and consistent interocular symmetry. Values correlated positively with spherical equivalent refraction. PMID:25525509

  3. Cadmium exposure and age-related macular degeneration.

    PubMed

    Kim, Myung Hun; Zhao, Di; Cho, Juhee; Guallar, Eliseo

    2016-03-01

    Cadmium (Cd) has been proposed as a risk factor for age-related macular degeneration (AMD), but the association between Cd exposure and AMD risk in large population studies is unknown. This study evaluated the association of Cd exposure with AMD in a large representative sample of Korean men and women. This was a cross-sectional study of 3865 Korean adults ≥40 years of age who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) during 2008-2011. Cd concentrations in whole blood were measured by graphite-furnace atomic absorption spectrometry. The presence of AMD was determined in digital non-mydriatic fundus photographs. Cd levels were higher in participants with AMD compared with those without AMD (1.3 vs 1.1 μg/l, respectively, P<0.001). In fully adjusted models, the odds ratio for AMD comparing the highest with the lowest Cd quartiles was 1.92 (95% CI=1.08-3.39; P for trend 0.029). In restricted cubic spline models, the association between Cd and AMD was approximately linear, with no evidence of threshold effects. Blood Cd concentrations were independently associated with the prevalence of AMD. If the association is proven causal, population-based preventive strategies to decrease Cd exposure could reduce the population burden of AMD. PMID:25388812

  4. 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.

  5. Pigmented Porokeratosis. A Further Variant?

    PubMed

    Tan, Tracy S P; Tallon, Ben

    2016-03-01

    Porokeratosis is a clonal disorder of keratinization characterized by the presence of the cornoid lamella. A number of variants of porokeratosis have been described, based on the clinical features and histologic features of the lesions. The authors present a case of porokeratosis with prominent melanocytic hyperplasia, which was biopsied to clinically exclude melanoma. The authors retrospectively studied cases of porokeratosis to look for the presence of melanocytic hyperplasia. Melanocytic hyperplasia was identified in 8 of 31 cases (25.8%). All of the cases except the index case were clinically nonpigmented but arose in solar damaged skin. This case represents a distinct variant of porokeratosis, and the authors propose the designation pigmented porokeratosis. Melanocytic hyperplasia is a benign condition, and it is important that this is not histologically confused with melanoma in situ, particularly in a context of clinically pigmented lesion. Increased recognition of pigmented porokeratosis is essential to avoid an erroneous diagnosis of melanoma in situ. PMID:26894774

  6. Effect of selective laser trabeculoplasty on macular thickness

    PubMed Central

    Koc, Mustafa; Durukan, Irfan; Koban, Yaran; Ceran, Basak Bastanci; Ayar, Orhan; Ekinci, Metin; Yilmazbas, Pelin

    2015-01-01

    Background To investigate the effects of selective laser trabeculoplasty (SLT) on macular thickness change. Methods Forty eyes of 40 consecutive patients with uncontrolled primary open-angle glaucoma with medical treatment were included in this prospective study. SLT was performed to the inferior 180°, and macular thickness was measured. Data were collected before SLT, and 1 week and 1 month after SLT. Macular thickness evaluation was performed in five quadrants, the central 1 mm quadrant (fovea = F), the nasal 3 mm quadrant surrounding F (NQ), temporal quadrant, superior quadrant (SQ), and inferior quadrant (IQ). The preoperative and postoperative thicknesses were compared. Results There was an increase in macular thickness in the NQ, IQ, and SQ on the first week after SLT compared to preoperative measurements. On the other hand, there was no significant increase in the F and temporal quadrant. On the first month after SLT, thickness in the NQ, IQ, and SQ was back to preoperative measurements, and there was no significant change between the preoperative measurements in any quadrant. Conclusion There was no significant increase in macular thickness shortly after SLT in our study. PMID:26719665

  7. 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.

  8. A protective effect of anthocyanins and xanthophylls on UVB-induced damage in retinal pigment epithelial cells.

    PubMed

    Silván, Jose Manuel; Reguero, Marina; de Pascual-Teresa, Sonia

    2016-02-17

    Increased exposure to solar ultraviolet B (UVB) radiation causes oxidative damage that may promote age related macular degeneration (AMD) and other ocular pathologies. This study is aimed to demonstrate the protective effects of some anthocyanins and xanthophylls against the UVB-induced oxidative damage to retinal pigment epithelial (RPE) cells. ARPE-19 cells were treated with 5 μM cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, lutein, zeaxanthin or a mixture of cyanidin-3-O-glucoside : zeaxanthin prior to UVB exposure (500 J m(-2)). Cell viability and mitogen-activated protein kinase (MAPK) phosphorylation were determined by MTT assay and western blot analysis, respectively. Oxidative damage was evaluated by measuring the intracellular reactive oxygen species (ROS). The data showed that UVB irradiation reduces the cell viability to 46% with increasing of intracellular ROS levels and phosphorylation of MAPKs. However, pre-treatment (60 min) with 5 μM cyanidin-3-O-glucoside, lutein or zeaxanthin significantly reduced cellular ROS levels and phosphorylation of MAPKs (JNK1/2 and p38) mediated by UVB irradiation and subsequently increased cell viability. Thus, results show that UVB irradiation is able to induce apoptosis in ARPE-19 cells through oxidative stress; however anthocyanins and xanthophylls pre-treatment can attenuate this damage. This suggests that cyanidin-3-O-glucoside, lutein and zeaxanthin are effective in preventing UVB-induced damage in RPE cells and may be suitable as chemoprotective factors for the prevention of ocular damage. The use of natural dietary antioxidants might reduce ocular oxidative damage caused by UVB radiation. PMID:26781209

  9. 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.

  10. 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

  11. Animal models of age related macular degeneration.

    PubMed

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    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

  12. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

    Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

    2013-01-01

    Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

  13. 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 determined (0.29 mSv) is comparable to diagnostic procedures involving the head, such as an x-ray or CT scan. Thus, the computational assessment performed indicates that a previously established therapeutic dose can be delivered effectively to the macula with IRay(TM) without the potential for secondary complications.

  14. Relative photoreactivity of pigment inclusions of the retinal pigment epithelium

    NASA Astrophysics Data System (ADS)

    Glickman, Randolph D.; Dontsov, Alexander E.; Ostrovsky, Michail A.

    1998-05-01

    The cellular pigments of the retinal pigment epithelium are photoactive; that is, they promote free radical oxidative reactions when illuminated with visible or ultraviolet light. This activity is sufficient to cause photo-oxidation of several major cellular components such as antioxidants, dinucleotide cofactors, proteins and fatty acids. The present investigation determined the relative ability of melanin, lipofuscin, and melanolipofuscin granules isolated from human and bovine eyes to oxidize linoleic and docosahexaenoic acids, which are polyunsaturated fatty acids. The dark reactivity as well as the light-stimulated reactions were determined. All RPE pigment granules stimulated fatty acid oxidation when irradiated with the blue-green (488.1 and 514.5 nm) emission of the Argon-ion laser. Only lipofuscin, however, caused peroxidation of fatty acids in the dark. These findings not only suggest that accumulation of lipofuscin in the aging eye may contribute to increased photo-oxidative stress to the retina and RPE, but also that the photoactive RPE pigments might serve as endogenous photosensitizers for therapeutic applications.

  15. Expression of pigment epithelium‐derived factor and thrombospondin‐1 regulate proliferation and migration of retinal pigment epithelial cells

    PubMed Central

    Farnoodian, Mitra; Kinter, James B.; Yadranji Aghdam, Saeed; Zaitoun, Ismail; Sorenson, Christine M.; Sheibani, Nader

    2015-01-01

    Abstract Age‐related macular degeneration (AMD) is the leading cause of vision loss among elderly. Although the pathogenesis of AMD is associated with retinal pigmented epithelium (RPE) dysfunction and abnormal neovascularization the detailed mechanisms remain unresolved. RPE is a specialized monolayer of epithelial cells with important functions in ocular homeostasis. Pathological RPE damage contributes to major ocular conditions including retinal degeneration and irreversible loss of vision in AMD. RPE cells also assist in the maintenance of the ocular angiogenic balance by production of positive and negative regulatory factors including vascular endothelial growth factor (VEGF), thrombospondin‐1 (TSP1), and pigment epithelium‐derived factor (PEDF). The altered production of PEDF and TSP1, as endogenous inhibitors of angiogenesis and inflammation, by RPE cells have been linked to pathogenesis of AMD and choroidal and retinal neovascularization. However, lack of simple methods for isolation and culture of mouse RPE cells has resulted in limited knowledge regarding the cell autonomous role of TSP1 and PEDF in RPE cell function. Here, we describe a method for routine isolation and propagation of RPE cells from wild‐type, TSP1, and PEDF‐deficient mice, and have investigated their impact on RPE cell function. We showed that expression of TSP1 and PEDF significantly impacted RPE cell proliferation, migration, adhesion, oxidative state, and phagocytic activity with minimal effect on their basal rate of apoptosis. Together, our results indicated that the expression of PEDF and TSP1 by RPE cells play crucial roles not only in regulation of ocular vascular homeostasis but also have significant impact on their cellular function. PMID:25602019

  16. Spontaneous Closure of a Full-Thickness Macular Hole Associated with Proliferative Diabetic Retinopathy and Persistent Vitreomacular Traction

    PubMed Central

    Reinherz, Benjamin J.; Rubin, Jeffrey S.

    2016-01-01

    Diabetic retinopathy worsens the prognosis of macular holes compared to those of idiopathic etiology. While spontaneous closure of idiopathic macular holes is a well-documented phenomenon, spontaneous closure of macular holes associated with proliferative diabetic retinopathy is rare. We report a case of spontaneous closure of a macular hole associated with proliferative diabetic retinopathy and persistent vitreomacular traction. PMID:27099607

  17. Spontaneous Closure of a Full-Thickness Macular Hole Associated with Proliferative Diabetic Retinopathy and Persistent Vitreomacular Traction.

    PubMed

    Reinherz, Benjamin J; Rubin, Jeffrey S

    2016-01-01

    Diabetic retinopathy worsens the prognosis of macular holes compared to those of idiopathic etiology. While spontaneous closure of idiopathic macular holes is a well-documented phenomenon, spontaneous closure of macular holes associated with proliferative diabetic retinopathy is rare. We report a case of spontaneous closure of a macular hole associated with proliferative diabetic retinopathy and persistent vitreomacular traction. PMID:27099607

  18. Kinetics of Lipofuscin Formation in Aging Retinal Pigment Epithelium Cells

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  19. Effect of curcumin on aging retinal pigment epithelial cells

    PubMed Central

    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. PMID:26445530

  20. Lysosomes: Regulators of autophagy in the retinal pigmented epithelium.

    PubMed

    Sinha, Debasish; Valapala, Mallika; Shang, Peng; Hose, Stacey; Grebe, Rhonda; Lutty, Gerard A; Zigler, J Samuel; Kaarniranta, Kai; Handa, James T

    2016-03-01

    The retinal pigmented epithelium (RPE) is critically important to retinal homeostasis, in part due to its very active processes of phagocytosis and autophagy. Both of these processes depend upon the normal functioning of lysosomes, organelles which must fuse with (auto)phagosomes to deliver the hydrolases that effect degradation of cargo. It has become clear that signaling through mTOR complex 1 (mTORC1), is very important in the regulation of lysosomal function. This signaling pathway is becoming a target for therapeutic intervention in diseases, including age-related macular degeneration (AMD), where lysosomal function is defective. In addition, our laboratory has been studying animal models in which the gene (Cryba1) for βA3/A1-crystallin is deficient. These animals exhibit impaired lysosomal clearance in the RPE and pathological signs that are similar to some of those seen in AMD patients. The data demonstrate that βA3/A1-crystallin localizes to lysosomes in the RPE and that it is a binding partner of V-ATPase, the proton pump that acidifies the lysosomal lumen. This suggests that βA3/A1-crystallin may also be a potential target for therapeutic intervention in AMD. In this review, we focus on effector molecules that impact the lysosomal-autophagic pathway in RPE cells. PMID:26321509

  1. [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 agreement. We also found more cases of PCV among the Japanese than among the French. II. PCV. About 50% of exudative AMD cases in the Japanese population are PCV. Because of its peculiar angiographic findings, PCV has long been considered to be a distinct clinical entity different from the usual exudative AMD. Also, there have been serious discussions on the nature of PCV. In our analyses, about 20% of PCV cases show rather large lesion sizes that exceed the vascular arcade. Scar formation in the macula and compromised vision are frequent findings in such cases. The occurrence of PCV in the inferior staphyloma or in angioid streaks shows heterogeneity in PCV. These findings suggest that PCV may be a finding on indocyanine green angiography rather than a distinct clinical entity. Spectral domain OCT examination shows that the branching vascular network of PCV is located between the retinal pigment epithelium and Bruch's membrane. In cases with retinal pigment epithelial detachment, CNV from the branching vascular network was found to extend along the roof of the detached retinal pigment epithelium. Such findings show that the branching vascular network of PCV is type 1 CNV. Complement factor H (CFH) and age-related maculopathy 2 (ARMS2)/High temperature requirement 1 (HTRA1) located on chromosome 10 (10q26) are well-established disease susceptible genes of AMD. In the Japanese, the prevalence of CFH Y402H gene polymorphism is low and ARMS2/HITRA1 plays a more important role in the development of AMD. In ARMS2 A69S polymorphism, a large deletion/insertion (443de1/54ins) that is reported in Caucasians was also found in Japanese. Thus, the genetic background of Caucasian and Japanese AMD is quite similar, as is also the case with exudative AMD and PCV. Our findings show that PCV is not a distinct clinical entity but is a subtype of exudative AMD. III. Exudative AMD with choroidal vascular hyperpermeability. Choroidal vascular hyperpermeability observed in central serous chorioretinopathy can be found in about 20% to 30% of exudative AMD cases in Japanese. Such cases often show a thick choroid, lack of drusen, and rather good visual prognosis with slow progression of the disease. Recently, "pachychoroid neovasculopathy" has been described by a group from New York. Such cases of AMD with choroidal vascular hyperpermeability, a thick choroid, and lack of drusen appears to belong to pachychoroid neovasculopathy. We studied the risk allele frequencies of CFH I62V and ARMS2 A69S gene polymorphisms in three groups : usual exudative AMD, pachychoroid neovasculopathy, and normal controls. Interestingly, cases of pachychoroid neovasculopathy show different gene polymorphisms of CFH I62V and ARMS2 A69S from the usual cases of exudative AMD and a more similar pattern to normal controls. Therefore, the possible mechanisms of the CNV development in such cases may differ from the classic well-documented drusen-dependent pathways. IV. Atrophic AMD in Japanese. Data from the Nagahama Cohort study show an increasing prevalence of drusen in Japanese. Recently, more extensive information on drusen has become available and the redefinition of drusen is currently in progress. In particular, the importance of reticular pseudodrusen (RPD) is more widely appreciated. This type of drusen is often found in Japanese AMD. Although the nature and location of RPD are still debatable, many investigators believe that this type of drusen is located under the sensory retina rather than under Bruch's membrane. In our analyses, RPD was found in 18.4% of late AMD cases in Japanese. It was more common in eyes with RAP or atrophic AMD and was seldom found in PCV. ARMS2 A69S gene polymorphism was found more frequently in cases of exudative AMD with RPD, than in cases of exudative AMD without RPD. Eyes with RPD show a thin choroid and diminished vascular densities of choroidal vessels. PMID:27164756

  2. Changes in spectral properties and composition of lipofuscin fluorophores from human-retinal-pigment epithelium with age and pathology.

    PubMed

    Feldman, Tatiana B; Yakovleva, Marina A; Arbukhanova, Patimat M; Borzenok, Sergey A; Kononikhin, Alexey S; Popov, Igor A; Nikolaev, Evgeny N; Ostrovsky, Mikhail A

    2015-02-01

    Fundus autofluorescence mostly originates from bisretinoid fluorophores in lipofuscin granules, which accumulate in retinal-pigment-epithelium cells with age. The dynamics of accumulation, photo-oxidation, and photodegradation of bisretinoids during aging or in the presence of pathology have been insufficiently investigated. Changes in spectral properties and composition of human lipofuscin-granule fluorophores with age and pathology have now been investigated by a high-performance liquid chromatography method using spectrophotometric and fluorescent detectors connected in series. It was found that: (i) N-retinylidene-N-retinylethanolamine (A2E) fluorescence intensity is not predominant in the chloroform extract of human-cadaver-eye retinal pigment epithelium studied; bisretinoid photo-oxidation and photodegradation products have much higher fluorescent properties; (ii) the relative emission maximum in the fluorescence spectrum of suspended retinal-pigment-epithelium cells obtained from an individual human-cadaver eye without pathology is irrespective of donor age and falls within the range 575 ± 15 nm; in two cadaver eyes with signs of age-related macular degeneration, emission maxima were shifted by 23-36 nm towards the shortwave region; and (iii) the ratio of bisretinoid photo-oxidation and photodegradation products to unoxidized bisretinoids in the chloroform extract of cadaver-eye retinal pigment epithelium increases with donor age, from 0.69 ± 0.03 to 1.32 ± 0.04. The differences in fluorescence properties between chloroform extracts obtained from cadaver eyes with and without signs of age-related macular degeneration could be used to increase the potential of fundus autofluorescence imaging as a noninvasive diagnostic method. PMID:25471291

  3. Aqueous Cytokines as Predictors of Macular Edema in Patients with Diabetes following Uncomplicated Phacoemulsification Cataract Surgery

    PubMed Central

    Dong, Ning; Xu, Bing; Wang, Bingsong; Chu, Liqun; Tang, Xin

    2015-01-01

    This study aims to ascertain whether cytokines in the aqueous humor can predict macular edema (ME) in diabetic patients following uncomplicated phacoemulsification cataract surgery. Undiluted aqueous humor samples were obtained from 136 consecutive type 2 diabetic patients who underwent cataract surgery. The concentrations of 27 cytokines were measured in aqueous humor using the multiplex bead immunoassay. At the final follow-up examination, 116 patients completed 4 weeks of follow-up, and the incidence of macular edema was 29.31% (34 patients) 4 weeks after cataract surgery. Compared to the ME (−) patients, the concentrations of interleukin-1β (IL-1β) (P < 0.001), IL-6 (P < 0.001), IL-8 (P < 0.001), interferon-induced protein-10 (IP-10) (P = 0.003), monocyte chemotactic protein-1 (MCP-1) (P < 0.001), and vascular endothelial growth factor (VEGF) (P < 0.001) in the ME (+) patients were significantly higher. In addition, the aqueous levels of IL-1β (r = 0.288), IL-6 (r = 0.345), IL-8 (r = 0.256), IP-10 (r = 0.377), MCP-1 (r = 0.423), and VEGF (r = 0.279) were positively correlated with the postoperative foveal center point thickness (FCPT). However, the aqueous levels of IL-10 (P = 0.003) and IL-12 (P = 0.017) were significantly lower in patients with ME. These results suggest IL-1β, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, and VEGF may be potential predictors of postoperative macular thickness in patients with diabetes following uncomplicated phacoemulsification cataract surgery. PMID:25811020

  4. Acute retinal pigment epitheliitis: spectral domain optical coherence tomography, fluorescein angiography, and autofluorescence findings.

    PubMed

    Aydoğan, Tuğba; Güney, Esra; Akçay, Betül İlkay Sezgin; Bozkurt, Tahir Kansu; Ünlü, Cihan; Ergin, Ahmet

    2015-01-01

    A 17-year-old presented with central and paracentral scotomas in his right eye for one week. There was no remarkable medical or ocular history. Blood analyses were within normal range. At presentation both eyes' best-corrected visual acuities were 20/20. Slit-lamp examination result was normal. Fundus examination revealed yellow-white hypopigmented areas in the macula. Fluorescein angiography (FA) showed hypofluorescence surrounded by ring of hyperfluorescence. Fundus autofluorescence (FAF) was slightly increased. Spectral domain optical coherence tomography (SD-OCT) showed disruption of IS/OS junction with expansion of abnormal hyperreflectivity from retinal pigment epithelium to the outer nuclear layer (ONL). One month later fundus examination showed disappearance of the lesions. FA revealed transmission hyperfluorescence. FAF showed increased autofluorescence and pigment clumping. Hyperreflective band in SD-OCT disappeared. Loss of photoreceptor segment layers was observed in some of the macular lesions. The diagnosis of acute retinal pigment epitheliitis can be challenging after disappearance of fundus findings. FA, FAF, and SD-OCT are important tests for diagnosis after resolution of the disease. PMID:25767511

  5. 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

  6. Ocriplasmin-Induced Macular Hole Closure in the Absence of Vitreomacular Adhesion Release.

    PubMed

    Modi, Yasha S; Singh, Rishi P

    2015-06-01

    A 79-year-old man presented with a symptomatic, full-thickness macular hole with concurrent vitreomacular traction (VMT), stage 2. The patient was treated with a single injection of ocriplasmin. Within 1 week, the macular hole had closed, but there was persistence of vitreomacular traction. Two months after injection, the VMT released with sustained closure of the macular hole. The temporal course of macular hole closure antecedent to VMA release runs contrary to our current understanding of macular hole closure and warrants further research to decipher the mechanism by which ocriplasmin achieves its intended effect. PMID:26114851

  7. 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

  8. Ranibizumab in neovascular age-related macular degeneration

    PubMed Central

    Eng, Kenneth T; Kertes, Peter J

    2006-01-01

    Neovascular age-related macular degeneration (AMD) is a visually devastating condition resulting from choroidal neovascularization and secondary photoreceptor loss. Ranibizumab and bevacizumab are medications that target vascular endothelial growth factor (VEGF). While other therapies have demonstrated some ability to reduce the risk of losing vision from neovascular AMD, most patients continue to lose some degree of central visual acuity. There is growing evidence that intravitreal administration of ranibizumab and bevacizumab is effective in significantly improving the visual acuity in patients with neovascular age-related macular degeneration. PMID:18046922

  9. 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

  10. 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

  11. 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

  12. Altered cytokine profiles of human retinal pigment epithelium: Oxidant injury and replicative senescence

    PubMed Central

    Cao, Sijia; Walker, Gregory B.; Wang, Xuefeng; Cui, Jing Z.

    2013-01-01

    Purpose Age-related macular degeneration (AMD) is a local, chronic inflammatory disease of the eye that is influenced by oxidative stress and dysregulation of the retinal pigment epithelium (RPE) associated with aging. The purpose of this study is to characterize the effects of oxidative stress and replicative senescence on the secreted cytokine profiles of RPE in vitro. Methods We used multiple, serial passages of human RPE cells from primary culture as an in vitro model of aging. Responses of early passage 5 (P5) and late passage 21 (P21) RPE cells were compared. Oxidative stress was induced in RPE cells (P5) by exposure to 75 ?M hydroquinone (HQ) for 24 h. The secretome profiles of the RPE cells were measured with a multiplex suspension assay that assayed human cytokine, chemokine, and growth factors. Immunohistochemistry on younger (?55 years old) and older (?70 years old) human post-mortem donor eyes was used to verify selected cytokines. Results Supernatant of HQ-treated RPE cultures exhibited increased secreted levels of vascular endothelial growth factor (VEGF), interleukin (IL)-12, and IL-10 that reached statistical significance (p<0.05). Supernatant of late passage P21 RPE cultures exhibited decreased secreted levels of stromal cell-derived factor (SDF)-1?, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-8, IL-15, IL-6, and an increased level of IL-1ra compared to early passage P5 RPE cultures that reached statistical significance (p<0.05). Immunohistochemical analysis demonstrated increased expression of IL-1ra in RPE cells from older post-mortem donor eyes (?70 years old) versus younger eyes (?55 years old). Conclusions Our data demonstrate a unique cytokine secretion profile of primary culture RPE cells at early and late passage. Our in vitro data suggest an age-specific modulation of cytokine secretion in RPE and is consistent with immunohistochemical analysis on post-mortem eyes. The secretion profile associated with RPE under conditions that mimic oxidative stress, another factor associated with the pathogenesis of AMD, emphasizes upregulation of the angiogenic growth factor, vascular endothelial growth factor. Together, these data support the role of advanced age and oxidative stress in inflammatory cytokine modulation in RPE cells. PMID:23559866

  13. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2013-01-01

    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 (Congdon 2003). 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 To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 September 2011. 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 Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the analyses of 30 participants did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity at three months of treatment (decimal visual acuity 0.21± 0.56 in simvastatin and 0.19± 0.40 in placebo arm) or 45 days after the completion of treatment (decimal visual acuity 0.20± 0.50 in simvastatin and 0.19± 0.48 in placebo arm). The lens and retina status were unchanged during and after the treatment period for both groups. Of the ongoing trial, the preliminary analyses of 42 participants who completed 12 months follow-up did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity, drusen score or visual function (effect estimates and confidence intervals were not available). We contacted the investigators and will update the review as data become available. Authors' conclusions Evidence from currently available RCTs was insufficient to conclude that statins have any role in preventing or delaying the onset or progression of AMD. PMID:22419318

  14. Progressive macular hypomelanosis, excellent response with narrow-band ultraviolet B phototherapy.

    PubMed

    Montero, Laura Cuesta; Belinchón, Isabel; Toledo, Fernando; Betlloch, Isabel

    2011-06-01

    Progressive macular hypomelanosis (PMH) is an acquired disorder of skin pigmentation, which is mostly under-diagnosed. It is characterized by nummular hypopigmented lesions appearing on the trunk in young persons. Several treatment options are available, although topical clindamycin and benzoyl peroxide have been used traditionally. However, good results have recently been achieved using narrow-band ultraviolet B (NBUVB) phototherapy. We present the case of a 13-year-old girl with hypopigmented lesions on the trunk and limbs that had progressed over 1 year and that were diagnosed as PMH. The patient was initially treated with topical clindamycin and benzoyl peroxide. However, little improvement was seen and treatment was then started with NBUVB phototherapy. After 25 sessions, with a total cumulative dose of 18 J/cm(2) , the patient showed almost total repigmentation of the lesions. The treatment of PMH is often difficult, and very little is currently known about the treatment response in this disorder, as most reports have very small series of patients with a short disease progression time. NBUVB phototherapy has been shown to be effective, as seen in our patient, although in many cases, there is recurrence after the cessation of treatment. PMID:21535172

  15. Physics of Lipofuscin Formation and Growth in Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  16. 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. PMID:25609937

  17. 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

  18. Relationship between Outer Retinal Layers Thickness and Visual Acuity in Diabetic Macular Edema

    PubMed Central

    Wong, Raymond L. M.; Lee, Jacky W. Y.; Yau, Gordon S. K.; Wong, Ian Y. H.

    2015-01-01

    Purpose. To investigate the correlation of outer retinal layers (ORL) thickness and visual acuity (VA) in patients with diabetic macular edema (DME). Methods. Consecutive DME patients seen at the Retina Clinic of The University of Hong Kong were recruited for OCT assessment. The ORL thickness was defined as the distance between external limiting membrane (ELM) and retinal pigment epithelium (RPE) at the foveal center. The correlation between total retinal thickness, ORL thickness, and vision was calculated. Results. 78 patients with DME were recruited. The mean age was 58.1 years (±11.5 years) and their mean visual acuity measured with Snellen chart was 0.51 (±0.18). The correlation coefficient between total retinal thickness and visual acuity was 0.34 (P < 0.001) whereas the correlation coefficient was 0.65 between ORL thickness and visual acuity (P < 0.001). Conclusion. ORL thickness correlates better with vision than the total retinal thickness. It is a novel OCT parameter in the assessment of DME. Moreover, it could be a potential long term visual prognostic factor for patients with DME. PMID:26167510

  19. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

    PubMed Central

    Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD. PMID:24707498

  20. Recent developments in the management of dry age-related macular degeneration.

    PubMed

    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

  1. 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

  2. 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 more extensively evaluated current mETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice Modified ETDRS focal photocoagulation should continue as a standard approach for treating diabetic macular edema. PMID:17420366

  3. 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

  4. 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. PMID:26834454

  5. [Nutrition and age-related macular degeneration].

    PubMed

    Desmettre, T; Lecerf, J-M; Souied, E-H

    2004-11-01

    The nutritional factors involved in the pathogenesis of age-related macular degeneration (AMD) include antioxidants or antioxidant cofactors: vitamins A, C, etc.; zinc, etc.; anti-free-radicals such as beta-carotene and carotenoids, including lutein and zeaxanthin; micronutrients protecting from blue light such as lutein and zeaxanthin; and finally components of the membranes of the photoreceptors docosahexaenoic acid (DHA). These nutritional factors are closely related to environmental risk factors such as smoking and chronic blue light exposure. Although the experimental and epidemiological data are concordant and coherent, the protective role of these micronutrients is not clearly established, mainly because there are very few clinical studies. However, a first observation study showed positive effects at stages 3 and 4 of AMD. Report #8 of the Age-Related Eye Disease Study (AREDS) provides important results for preventing complications of AMD (secondary prevention), and the cocktail of micronutrients proposed even encourages complementary studies on, for example, lutein and zeaxanthin instead of beta-carotene. The outcome of observation studies including a supplementation of long-chain polyunsaturated fatty acids (PUFA) of the omega-3 family (DHA) is also important, as it addresses primary prevention of the disease. A supplementation of omega-3 PUFAs could be proposed to certain subjects at risk for AMD for primary prevention and a supplementation with an antioxidant cocktail of micronutrients could be proposed to patients presenting AMD at stages 3 or 4 or to subjects with a nutritional imbalance. These conceivable supplementations are compatible with simple dietary advice. The supplements currently proposed could be optimized to increase their advantages. New research and new clinical studies are necessary to definitively validate these formulations in order to grant them an authentic drug status. PMID:15602406

  6. Macular Thickness Variability in Primary Open Angle Glaucoma Patients using Optical Coherence Tomography

    PubMed Central

    Agarwal, Prakashchand; Sathyan, P; Saini, VK

    2014-01-01

    ABSTRACT Aim: To compare the difference of retinal macular thickness and macular volume using optical coherence tomography (OCT) in primary open angle glaucoma (POAG) patients with the normal subjects. Materials and methods: This observational case control study included primary open angle glaucoma (POAG) patients (n = 124 eyes) and healthy subjects in the control group (n = 124 eyes). All subjects underwent detailed history, general and systemic exami -nation. Complete ocular examination included best corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP), central corneal thickness, gonioscopy, dilated fundus biomicroscopy. Field analysis was done by white on white Humphrey Field Analyzer (Carl Zeiss). Optical coherence tomography imaging of macular area was performed using Stratus OCT (OCT 3, Version 4, Carl Zeiss Inc, Dublin, California, USA). In both these groups, parameters analyzed were macular thickness, inner macular thicknesses (IMT), outer macular thicknesses (OMT), central macular thick ness (CMT) and total macular volume (TMV). Results: The POAG group had significantly decreased values of TMV, OMT and IMT, compared to control group, while there was no difference in CMT, presumably due to absence of ganglion cells in the central part. Thus, macular thickness and volume parameters may be used for making the diagnosis of glaucoma especially in patients with abnormalities of disc. Conclusion: Macular thickness parameters correlated well with the diagnosis of glaucoma. How to cite this article: Sharma A, Agarwal P, Sathyan P, Saini VK. Macular Thickness Variability in Primary Open Angle Glaucoma Patients using Optical Coherence Tomography. J Current Glau Prac 2014;8(1):10-14.

  7. A colorimetric sensor array of porous pigments.

    PubMed

    Lim, Sung H; Kemling, Jonathan W; Feng, Liang; Suslick, Kenneth S

    2009-12-01

    The development of a low-cost, simple colorimetric sensor array capable of the detection and identification of toxic gases is reported. This technology uses a disposable printed array of porous pigments in which metalloporphyrins and chemically-responsive dyes are immobilized in a porous matrix of organically modified siloxanes (ormosils) and printed on a porous membrane. The printing of the ormosil into the membrane is highly uniform and does not lessen the porosity of the membrane, as shown by scanning electron microscopy. When exposed to an analyte, these pigments undergo reactions that result in well-defined color changes due to strong chemical interactions: ligation to metal ions, Lewis or Brønsted acid-base interactions, hydrogen bonding, etc. Striking visual identification of 3 toxic gases has been shown at the IDLH (immediately dangerous to life and health) concentration, at the PEL (permissible exposure level), and at a level well below the PEL. Identification and quantification of analytes were achieved using the color change profiles, which were readily distinguishable in a hierarchical clustering analysis (HCA) dendrogram, with no misclassifications in 50 trials. PMID:19918616

  8. A colorimetric sensor array of porous pigments

    PubMed Central

    Lim, Sung H.; Kemling, Jonathan W.; Feng, Liang

    2010-01-01

    The development of a low-cost, simple colorimetric sensor array capable of detection and identification of toxic gases is reported. This technology uses a disposable printed array of porous pigments in which metalloporphyrins and chemically responsive dyes are immobilized in a porous matrix of organically modified siloxanes (ormosils) and printed on a porous membrane. The printing of the ormosil into the membrane is highly uniform and does not lessen the porosity of the membrane, as shown by scanning electron microscopy. When exposed to an analyte, these pigments undergo reactions that result in well-defined color changes due to strong chemical interactions: ligation to metal ions, Lewis or Bronsted acid-base interactions, hydrogen bonding, etc. Striking visual identification of 3 toxic gases has been shown at the IDLH (immediately dangerous to life and health), at the PEL (permissible exposure level), and at a level well below the PEL. Identification and quantification of analytes were achieved using the color change profiles, which were readily distinguishable in a hierarchical clustering analysis (HCA) dendrogram, with no misclassifications in 50 trials. PMID:19918616

  9. An Update on Intravitreal Injections for Macular Diseases: Friend or Foe?

    PubMed

    Chan, Vesta C K; Liu, David T; Lam, Dennis S

    2012-01-01

    The purpose of this article is to review the role of intravitreal injections of medications in the treatment of the two common macular diseases, macular edema and age related macular degeneration (AMD). We perform literature search by search engine Pubmed till May 2011, using keywords 'intravitreal injections', 'age-related macular degeneration' and 'macular edema' to retrieve relevant review articles and original papers. To conclude, with advance in technology, intravitreal injections of medications may have become an integral part of our ability to treat a wide range of macular diseases. The use of ranibizumab, pegaptanib in the treatment of neovascular AMD and TA in the treatment of various causes of macular edema have shown promising results in a number of prospective randomized controlled trials, with low risk of complications reported. PMID:26107017

  10. Yellow corneal ring associated with vitamin supplementation for age-related macular degeneration

    PubMed Central

    Eller, Andrew W; Gorovoy, Ian R; Mayercik, Vera A

    2012-01-01

    Purpose To report the first described cases of peripheral yellow corneal rings secondary to vitamin supplementation for age-related macular degeneration (ARMD). Design Retrospective single-center case series. Participants The eyes of four patients taking vitamin supplementation for ARMD were examined at University of Pittsburgh Medical Center (UPMC) Department of Ophthalmology between January 2010 and April 2011. Methods We reviewed the medical records of four patients with peripheral corneal rings receiving vitamin supplementation for ARMD. Main Outcome Measures the presence of peripheral yellow corneal rings, skin findings, and serum carotene levels. Results Each patient had circumferential yellow peripheral corneal rings and exhibited subtle yellowing of the skin most notable on the palms. Serum carotene levels were normal in two of the three cases and markedly elevated in the last case in which it was measured. Conclusion It is unclear at this time how to counsel patients with this ocular finding. We suspect that these rings are more common than generally appreciated as they can have a subtle appearance or may be misdiagnosed as arcus senilis. We suggest that a formal study be performed on a cohort of patients taking macular degeneration vitamin supplementation that specifically screens for yellow rings and measures serum carotene levels when they are identified. PMID:22330962

  11. Effects of Bevacizumab on Bcl-2 Expression and Apoptosis in Retinal Pigment Epithelial Cells under Oxidative Stress

    PubMed Central

    Kim, Sukjin; Kim, Young Jun; Kim, Na Rae

    2015-01-01

    Purpose To evaluate the effects of bevacizumab on expression of B-cell leukemia/lymphoma (Bcl)-2 and apoptosis in retinal pigment epithelial (RPE) cells under oxidative stress conditions. Methods RPE cells were treated with H2O2 (0, 100, 200, 300, and 400 µM) and bevacizumab at or above the doses normally used in clinical practice (0, 0.33, 0.67, 1.33, and 2.67 mg/mL). Cell apoptosis was measured using flow cytometry with annexin V-fluorescein isothiocyanate. The expression of Bcl-2 mRNA was determined using reverse transcription polymerase chain reaction. Results Under low oxidative stress conditions (H2O2 100 µM), cell apoptosis was not significantly different at any concentration of bevacizumab, but Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL). Under moderate oxidative stress conditions (H2O2 200 µM), Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL), but cell apoptosis increased only at 2.67 mg/mL of bevacizumab. Under high oxidative stress (300 µM) conditions, cell apoptosis increased at high concentrations of bevacizumab (1.33 and 2.67 mg/mL), but it did not correlate with Bcl-2 expression. Conclusions Withdrawal of vascular endothelial growth factor can lead to RPE cell apoptosis and influences the expression of anti-apoptotic genes such as Bcl-2 under oxidative stress conditions. Since oxidative stress levels of each patient are unknown, repeated injections of intravitreal bevacizumab, as in eyes with age-related macular degeneration, might influence RPE cell survival. PMID:26635460

  12. Clinicopathologic correlate of a fresh eyelid pigment implantation

    SciTech Connect

    Tse, D.T.; Folberg, R.; Moore, K.

    1985-10-01

    An eyelid with freshly applied black eyeliner pigment was examined histologically. X-ray microanalysis of the pigment suspension from the manufacturer's vial indicated that its composition was 98% iron and 2% titanium. Transmission electron microscopic examination disclosed that particles were in the extracellular matrix; intracellular particles were not seen. By light microscopy, implant material was detected in various levels of the dermis and was found in dermal lymphatics as well as within and surrounding a hair follicle. This study suggests that systemic exposure to the implant material is possible and offers explanations for permanent eyelash loss, which the authors have seen following this procedure.

  13. Vestibular Dysfunction, Altered Macular Structure and Trait Localization in A/J Inbred Mice

    PubMed Central

    Vijayakumar, Sarath; Lever, Teresa E.; Pierce, Jessica; Zhao, Xing; Bergstrom, David; Lundberg, Yunxia Wang; Jones, Timothy A.; Jones, Sherri M.

    2015-01-01

    A/J mice develop progressive hearing loss that begins before one month of age and is attributed to cochlear hair cell degeneration. Screening tests indicated 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, SEM, TEM, 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/6J). 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 17A/J/NaJ), thus indicating that Chr 17A/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 study of mechanisms underlying otoconial formation and maintenance. PMID:25645995

  14. Interobserver Agreement in Detecting Spectral-Domain Optical Coherence Tomography Features of Diabetic Macular Edema

    PubMed Central

    Heng, Ling Zhi; Pefianaki, Maria; Hykin, Philip; Patel, Praveen J.

    2015-01-01

    Purpose To evaluate interobserver agreement for the detection of spectral-domain optical coherence tomography (SDOCT) features of diabetic macular edema (DME). Method Cross-sectional study in which 2 retinal specialists evaluated SDOCT scans from eyes receiving treatment for DME. Scans from 50 eyes with DME of 39 patients were graded for features of DME including intra-retinal fluid (IRF), diffuse retinal oedema (DRE), hyper-reflective foci (HRF), subretinal fluid (SRF), macular fluid and vitreomacular traction (VMT). Features were graded as present or absent at zones involving the fovea, 1mm from the fovea and the whole scan of 49 line scans. Analysis was performed using cross-tabulations for percentage concordance and kappa values (κ). Results In the 2950 line scans analysed, there was an increase in percentage concordance for DRE and HRF when moving from a foveal line scan, 1mm zone and then to a whole scan analysis (88% vs 94% vs 96%) and (88% vs 94% vs 94%) respectively with κ ranging from substantial to almost perfect. Percentage concordance for SRF was 96% at all 3 regions analysed, whilst IRF was 96% at fovea and 98% at higher number of line-scans analysed. Concordance for MF was 100% at fovea and 98% at 1mm zone and whole scan with almost perfect and substantial κ respectively. κ agreement was substantial for VMT at all regions analysed. Conclusion We report a high level of interobserver agreement in the detection of SDOCT features of DME. This finding is important as detection of macular fluid is used to guide retreatment with anti-angiogenic agents. PMID:25996150

  15. 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 study of mechanisms underlying otoconial formation and maintenance. PMID:25645995

  16. Anti-vascular endothelial growth factor therapy for diabetic macular edema

    PubMed Central

    Hopkins, J. Jill; Sorof, Jonathan; Ehrlich, Jason S.

    2013-01-01

    Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR. The historic standard of care for DME has been macular laser photocoagulation, which has been shown to stabilize vision and reduce the rate of further vision loss by 50%; however, macular laser leads to significant vision recovery in only 15% of treated patients. Mechanisms contributing to the microvascular damage in DR and DME include the direct toxic effects of hyperglycemia, sustained alterations in cell signaling pathways, and chronic microvascular inflammation with leukocyte-mediated injury. Chronic retinal microvascular damage results in elevation of intraocular levels of vascular endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific mitogen that mediates many important physiologic processes, including but not limited to the development and permeability of the vasculature. The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF, each administered by intraocular injection, have been tested in prospective, randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation, and avoid the ocular side effects associated with laser treatment. Thus, anti-VEGF therapy has become the preferred treatment option for the management of DME in many patients. PMID:24324855

  17. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    PubMed Central

    Fong, Angie HC; Lai, Timothy YY

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

  18. 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. PMID:25576667

  19. Nylon friction dermatitis: A distinct subset of macular amyloidosis.

    PubMed

    Somani, V K; Hari, S; Sita, V N; Razvi, F

    1995-01-01

    43 patients were taken up for the study, all of whom were asymptomatic and presented with bluish black pigmentation. 23 patients presented with pigmentation which was proximal and distal to the bony prominences, all of whom gave a history of using nylon scrubbers during bathing. 20 patients gave no history of friction and the pigmentation was present on the extensor forearms, shins and upper back. Histopathological examination confirmed amyloid deposits. PMID:20952929

  20. Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration.

    PubMed

    Kurihara, Toshihide; Westenskow, Peter D; Gantner, Marin L; Usui, Yoshihiko; Schultz, Andrew; Bravo, Stephen; Aguilar, Edith; Wittgrove, Carli; Friedlander, Mollie Sh; Paris, Liliana P; Chew, Emily; Siuzdak, Gary; Friedlander, Martin

    2016-01-01

    Photoreceptors are the most numerous and metabolically demanding cells in the retina. Their primary nutrient source is the choriocapillaris, and both the choriocapillaris and photoreceptors require trophic and functional support from retinal pigment epithelium (RPE) cells. Defects in RPE, photoreceptors, and the choriocapillaris are characteristic of age-related macular degeneration (AMD), a common vision-threatening disease. RPE dysfunction or death is a primary event in AMD, but the combination(s) of cellular stresses that affect the function and survival of RPE are incompletely understood. Here, using mouse models in which hypoxia can be genetically triggered in RPE, we show that hypoxia-induced metabolic stress alone leads to photoreceptor atrophy. Glucose and lipid metabolism are radically altered in hypoxic RPE cells; these changes impact nutrient availability for the sensory retina and promote progressive photoreceptor degeneration. Understanding the molecular pathways that control these responses may provide important clues about AMD pathogenesis and inform future therapies. PMID:26978795

  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. 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

  3. 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…

  4. 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...

  5. Treatment of dry age-related macular degeneration with dobesilate

    PubMed Central

    Cuevas, P; Outeirio, L A; Angulo, J; Gimnez-Gallego, G

    2012-01-01

    The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337

  6. NUTRITIONAL SUPPLEMENTATION, CATARACTS AND AGE-RELATED MACULAR DEGENERATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related cataract and age-related macular degeneration (AMD) are the major causes of visual impairment and blindness in the aging population. Specific nutrients in the diet that are thought to be important in the prevention of these diseases are vitamins C and E, the carotenoids, lutein and zeaxa...

  7. Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema

    PubMed Central

    Diaz-Llopis, Manuel; Udaondo, Patricia; Millán, Jose Maria; Arevalo, J Fernando

    2013-01-01

    The aim of this paper is to determine the role of enzymatic vitrectomy performed by intravitreal injection of autologous plasmin enzyme (APE) in the management of diabetic retinopathy and diabetic macular edema (DME). Diabetic patients with proliferative diabetic retinopathy or DME and evident posterior hyaloid adherence to the retinal surface were included. All cases were treated with an initial intravitreal injection of APE and reevaluated one month later, measuring changes in best-corrected visual acuity (BCVA), macular thickness and the status of the posterior hyaloid. A second APE injection was performed in cases with no evident posterior vitreous detachment (PVD) after the initial treatment. Sixty-three eyes were included in the present review. A complete PVD appeared in 38% of cases (24 eyes) after one injection of plasmin and the total increased to 51% (32 eyes) after the second injection, separated at least by one month. The central macular thickness improved in all cases (100%) and BCVA in 89%. Finally, in 50% of eyes with proliferative diabetic retinopathy, a high reduction of new vessels regression was observed. Enzymatic vitrectomy could be considered a good therapeutic alternative in diabetic retinopathy and macular edema. PMID:24379923

  8. The Evolving Treatment Options for Diabetic Macular Edema

    PubMed Central

    Jain, Atul; Varshney, Neeta; Smith, Colin

    2013-01-01

    Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults, and diabetic macular edema (DME) is the most common cause of visual impairment in individuals with DR. This review focuses on the pathophysiology, previous treatment paradigms, and emerging treatment options in the management of DME. PMID:24106640

  9. Pigmented paravenous retinochoroidal atrophy (Review)

    PubMed Central

    HUANG, HOU-BIN; ZHANG, YI-XIN

    2014-01-01

    Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon disease characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinochoroidal atrophy that are distributed along the retinal veins. Patients are usually asymptomatic and the disease process is non-progressive or slow and subtly progressive. It is commonly bilateral and symmetric. The cause of the condition may be unknown or idiopathic, although a dysgenetic, degenerative, hereditary etiology or even an inflammatory cause has been hypothesized. A non-inflammatory cause is referred to as primary, while inflammation-associated PPRCA is referred to as secondary or pseudo PPRCA. The present study reviewed and summarized the features of PPRCA. PMID:24926324

  10. 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.

  11. Nanoscience of an ancient pigment.

    PubMed

    Johnson-McDaniel, Darrah; Barrett, Christopher A; Sharafi, Asma; Salguero, Tina T

    2013-02-01

    We describe monolayer nanosheets of calcium copper tetrasilicate, CaCuSi(4)O(10), which have strong near-IR luminescence and are amenable to solution processing methods. The facile exfoliation of bulk CaCuSi(4)O(10) into nanosheets is especially surprising in view of the long history of this material as the colored component of Egyptian blue, a well-known pigment from ancient times. PMID:23215240

  12. Human skin pigmentation, migration and disease susceptibility

    PubMed Central

    Jablonski, Nina G.; Chaplin, George

    2012-01-01

    Human skin pigmentation evolved as a compromise between the conflicting physiological demands of protection against the deleterious effects of ultraviolet radiation (UVR) and photosynthesis of UVB-dependent vitamin D3. Living under high UVR near the equator, ancestral Homo sapiens had skin rich in protective eumelanin. Dispersals outside of the tropics were associated with positive selection for depigmentation to maximize cutaneous biosynthesis of pre-vitamin D3 under low and highly seasonal UVB conditions. In recent centuries, migrations and high-speed transportation have brought many people into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks. These have been increased by urbanization and changes in diet and lifestyle. Three examples—nutritional rickets, multiple sclerosis (MS) and cutaneous malignant melanoma (CMM)—are chosen to illustrate the serious health effects of mismatches between skin pigmentation and UVR. The aetiology of MS in particular provides insight into complex and contingent interactions of genetic and environmental factors necessary to trigger lethal disease states. Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty-first century. PMID:22312045

  13. 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

  14. Bidirectional reflectance from pigmented coatings

    NASA Astrophysics Data System (ADS)

    Raven, Peter N.; Watson, Rupert M. J.; Williams, John W.; Milne, Paul E. Y.

    1999-10-01

    There has been increasing interest in the measurement, validation, and parameterization of the bidirectional reflectance distribution function (BRDF) from surface coatings for image simulation and rendering, and design models of coating systems. The complexity of data required depends on the finish or final appearance of the surface coating. In particular the development of optical effect pigments places heightened requirements on the BRDF data needed for adequate characterization of a surface coating. Measurements of the BRDF are presented from pigmented films representative of the top layer of a paint coating. The measurements investigate the scattering characteristics of pearlescent pigments as a function of the incident polar angle and the polar and azimuthal scatter angles, including a study of the spectral variation of the BRDF across the visible waveband from 350 nm to 800 nm. In addition, measurements of linearly polarized BRDF as a function of incident and reflected directions are reported. The measurements emphasize the various optical properties of coatings such as surface and volume scattering and polarization contributions, which need to be considered if the data is to be accurately modelled or parameterized and used effectively.

  15. Characteristics of Fixational Eye Movements in People With Macular Disease

    PubMed Central

    Kumar, Girish; Chung, Susana T. L.

    2014-01-01

    Purpose. Fixation stability is known to be poor for people with macular disease and has been suggested as a contributing factor for the poor visual performance of these individuals. In this study, we examined the characteristics of the different components of fixational eye movements and determined the component that plays a major role in limiting fixation stability in people with macular disease. Methods. Sixteen observers with macular disease and 14 older adults with normal vision (control observers) monocularly fixated a small cross presented using a Rodenstock scanning laser ophthalmoscope, for trials of 30 seconds. The retinal image and the position of the cross on the retina were recorded digitally. Eye movements were extracted from the recorded videos at a sampling rate of 540 Hz using a cross-correlation technique. A velocity criterion of 8°/s was used to differentiate between slow drifts and microsaccades. Results. Observers with macular disease demonstrated higher fixation instability, larger amplitudes of slow drifts and microsaccades, and lower drift velocities, when compared with older adults with normal vision. The velocity and the rate of microsaccades were comparable between the two groups of observers. Multiple linear regression analysis showed that the amplitude of microsaccades, and to a smaller extent, the amplitude of slow drifts, play a major role in limiting fixation stability. Conclusions. Fixation stability in people with macular disease is primarily limited by the amplitude of microsaccades, implying that rehabilitative strategies targeted at reducing the amplitude of microsaccades should improve fixation stability, and may lead to improved visual functions. PMID:25074769

  16. Antibacterial Activity of Red Pigment Produced by Halolactibacillus alkaliphilus MSRD1--an Isolate from Seaweed.

    PubMed

    Suresh, Murugan; Renugadevi, B; Brammavidhya, S; Iyapparaj, Palanisamy; Anantharaman, Perumal

    2015-05-01

    The present study was carried out with the aim to isolate an antibacterial pigment from seaweed-associated bacterium. The bacterium was identified as Halolactibacillus alkaliphilus MSRD1 by 16S rRNA sequencing. The isolated bacterium was cultured in 50% Luria-Bertani seawater broth (LB-SWB) with 1% glycerol. The pigment was extracted with 99% ethanol and analyzed by UV-Vis spectroscopy at 490 nm. The candidate bacterium was optimized with various NaCl concentrations from 5 to 20%. The results inferred that the bacterium produce maximum pigment at 5% NaCl level. The candidate bacterium H. alkaliphilus MSRD1 was found to be producing the maximum pigment during the 120-h incubation. The protein content of the pigment was found to be maximum of 72% at the end of the 120-h incubation. The extracted pigment was stable up to 80 °C, pink at acidic pH (1 to 5) and orange at basic pH (8 to 12). The isolated pigment was fractionated by silica gel column chromatography. Fractionated pigment was characterized by TLC, FT-IR, and SDS-PAGE. In the antibacterial context, the pigment was highly inhibited Staphylococcus aureus and Salmonella typhi with the zone of inhibition 16 and 14 mm, respectively. According to SDS-PAGE, the size of the pigment was approximately 80 kDa. The H. alkaliphilus MSRD1 has high capacity to produce the pigment with antibacterial properties. This could be effectively used in the future. PMID:25795062

  17. 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 included studies. Main results Two RCTs with 144 total participants met the selection criteria. Both trials compared simvastatin versus placebo in older people (> 50 or 60 years) with high risk of developing AMD (drusen present on examination). The larger trial with 114 participants was conducted in Australia and used a higher dose (40 mg daily) of simvastatin for three years. Participants and study personnel in this trial were adequately masked; however, data were missing for 30% of participants at three years follow-up. The smaller trial of 30 participants was conducted in Italy and used a lower dose (20 mg) of simvastatin for three months. This trial reported insufficient details to assess the risk of bias. Neither trial reported data for change in visual acuity. Analysis of 30 participants in the smaller trial did not show a statistically significant difference between the simvastatin and placebo groups in visual acuity values at three months of treatment (decimal visual acuity 0.21 ± 0.56 in simvastatin group and 0.19 ± 0.40 in placebo group) or 45 days after the completion of treatment (decimal visual acuity 0.20 ± 0.50 in simvastatin group and 0.19 ± 0.48 in placebo group). The lack of a difference in visual acuity was not explained by lens or retina status, which remained unchanged during and after the treatment period for both groups. Preliminary analyses of 42 participants who had completed 12 months follow-up in the larger trial did not show a statistically significant difference between simvastatin and the placebo groups for visual acuity, drusen score, or visual function (effect estimates and confidence intervals were not available). Complete data for these outcomes at three years follow-up were not reported. At three years, the effect of simvastatin in slowing progression of AMD compared with placebo was uncertain (odds ratio 0.51, 95% confidence interval 0.23 to 1.09). One trial did not report adverse outcomes. The second trial reported no difference between groups in terms of adverse events such as death, muscle aches, and acute hepatitis. Authors’ conclusions Evidence from currently available RCTs is insufficient to conclude that statins have a role in preventing or delaying the onset or progression of AMD. PMID:25675254

  18. The retinal pigment epithelium undergoes massive apoptosis during early differentiation and pigmentation of the optic cup

    PubMed Central

    Pequignot, M.O.; Provost, A.C.; Sallé, S.; Menasche, M.; Saule, S.; Jaïs, J-P.

    2011-01-01

    Purpose The aim of our work was to study apoptosis during the development of the retinal pigment epithelium (RPE) in mice between embryonic day (E) 10.5 and E12.5 and to examine a possible link between apoptosis and pigmentation. Methods We collected mouse embryos at E10.5, E11.5, and E12.5 and labeled apoptotic cells in 5-µm paraffin sections, using the terminal deoxynucleotidyl transferase dUTP nick end labeling technique. We counted the total number of cells and the number of apoptotic cells in the early developing RPE and calculated the percentage of apoptosis at each stage. Results In the C57BL/6J mouse, 17% of the RPE cells were apoptotic at E10.5 compared to 0.9% at E12.5. At E11.5, three-quarters of the RPE cells began to pigment, and apoptotic cells were located mostly in the nonpigmented part. In contrast, in the BALB/c mouse (tyrosinase-deficient) and pJ mouse (carrying mutations in the p gene) hypopigmented strains, the RPE contained significantly fewer apoptotic cells (7.5% and 10.1%, respectively) at E10.5 than controls. Subsequently at E11.5 and E12.5, the two hypopigmented strains displayed different apoptotic patterns; the BALB/c RPE had a similar percentage of apoptotic cells to controls (1.5% and 1.1%, respectively, for BALB/c versus 3.0% and 0.9%, respectively, for C57BL/6J), whereas the pJ RPE contained significantly more apoptosis (7.5% and 3.5%, respectively). Overall we observed differences in the evolution of the relative total number of RPE cells between the three strains. Conclusions Apoptosis is a main event during the first stages of normal RPE development, indicating an essential role during RPE differentiation. Moreover, the early apoptotic pattern and possibly the whole early development of the RPE is different between hypopigmented and pigmented strains, as well as between BALB/c and pJ mice. This suggests the existence of regulatory and developmental differences with a more complex origin than just differing pigmentation levels. PMID:21541273

  19. Macular ganglion cell-inner plexiform layer thinning in patients with visual field defect that respects the vertical meridian.

    PubMed

    Shin, Hye-Young; Park, Hae-Young Lopilly; Choi, Jin-A; Park, Chan Kee

    2014-09-01

    The aim of this work is to compare the thinning patterns of the ganglion cell inner-plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) as measured using Cirrus high-definition optical coherence tomography (HD-OCT) in patients with visual field (VF) defects that respect the vertical meridian. Twenty eyes of 11 patients with VF defects that respect the vertical meridian were enrolled retrospectively. The thicknesses of the macular GCIPL and pRNFL were measured using Cirrus HD-OCT. The 5 and 1% thinning area index (TAI) was calculated as the proportion of abnormally thin sectors at the 5 and 1% probability level within the area corresponding to the affected VF. The 5 and 1% TAI were compared between the GCIPL and pRNFL measurements. The color-coded GCIPL deviation map showed a characteristic vertical thinning pattern of the GCIPL, which is also seen in the VF of patients with brain lesions. The 5 and 1% TAI were significantly higher in the GCIPL measurements than in the pRNFL measurements (all p < 0.01). Macular GCIPL analysis clearly visualized a characteristic topographic pattern of retinal ganglion cell (RGC) loss in patients with VF defects that respect the vertical meridian, unlike pRNFL measurements. Macular GCIPL measurements provide more valuable information than pRNFL measurements for detecting the loss of RGCs in patients with retrograde degeneration of the optic nerve fibers. PMID:25104464

  20. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1?year after a single intravitreal injection of dobesilate

    PubMed Central

    Cuevas, P; Outeirio, L A; Azanza, C; Gimnez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60?years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1?year after a single intravitreal injection of dobesilate. PMID:24225910

  1. Tattoo pigment in sentinel lymph nodes: a mimicker of metastatic malignant melanoma.

    PubMed

    Chikkamuniyappa, Shylashree; Sjuve-Scott, Rolf; Lancaster-Weiss, Kris; Miller, Alexander; Yeh, I-Tien

    2005-01-01

    Tattoo pigment in the sentinel lymph nodes of melanoma patients represents a clinical challenge. If a tattoo is present in the area of the primary melanoma, the draining lymph nodes are likely to contain tattoo pigment, as well as being the site for metastatic deposits of melanoma. We describe a case report involving an elderly Caucasian male diagnosed with a Clark level-4 nodular malignant melanoma, wherein intraoperatively we encounter a darkly pigmented lymph node highly suspicious for metastatic disease. The patient had a tattoo in the vicinity of the malignant melanoma The specimen is sent for histological examination and is found to contain pigmented macrophages, but metastatic malignant melanoma is not identified. Histological confirmation of an enlarged pigmented node is essential before radical surgery is performed. PMID:15748555

  2. 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-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD. PMID:24679442

  3. Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials

    PubMed Central

    Daniel, Ebenezer; Toth, Cynthia A.; Grunwald, Juan E.; Jaffe, Glenn J.; Martin, Daniel F.; Fine, Stuart L.; Huang, Jiayan; Ying, Gui-shuang; Hagstrom, Stephanie A.; Winter, Katrina; Maguire, Maureen G.

    2013-01-01

    Objective To describe risk factors for scar in eyes treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD). Design Prospective cohort study within a randomized clinical trial. Participants Patients with no scar on color fundus photography (CFP) or fluorescein angiography (FA) at enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Methods Eyes were assigned to ranibizumab or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked readers assessed CFP and FA. Baseline demographic characteristics, visual acuity, morphologic features on photography and optical coherence tomography (OCT), and genotypes associated with AMD risk were evaluated as risk factors using adjusted hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were classified as fibrotic with well-demarcated elevated mounds of yellowish white tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying amounts of central depigmentation. Main Outcome Measures Scar formation. Results Scar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline characteristics associated with greater risk of scarring were predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4–3.9) versus occult CNV, blocked fluorescence (aHR, 1.4; CI, 1.1–1.8), foveal retinal thickness >212 μm (aHR, 2.4; CI, 1.7–3.6) versus <120 μm, foveal subretinal tissue complex thickness >275 μm (aHR, 2.4; CI, 1.7–3.6) versus ≤75 μm, foveal subretinal fluid (aHR, 1.5; CI, 1.1–2.0) versus no subretinal fluid, and subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3–2.3) versus no SHRM. Eyes with elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5–0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically significant association with scarring. Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the scar types were similar except that eyes with larger lesion size or visual acuity <20/40 were more likely to develop fibrotic scars. Conclusions Approximately half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic neovascularization, a thicker retina, and more fluid or material under the foveal center of the retina are more likely to develop scar. PMID:24314839

  4. Optical Coherence Tomography grading reproducibility during the Comparison of Age-Related Macular Degeneration Treatments Trials

    PubMed Central

    DeCroos, Francis Char; Toth, Cynthia A.; Stinnett, Sandra S.; Heydary, Cynthia S.; Burns, Russell; Jaffe, Glenn J.

    2013-01-01

    OBJECTIVE To report Reading Center reproducibility during grading of Optical Coherence Tomography (OCT, Carl Zeiss Meditec, Dublin, California) images obtained during the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). DESIGN Prospective clinical trial PARTICIPANTS Independent reading teams reevaluated 270 OCT scans randomly sampled from the first 2 years of CATT enrollment. To assess temporal drift, a cohort of 23 scans submitted during the initial portion of the CATT study was longitudinally followed with serial reproducibility analysis. INTERVENTION CATT readers performed standardized grading on OCT images. A reader team, composed of two independent readers and a Senior Reader, evaluated each scan. Grading included the CATT OCT endpoints of total thickness at the foveal center point and intraretinal fluid, subretinal fluid, and sub-retinal pigment epithelium (RPE) fluid. Independent reading teams masked to the results of initial grading reevaluated scans to determine reproducibility of qualitative grading and measurements. MAIN OUTCOME MEASURES Categorical grading agreement was reported using percent agreement and kappa statistic and measurement agreement was reported using intraclass correlations and paired differences. RESULTS Reading Center teams reproducibly graded intraretinal fluid (percent agreement = 73%, kappa = 0.48, 95% confidence interval or CI 0.38 to 0.58), subretinal fluid (percent agreement = 90%, kappa = 0.80, 95% CI 0.73 to 0.87), and sub-RPE fluid (percent agreement 88%, kappa = 0.75, 95% CI 0.67 to 0.83). For independent Reading Center team measurements of total thickness at the foveal center point, the intraclass correlation was 0.99 (95% CI 0.99 to 0.99, and the mean paired difference between Reading Center teams was −4 micrometers (95% limits of agreement −55 to 47 micrometers). There was no qualitative or quantitative grading drift. CONCLUSIONS The standardized protocols used to evaluate OCT scans from the CATT study were reproducible. The methods used are suitable to monitor OCT imaging data from a large neovascular age related macular degeneration interventional multicenter study. PMID:22939114

  5. Effect of aflibercept in patients with age-related macular degeneration.

    PubMed

    Okuma, Hiroko; Mimura, Tatsuya; Goto, Mari; Kamei, Yuko; Yoshida, Maiko; Kondo, Aki; Matsubara, Masao

    2016-04-01

    The purpose of this study was to evaluate the efficacy of standard induction therapy with intravitreal aflibercept (IVA) in patients with exudative age-related macular degeneration (AMD) at 6 months after completion of induction therapy. Eleven eyes with typical AMD (tAMD) and 13 eyes with polypoidal choroidal vasculopathy (PCV) received three monthly doses of IVA (2 mg/0.05 ml in weeks 0, 4, and 8) for treatment of exudative AMD. Best-corrected visual acuity (BCVA) was measured, and optical coherence tomography was performed at baseline and at each monthly visit until 6 months after IVA. Treatment failure was defined as persistent or recurrent AMD that presented with cystoid macular edema, serous retinal detachment, and pigment epithelium detachment. Mean logMAR BCVA was improved from 0.62 ± 0.46 at baseline to 0.54 ± 0.43 at 6 months after IVA (p < 0.05). The success rate was 95.8 % at 3 months and 75.0 % at 6 months after IVA. Failure of IVA was positively associated with the absence of PVD before treatment (r = 0.35) and with the AMD type (tAMD, r = 0.43) by univariate analysis. Cox proportional hazards analysis demonstrated that the absence of PVD before treatment was associated with an increased risk of failure of IVA (OR = 33.17, p = 0.0219). Three months of induction IVA achieved a high success rate in patients with AMD monitored for up to 6 months. Factors associated with failure of IVA were the absence of PVD and the presence of tAMD. Accordingly, continuation of IVA following induction therapy may be beneficial to manage AMD in patients with tAMD or those without PVD. PMID:26043678

  6. 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

  7. Risk Factors for Refractory Diabetic Macular Oedema after Sub-Tenon's Capsule Triamcinolone Acetonide Injection

    PubMed Central

    Oshitari, Toshiyuki; Kitamura, Yuta; Nonomura, Sakiko; Arai, Miyuki; Takatsuna, Yoko; Sato, Eiju; Baba, Takayuki; Yamamoto, Shuichi

    2015-01-01

    The purpose of this study is to identify the risk factors for a recurrence or persistence of diabetic macular oedema (DME) after a sub-Tenon's capsule triamcinolone acetonide (STTA) injection. The medical records of 124 patients (124 eyes) treated by STTA were reviewed. The age, sex, HbA1c level, best-corrected visual acuity, central macular thickness, insulin use, pioglitazone use, systemic hypertension, serous retinal detachment, proteinuria, panretinal photocoagulation, microaneurysm photocoagulation (MAPC), subthreshold micropulse diode laser photocoagulation (SMDLP), cataract surgery, and history of vitrectomy were examined by logistic regression analysis. Procedures of MAPC and SMDLP were significantly associated with DME treated with STTA (P = 0.0315, P = 0.04, resp.). However, a history of vitrectomy was found to have significantly fewer recurrences or persistent DME after STTA (P = 0.0464). In conclusion, patients who required combined MAPC or SMDLP with a STTA injection had significantly higher refractoriness to STTA, but postvitrectomy may prevent the recurrence or persistence of DME after STTA injection. PMID:26457195

  8. OCT findings in macular hole formation in eyes with complete vitreofoveal separation.

    PubMed

    Targino, Abelardo; Costa, Rogério A; Calucci, Daniela; Cardillo, José A; Jorge, Rodrigo; Scott, Ingrid U

    2008-01-01

    The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes. PMID:18254356

  9. Microperoxisomes in retinal pigment epithelium.

    PubMed

    Robison, W G; Kuwabara, T

    1975-11-01

    Microperoxisomes were found to be abundant in the retinal pigment epithelium of the human, rhesus monkey, mice, rats, domestic fowl, and frog by ultrastructural histochemistry. They were rare in other cells of the retina and choroid. These organelles had a granular matrix, ranged in diameter from 0.15 mum to 0.30 mum, and were bound by a single tripartite membrane which often maintained slender connections with the smooth endoplasmic reticulum and other microperoxisomes. They exhibited a positive reaction (electron opaque product) following incubation in diaminobenzidine and H2O2 for the demonstration of the peroxidatic activity of catalase (Novikoff et al., J. Histochem. Cytochem. 20: 1006, 1972). The reaction was inhibited by: (1) aminotriazole; (2) dichlorophenol-indophenol; (3) preheating at 95 degrees C.; or (4) elimination of H2O2. Microperoxisomes, like the well-known peroxisomes (microbodies) of liver cells have been inplicated in various aspects of lipid metabolism and the detoxification of H2O2. We demonstrated for the first time that microperoxisomes respond to drug-induced changes in lipid metabolism, as previously shown for peroxisomes. Nafenopin is a recently utilized drug which greatly decreases serum lipids, increases hepatic catalase activity, and induces an increased size and number of hepatic peroxisomes. Black, beige, albino, and obese mutant mice of the C57BL/6J strain treated with nafenopin for several weeks showed a two- to threefold increase in the number of microperoxisomes in the retinal pigment epithelium. Microperoxisomes of the retinal pigment epithelium may be involved in the transport, storage, and rapid turnover of lipids associated with the maintenance of photoreceptor outer segment disc membranes. PMID:810456

  10. 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.

  11. Pigmented lesion of buccal mucosa.

    PubMed

    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

  12. 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.

  13. Preservation of the Photoreceptor Inner/Outer Segment Junction in Dry Age-Related Macular Degeneration Treated by Rheohemapheresis

    PubMed Central

    Rencová, Eva; Bláha, Milan; Studnička, Jan; Bláha, Vladimír; Lánská, Miriam; Renc, Ondřej; Stepanov, Alexander; Kratochvílová, Věra; Langrová, Hana

    2015-01-01

    Aim. To evaluate the long-term effect of rheohemapheresis (RHF) treatment of age-related macular degeneration (AMD) on photoreceptor IS/OS junction status. Methods. In our study, we followed 24 patients with dry AMD and drusenoid retinal pigment epithelium detachment (DPED) for a period of more than 2.5 years. Twelve patients (22 eyes) were treated by RHF and 12 controls (18 eyes) were randomized. The treated group underwent 8 RHF standardized procedures. We evaluated best-corrected visual acuity, IS/OS junction status (SD OCT), and macular function (multifocal electroretinography) at baseline and at 2.5-year follow-up. Results. RHF caused a decrease of whole-blood viscosity/plasma viscosity at about 15/12%. BCVA of treated patients increased insignificantly (P = 0.187) from median 74.0 letters (56.2 to 81.3 letters) to median 79.0 letters (57.3 to 83.4 letters), but it decreased significantly from 74.0 letters (25.2 to 82.6 letters) to 72.5 letters (23.4 to 83.1 letters) in the control group (P = 0.041). The mfERG responses in the region of eccentricity between 1.8° and 7° were significantly higher in treated patients (P = 0.04). Conclusions. RHF contributed to sparing of photoreceptor IS/OS junction integrity in the fovea, which is assumed to be a predictive factor for preservation of visual acuity. PMID:26351571

  14. 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

  15. Enhanced visualization of acute macular neuroretinopathy by Heidelberg Retina Tomography.

    PubMed

    Mirshahi, Alireza; Scharioth, Gàbor B; Klais, Christina M C; Baatz, Holger

    2006-08-01

    We report Heidelberg Retina Tomography (HRT) findings in a case of bilateral acute macular neuroretinopathy in a 22-year-old man. In addition to fundus photography, fluorescein and indocyanine green angiography, and visual field testing, HRT scans of the macula were performed early in the disease and at a follow up of 2 months. We found typical paracentral scotomata in visual field testing corresponding to sharply delineated, hyporeflective areas of the macula as visualized in HRT II scans. Those lesions were almost invisible on regular fundus photographs. Angiography results were unremarkable. The lesion size decreased over time. The visibility of the lesions was markedly enhanced by HRT scans, thus the diagnosis and follow up of acute macular neuroretinopathy could be facilitated by this non-invasive imaging technique. PMID:16925709

  16. MACULAR COLOBOMA IN A CHILD WITH USHER SYNDROME.

    PubMed

    Ishaq, Mazhar; Mukhtar, Ahsan; Khan, Saim

    2015-01-01

    Macular coloboma is a rare entity and its concomitance with Usher syndrome is described here. A 14 years male child was studied in detail along with other family members. He underwent two complete ophthalmologic examinations (4-years follow-up), including visual assessment, orthoptic evaluation, colour vision test, visual fields, corneal topography, Optical coherence tomography, fluorescein angiography, and electroretinography. Detailed ophthalmic examination was also conducted on other asymptomatic members of the same family. Patient had sensorineural deafness, poor visual acuity, and progressive visual field impairment in both eyes, bilaterally presenting macular coloboma and atypical retinitis pigmentosa pattern. The other investigated relatives did not show any specific and/or significant ocular disorder. This concurrence represents no genetic pattern and is observed in sporadic cases. PMID:26411142

  17. Oral and silent reading performance with macular degeneration.

    PubMed

    Lovie-Kitchin, J E; Bowers, A R; Woods, R L

    2000-09-01

    Previous studies have shown that reading rate for very large print (6 degrees, 1.86 logMAR character size) is a strong predictor of oral reading rate with low vision devices (LVDs). We investigated whether this would apply using large print sizes more readily available in clinical situations (e.g. 2 degrees, 1.4 logMAR), for subjects with macular degeneration. We assessed rauding rates--reading for understanding. A combination of near word visual acuity and large print reading rate (without LVDs) provided the best prediction of oral rauding rates (with LVDs). However, near word visual acuity alone was almost as good. Similarly, silent rauding rate was predicted best by near word visual acuity alone. We give near visual acuity limits as a clinical guide to expected oral and silent reading performance with LVDs for patients with macular degeneration. PMID:11045244

  18. The problem of macular sparing after unilateral occipital lesions.

    PubMed

    Sugishita, M; Hemmi, I; Sakuma, I; Beppu, H; Shiokawa, Y

    1993-11-01

    Whether or not unilateral occipital damage produces sparing of central vision, namely macular sparing, is controversial. We tested two subjects with left occipital lesions by means of fundus perimetry combined with fundus image analysis. This method made it possible to measure the distance of the stimulus projected on the retina from the foveal centre defined as the centre of the foveal reflex. The results indicated that macular sparing, if it exists, must be less than 0.4 degree wide. Two of the four eyes during the stimulus presentation often but not always showed eccentric fixation of a small magnitude, whose mean was less than 0.6 degree from the foveal centre in the right hemiretina. PMID:8138815

  19. Surgical treatment of retinal detachment owing to macular hole.

    PubMed

    Wolfensberger, T J; Gonvers, M

    2000-06-01

    Retinal detachments owing to macular hole have a low prevalence and occur predominantly in myopic eyes. The choice of surgical technique is primarily based on the axial length of the globe and on the presence or absence of a posterior staphyloma and/or chorioretinal degenerations. Whereas patients with low myopia and no posterior staphyloma are best treated with primary pars plana vitrectomy and air tamponade, patients with marked myopia and large posterior staphylomas should be managed by combining a pars plana vitrectomy with laser photocoagulation of the macular hole rim under perfluorocarbon liquids and a temporary silicone oil tamponade. For the intermediate myopias the surgical technique has to be decided from patient to patient. PMID:11309744

  20. 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.

  1. Social stress effects on pigmentation and monoamines in Arctic charr.

    PubMed

    Backstrm, Tobias; Heynen, Martina; Brnns, 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. PMID:25997582

  2. Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail.

    PubMed

    Kim, Joo-Hyun; Park, Seoyoung; Chung, Hyewon; Oh, Sangtaek

    2015-09-01

    Activation of the Wnt/β-catenin pathway plays a pathogenic role in age-related macular degeneration (AMD) and is thus a potential target for the development of therapeutics for this disease. Here, we demonstrated that Wnt5a antagonized β-catenin response transcription (CRT) induced with Wnt3a by promoting β-catenin phosphorylation at Ser33/Ser37/Thr41 and its subsequent degradation in human retinal pigment epithelial (RPE) cells. Wnt5a decreased the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB), which was up-regulated by Wnt3a. Furthermore, Wnt5a increased E-cadherin expression and decreased cell migration by down-regulating Snail expression, thereby abrogating the Wnt3a-induced epithelial-mesenchymal transition (EMT) in human RPE cells. Our findings suggest that Wnt5a suppresses the pathogenic effects of canonical Wnt signaling in human RPE cells by promoting β-catenin phosphorylation and degradation. Therefore, Wnt5a has significant therapeutic potential for the treatment of AMD. PMID:26246285

  3. 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

  4. Inverted Internal Limiting Membrane Flap For Large Traumatic Macular Holes.

    PubMed

    Abou Shousha, Mohsen Ahmed

    2016-01-01

    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

  5. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; Garca-Medina, Jos Javier; Garca-Layana, Alfredo; Pons-Vzquez, Sheila; Pinazo-Durn, M. Dolores; Gmez-Ulla, Francisco; Arvalo, J. Fernando; Daz-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

  6. 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

  7. Independence and interdependence of the photoregulation of pigmentation and development in Fremyella diplosiphon.

    PubMed

    Bordowitz, Juliana R; Whitaker, Melissa J; Montgomery, Beronda L

    2010-03-01

    Many photosynthetic organisms exhibit light-dependent regulation of growth and development, including photoregulation of pigmentation, physiology, and form. We recently demonstrated that the photoregulation of cellular and filament morphology in Fremyella diplosiphon is under control of a photosensory photoreceptor and differentially impacted by photosynthetic pigment accumulation. Biliprotein photoreceptor RcaE controls the light-dependent regulation of pigmentation and of cell and filament morphology in F. diplosiphon, primarily in response to green and red light as a part of a light acclimation process known as complementary chromatic adaptation (CCA). Our recent investigations into the regulation of CCA underscored the largely independent regulation of pigmentation and cell shape by RcaE. However, recent studies on the regulation of phycobiliprotein biosynthesis indicated that filament length may depend upon correct photoregulation of photosynthetic pigment levels. Taken together, these studies suggest that aspects of the regulation of morphology in F. diplosiphon are independent of the regulation of pigmentation, yet other features of morphology depend upon the accurate photoregulation of pigment levels. PMID:20585508

  8. 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 urine when given intravenously. Contrasting with blood hemoglobin this musde hemoglobin under identical conditions does not cause the deposit of iron staining pigment within the epithelium of the renal tubules. A pigment giving no iron staining reaction may be found in the epithelium of the convoluted tubules of the kidney. Whether this is due to dietary or other factors is uncertain but this indicates pigment conservation by the kidney. Finally we would emphasize again the fact that the kidney is of considerable importance in the conservation of hemoglobin and hemoglobin split products which presumably are utilized to build up new hemoglobin. PMID:19870019

  9. Retinal layer segmentation of macular OCT images using boundary classification

    PubMed Central

    Lang, Andrew; Carass, Aaron; Hauser, Matthew; Sotirchos, Elias S.; Calabresi, Peter A.; Ying, Howard S.; Prince, Jerry L.

    2013-01-01

    Optical coherence tomography (OCT) has proven to be an essential imaging modality for ophthalmology and is proving to be very important in neurology. OCT enables high resolution imaging of the retina, both at the optic nerve head and the macula. Macular retinal layer thicknesses provide useful diagnostic information and have been shown to correlate well with measures of disease severity in several diseases. Since manual segmentation of these layers is time consuming and prone to bias, automatic segmentation methods are critical for full utilization of this technology. In this work, we build a random forest classifier to segment eight retinal layers in macular cube images acquired by OCT. The random forest classifier learns the boundary pixels between layers, producing an accurate probability map for each boundary, which is then processed to finalize the boundaries. Using this algorithm, we can accurately segment the entire retina contained in the macular cube to an accuracy of at least 4.3 microns for any of the nine boundaries. Experiments were carried out on both healthy and multiple sclerosis subjects, with no difference in the accuracy of our algorithm found between the groups. PMID:23847738

  10. Polarized Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cell Monolayers Have Higher Resistance to Oxidative Stress-Induced Cell Death Than Nonpolarized Cultures

    PubMed Central

    Hsiung, Jamie; Zhu, Danhong

    2015-01-01

    Oxidative stress-mediated injury to the retinal pigment epithelium (RPE) is a major factor involved in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. Human embryonic stem cell (hESC)-derived RPE cells are currently being evaluated for their potential for cell therapy in AMD patients through subretinal injection of cells in suspension and subretinal placement as a polarized monolayer. To gain an understanding of how transplanted RPE cells will respond to the highly oxidatively stressed environment of an AMD patient eye, we compared the survival of polarized and nonpolarized RPE cultures following oxidative stress treatment. Polarized, nonpolarized/confluent, nonpolarized/subconfluent hESC-RPE cells were treated with H2O2. Terminal deoxynucleotidyl transferase dUTP nick end labeling stains revealed the highest amount of cell death in subconfluent hESC-RPE cells and little cell death in polarized hESC-RPE cells with H2O2 treatment. There were higher levels of proapoptotic factors (phosphorylated p38, phosphorylated c-Jun NH2-terminal kinase, Bax, and cleaved caspase 3 fragments) in treated nonpolarized RPE—particularly subconfluent cells—relative to polarized cells. On the other hand, polarized RPE cells had constitutively higher levels of cell survival and antiapoptotic signaling factors such as p-Akt and Bcl-2, as well as antioxidants superoxide dismutase 1 and catalase relative to nonpolarized cells, that possibly contributed to polarized cells’ higher tolerance to oxidative stress compared with nonpolarized RPE cells. Subconfluent cells were particularly sensitive to oxidative stress-induced apoptosis. These results suggest that implantation of polarized hESC-RPE monolayers for treating AMD patients with geographic atrophy should have better survival than injections of hESC-RPE cells in suspension. PMID:25411476

  11. The new paradigm: retinal pigment epithelium cells generated from embryonic or induced pluripotent stem cells

    PubMed Central

    Bharti, Kapil; Miller, Sheldon S.; Arnheiter, Heinz

    2010-01-01

    Summary Compared with neural crest-derived melanocytes, retinal pigment epithelium (RPE) cells in the back of the eye are pigment cells of a different kind. They are a part of the brain, form an epithelial monolayer, respond to distinct extracellular signals, and provide functions that far exceed those of a light-absorbing screen. For instance, they control nutrient and metabolite flow to and from the retina, replenish 11-cis-retinal by re-isomerizing all-trans-retinal generated during photoconversion, phagocytose daily a portion of the photoreceptors outer segments, and secrete cytokines that locally control the innate and adaptive immune systems. Not surprisingly, RPE cell damage is a major cause of human blindness worldwide, with age-related macular degeneration a prevalent example. RPE replacement therapies using RPE cells generated from embryonic or induced pluripotent stem cells provide a novel approach to a rational treatment of such forms of blindness. In fact, RPE-like cells can be obtained relatively easily when stem cells are subjected to a two-step induction protocol, a first step that leads to a neuroectodermal fate and a second to RPE differentiation. Here, we discuss the characteristics of such cells, propose criteria they should fulfill in order to be considered authentic RPE cells, and point out the challenges one faces when using such cells in attempts to restore vision. PMID:20846177

  12. Direct conversion of human fibroblasts into retinal pigment epithelium-like cells by defined factors.

    PubMed

    Zhang, Kejing; Liu, Guang-Hui; Yi, Fei; Montserrat, Nuria; Hishida, Tomoaki; Esteban, Concepcion Rodriguez; Izpisua Belmonte, Juan Carlos

    2014-01-01

    The generation of functional retinal pigment epithelium (RPE) is of great therapeutic interest to the field of regenerative medicine and may provide possible cures for retinal degenerative diseases, including age-related macular degeneration (AMD). Although RPE cells can be produced from either embryonic stem cells or induced pluripotent stem cells, direct cell reprogramming driven by lineage-determining transcription factors provides an immediate route to their generation. By monitoring a human RPE specific Best1::GFP reporter, we report the conversion of human fibroblasts into RPE lineage using defined sets of transcription factors. We found that Best1::GFP positive cells formed colonies and exhibited morphological and molecular features of early stage RPE cells. Moreover, they were able to obtain pigmentation upon activation of Retinoic acid (RA) and Sonic Hedgehog (SHH) signaling pathways. Our study not only established an ideal platform to investigate the transcriptional network regulating the RPE cell fate determination, but also provided an alternative strategy to generate functional RPE cells that complement the use of pluripotent stem cells for disease modeling, drug screening, and cell therapy of retinal degeneration. PMID:24474194

  13. Porous Poly(ε-Caprolactone) Scaffolds for Retinal Pigment Epithelium Transplantation

    PubMed Central

    McHugh, Kevin J.; Tao, Sarah L.; Saint-Geniez, Magali

    2014-01-01

    Purpose. Retinal pigment epithelium (RPE) transplantation is a promising strategy for the treatment of dry age-related macular degeneration (AMD). However, previous attempts at subretinal RPE cell transplantation have experienced limited success due to poor adhesion, organization, and function on aged or diseased Bruch's membrane. Instead, cell-based strategies may benefit from a synthetic scaffold that mimics the functions of healthy Bruch's membrane to promote the formation of a functional RPE monolayer while maintaining metabolite exchange between the vasculature and outer retina. Methods. This study evaluated the behavior of human RPE on nanopatterned porous poly(ε-caprolactone) (PCL) film as a potential scaffold for therapeutic transplantation. Fetal human RPE (fhRPE) was cultured on porous PCL, nonporous PCL, or Costar porous polyester transwells for up to 8 weeks and assessed using light microscopy, fluorescent microscopy, transepithelial resistance, quantitative PCR, ELISAs, and phagocytosis assays. Results. fhRPE on porous PCL displayed improved markers of maturity and function compared with both porous polyester transwells and nonporous PCL, including pigmentation, increased cell density, superior barrier function, up-regulation of RPE-specific genes, and polarized growth factor secretion. Conclusions. This study indicates that porous PCL is an attractive scaffold for RPE transplantation. In addition to being biocompatible with the subretinal space, porous PCL also allows for trans-scaffold metabolite transport and significantly improves RPE cell behavior compared to nonporous PCL or porous polyester transwells. PMID:24550370

  14. Development of gene therapy for treatment of age-related macular degeneration.

    PubMed

    Askou, Anne Louise

    2014-07-01

    Intraocular neovascular diseases are the leading cause of blindness in the Western world in individuals over the age of 50. Age-related macular degeneration (AMD) is one of these diseases. Exudative AMD, the late-stage form, is characterized by abnormal neovessel development, sprouting from the choroid into the avascular subretinal space, where it can suddenly cause irreversible damage to the vulnerable photoreceptor (PR) cells essential for our high-resolution, central vision. The molecular basis of AMD is not well understood, but several growth factors have been implicated including vascular endothelial growth factor (VEGF), and the advent of anti-VEGF therapy has markedly changed the outcome of treatment. However, common to all current therapies for exudative AMD are the complications of repeated monthly intravitreal injections, which must be continued throughout one's lifetime to maintain visual benefits. Additionally, some patients do not benefit from established treatments. Strategies providing long-term suppression of inappropriate ocular angiogenesis are therefore needed, and gene therapy offers a potential powerful technique. This study aimed to develop a strategy based on RNA interference (RNAi) for the sustained attenuation of VEGF. We designed a panel of anti-VEGF short hairpin RNAs (shRNA), and based on the most potent shRNAs, microRNA (miRNA)-mimicked hairpins were developed. We demonstrated an additive VEGF silencing effect when we combined the miRNAs in a tricistronic miRNA cluster. To meet the requirements for development of medical treatments for AMD with long-term effects, the shRNA/miRNA is expressed from vectors based on adeno-associated virus (AAV) or lentivirus (LV). Both vector systems have been found superior in terms of transduction efficiency and persistence in gene expression in retinal cells. The capacity of AAV-encoded RNAi effector molecules to silence endogenous VEGF gene expression was evaluated in mouse models, including the model 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. PMID:24953666

  15. 5'-Adenosine monophosphate-activated protein kinase--mammalian target of rapamycin axis as therapeutic target for age-related macular degeneration.

    PubMed

    Hyttinen, Juha M T; Petrovski, Goran; Salminen, Antero; Kaarniranta, Kai

    2011-12-01

    Age-related macular degeneration (AMD) is the most common reason for blindness in developed countries. AMD essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells, and extracellular drusen formation, as well as presence of chronic inflammation in the retina. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells, which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. The formation of lipofuscin, in turn, decreases the lysosomal enzyme activity and impairs the autophagic clearance of damaged proteins destined for cellular removal. 5'-Adenosine monophosphate-activated protein kinase (AMPK) is a well-known inhibitor of mammalian target of rapamycin (mTOR) that subsequently evokes induction of autophagy. This review examines the novel potential therapeutic targets on the AMPK-mTOR axis and the ways in which autophagy clearance can suppress or prevent RPE degeneration and development of AMD. PMID:22007913

  16. Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images

    PubMed Central

    Srinivasan, Pratul P.; Kim, Leo A.; Mettu, Priyatham S.; Cousins, Scott W.; Comer, Grant M.; Izatt, Joseph A.; Farsiu, Sina

    2014-01-01

    We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases. PMID:25360373

  17. 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. PMID:24783946

  18. 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)

  19. Nanoscale porosity in pigments for chemical sensing

    PubMed Central

    Kemling, Jonathan W.; Suslick, Kenneth S.

    2012-01-01

    Porous pigments in which chemically responsive dyes have been immobilized in a matrix of organically modified siloxanes (ormosils) have been prepared and characterized by AFM, TEM, EDS, and optical analysis. In typical chemical sensing applications, an array of 36 different porous ormosil pigments are deposited on polyethylene terephthalate (PET) film. PMID:21423939

  20. Endocrine factors as effectors of integumental pigmentation.

    PubMed

    Abdel-Malek, Z A

    1988-04-01

    Normal and malignant pigment cells are known targets for many hormones. Besides alpha-melanocyte-stimulating hormone and the steroidal hormones estrogen, testosterone, and glucocorticoids, factors produced by other epidermal cells can affect melanization and proliferation of pigment cells. Among those factors are the prostaglandins, vitamin D3, ETAF, and interleukin-1. PMID:3132340

  1. [Pigmented lesions of the oral cavity].

    PubMed

    Brocheriou, C; Kuffer, R; Verola, O

    1985-01-01

    Pigmented lesions of the oral cavity are of multiple origin. They can be subdivided as follows: non tumoral pigmentations, non melanin pigmented tumors or tumor-like lesions, benign melanin pigmented tumors and malignant melanomas. Among non tumoral pigmented lesions, some of them show melanin deposits: they can be associated with a systemic disease (Peutz Jeghers syndrome, Addison's disease) or have a medicamentous origin, or belong to a lichen migricans. Non tumoral and non melanin pigmentations are principally due to a heavy metal accumulation or an accidental tatoo arising after tooth treatment. Peripheral giant cell granuloma, so-called giant cell epulis is the major non pigmented non melanin pseudotumoral lesion; pigmentation is due to hemosiderin deposits. In the oral cavity nevi are principally of the intramucosal type. Blue nevus, the second type in frequency, is usually located on the hard palate. Primary malignant melanomas are rare in the oral cavity, but it is--because its very bad prognosis--the most important lesion. In order to improve the survival it is necessary to do the diagnosis as early as possible. PMID:3833244

  2. ORGANIC DYES AND PIGMENTS DATA BASE

    EPA Science Inventory

    The objective of this research program was to compile a data base covering all the commercially significant dyes and pigments produced or imported in the United States. The Organic Dyes and Pigments Data Base (ODPDB) contains the following data elements: chemical-related data (co...

  3. 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

  4. Quantitative Proteomics: Comparison of the Macular Bruch Membrane/Choroid Complex from Age-related Macular Degeneration and Normal Eyes*

    PubMed Central

    Yuan, Xianglin; Gu, Xiaorong; Crabb, John S.; Yue, Xiuzhen; Shadrach, Karen; Hollyfield, Joe G.; Crabb, John W.

    2010-01-01

    A quantitative proteomics analysis of the macular Bruch membrane/choroid complex was pursued for insights into the molecular mechanisms of age-related macular degeneration (AMD). Protein in trephine samples from the macular region of 10 early/mid-stage dry AMD, six advanced dry AMD, eight wet AMD, and 25 normal control post-mortem eyes was analyzed by LC MS/MS iTRAQ (isobaric tags for relative and absolute quantitation) technology. A total of 901 proteins was quantified, including 556 proteins from ≥3 AMD samples. Most proteins differed little in amount between AMD and control samples and therefore reflect the proteome of normal macular tissues of average age 81. A total of 56 proteins were found to be elevated and 43 were found to be reduced in AMD tissues relative to controls. Analysis by category of disease progression revealed up to 16 proteins elevated or decreased in each category. About 60% of the elevated proteins are involved in immune response and host defense, including many complement proteins and damage-associated molecular pattern proteins such as α-defensins 1–3, protein S100s, crystallins, histones, and galectin-3. Four retinoid processing proteins were elevated only in early/mid-stage AMD, supporting a role for retinoids in AMD initiation. Proteins uniquely decreased in early/mid-stage AMD implicate hematologic malfunctions and weakened extracellular matrix integrity and cellular interactions. Galectin-3, a receptor for advanced glycation end products, was the most significantly elevated protein in advanced dry AMD, supporting a role for advanced glycation end products in dry AMD progression. The results endorse inflammatory processes in both early and advanced AMD pathology, implicate different pathways of progression to advanced dry and wet AMD, and provide a new database for hypothesis-driven and discovery-based studies of AMD. PMID:20177130

  5. Genetic Analysis of Pigmentation in Cordyceps militaris

    PubMed Central

    Shrestha, Bhushan; Choi, Sung-Keun; Kim, Ho-Kyoung; Kim, Tae-Woong

    2005-01-01

    Pigmentation of ascospore-derived isolates from seven different natural specimens of Cordyceps militaris EFCC C-5888, EFCC C-7159, EFCC C-7833, EFCC C-7991, EFCC C-8021, EFCC C-8023 and EFCC C-8179 was observed on the plates of Sabouraud Dextrose agar plus Yeast Extract at 25℃ under continuous illumination (500 lux). Pigmentation of the wild-type isolates of C. militaris was diverse ranging from yellowish white to orange, while white color was believed as a mutant. Inheritance of pigmentation was found to be controlled by both parental isolates when F1 progeny were analyzed. Pigmentation and mating type were shown to be either independent or distantly linked each other due to the high percentage of non-parental phenotypes among F1 progeny. Crosses between white mutant isolates of C. militaris yielded progeny with wild type pigmentations, indicating that the albino mutations in the parents were unlinked to each other. PMID:24049487

  6. Comparison and interchangeability of macular thickness measured with Cirrus OCT and Stratus OCT in myopic eyes

    PubMed Central

    Wang, Geng; Qiu, Kun-Liang; Lu, Xue-Hui; Zhang, Ming-Zhi

    2015-01-01

    AIM To investigate the difference of macular thickness measurements between stratus optical coherence tomography (OCT) and Cirrus OCT (Carl Zeiss Meditec, Dublin, CA, USA) in the same myopic patient and to develop a conversion equation to interchange macular thickness obtained with these two OCT devices. METHODS Eighty-nine healthy Chinese adults with spherical equivalent (SE) ranging from -1.13 D to -9.63 D were recruited. The macular thickness was measured by Cirrus OCT and Stratus OCT. The correlation between macular thickness and axial length and the agreement between two OCT measurements were evaluated. A formula was generated to interchange macular thickness obtained with two OCT devices. RESULTS Average macular thickness measured with Stratus OCT (r=-0.280, P=0.008) and Cirrus OCT (r=-0.224, P=0.034) were found to be negatively correlated with axial length. No statistically significant correlation was found between axial length and central subfield macular thickness (CMT) measured with Stratus OCT (r=0.191, P=0.073) and Cirrus OCT (r=0.169, P=0.113). The mean CMT measured with Cirrus OCT was 53.63±7.94 µm thicker than with Stratus OCT. The formula CMTCirrus OCT=78.328+0.874×CMTStratus OCT was generated to interchange macular thickness obtained with two OCT devices. CONCLUSION Macular thickness measured with Cirrus OCT were thicker than with Stratus OCT in myopic eyes. A formula can be used to interchange macular thickness measured with two OCT devices in myopic eyes. Studies with different OCT devices and larger samples are warranted to enable the comparison of macular values measured with different OCT devices. PMID:26682172

  7. Retro-Mode Scanning Laser Ophthalmoscopy Planning for Navigated Macular Laser Photocoagulation in Macular Edema

    PubMed Central

    Boiko, Ernest V.; Maltsev, Dmitrii S.

    2016-01-01

    Purpose. To compare treatment areas and navigated macular laser photocoagulation (MLP) plans suggested by retro-mode scanning laser ophthalmoscopy (RM-SLO) image versus optical coherence tomography (OCT) central retinal thickness map and treatment planning among retina specialists. Methods. Thirty-nine eyes with diabetic or branch retinal vein occlusion-related ME undergoing navigated MLP with navigated photocoagulator had OCT and RM-SLO taken. OCT map and RM-SLO image were imported to the photocoagulator and aligned onto the retina. Two retina specialists placed laser spot marks separately based on OCT and RM-SLO images in a random fashion. The spots placed by each physician were compared between OCT and RM-SLO and among physicians. The areas of retinal edema on OCT and RM-SLO of the same eye were also compared. Results. The average number of laser spots using RM-SLO and OCT template was 189.6 ± 77.4 and 136.6 ± 46.8, respectively, P = 0.003. The average area of edema on RM-SLO image was larger than that on OCT map (14.5 ± 3.9 mm2 versus 10.3 ± 2.8 mm2, P = 0.005) because of a larger scanning area. There was narrow variability in treatment planning among retina specialists for both RM-SLO (P = 0.13) and OCT (P = 0.19). Conclusion. The RM-SLO image superimposed onto the fundus of the same eye can be used to guide MLP with narrow variability in treatment planning among retina specialists. The treatment areas suggested by RM-SLO-guided MLP plans for ME were shown to be larger than those suggested by OCT-guided plans. PMID:26989498

  8. Retro-Mode Scanning Laser Ophthalmoscopy Planning for Navigated Macular Laser Photocoagulation in Macular Edema.

    PubMed

    Boiko, Ernest V; Maltsev, Dmitrii S

    2016-01-01

    Purpose. To compare treatment areas and navigated macular laser photocoagulation (MLP) plans suggested by retro-mode scanning laser ophthalmoscopy (RM-SLO) image versus optical coherence tomography (OCT) central retinal thickness map and treatment planning among retina specialists. Methods. Thirty-nine eyes with diabetic or branch retinal vein occlusion-related ME undergoing navigated MLP with navigated photocoagulator had OCT and RM-SLO taken. OCT map and RM-SLO image were imported to the photocoagulator and aligned onto the retina. Two retina specialists placed laser spot marks separately based on OCT and RM-SLO images in a random fashion. The spots placed by each physician were compared between OCT and RM-SLO and among physicians. The areas of retinal edema on OCT and RM-SLO of the same eye were also compared. Results. The average number of laser spots using RM-SLO and OCT template was 189.6 ± 77.4 and 136.6 ± 46.8, respectively, P = 0.003. The average area of edema on RM-SLO image was larger than that on OCT map (14.5 ± 3.9 mm(2) versus 10.3 ± 2.8 mm(2), P = 0.005) because of a larger scanning area. There was narrow variability in treatment planning among retina specialists for both RM-SLO (P = 0.13) and OCT (P = 0.19). Conclusion. The RM-SLO image superimposed onto the fundus of the same eye can be used to guide MLP with narrow variability in treatment planning among retina specialists. The treatment areas suggested by RM-SLO-guided MLP plans for ME were shown to be larger than those suggested by OCT-guided plans. PMID:26989498

  9. Primary structures of chicken cone visual pigments: vertebrate rhodopsins have evolved out of cone visual pigments.

    PubMed Central

    Okano, T; Kojima, D; Fukada, Y; Shichida, Y; Yoshizawa, T

    1992-01-01

    The chicken retina contains rhodopsin (a rod visual pigment) and four kinds of cone visual pigments. The primary structures of chicken red (iodopsin) and rhodopsin have been determined previously. Here we report isolation of three cDNA clones encoding additional pigments from a chicken retinal cDNA library. Based on the partial amino acid sequences of the purified chicken visual pigments together with their biochemical and spectral properties, we have identified these clones as encoding the chicken green, blue, and violet visual pigments. Chicken violet was very similar to human blue not only in absorption maximum (chicken violet, 415 nm; human blue, 419 nm) but also in amino acid sequence (80.6% identical). Interestingly, chicken green was more similar (71-75.1%) than any other known cone pigment (42.0-53.7%) to vertebrate rhodopsins. The fourth additional cone pigment, chicken blue, had relatively low similarity (39.3-54.6%) in amino acid sequence to those of the other vertebrate visual pigments. A phylogenetic tree of vertebrate visual pigments constructed on the basis of amino acid identity indicated that an ancestral visual pigment evolved first into four groups (groups L, S, M1, and M2), each of which includes one of the chicken cone pigments, and that group Rh including vertebrate rhodopsins diverged from group M2 later. Thus, it is suggested that the gene for scotopic vision (rhodopsin) has evolved out of that for photopic vision (cone pigments). The divergence of rhodopsin from cone pigments was accompanied by an increase in negative net charge of the pigment. Images PMID:1385866

  10. Pigment epithelium-derived factor reduces apoptosis and pro-inflammatory cytokine gene expression in a murine model of focal retinal degeneration

    PubMed Central

    Wang, Yujuan; Subramanian, Preeti; Shen, Defen; Tuo, Jingsheng; Becerra, S. Patricia; Chan, Chi-Chao

    2013-01-01

    AMD (age-related macular degeneration) is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor) is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2−/−/Cx3cr1−/− on C57BL/6N [Crb1rd8]) mice, a model for progressive, focal rd (retinal degeneration). First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium) than WT (wild-type, C57BL/6N). Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg), followed by a subconjunctival injection of PEDF (3 μg) 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment. PMID:24160756

  11. 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).

  12. Anthocyanins. Plant pigments and beyond.

    PubMed

    Santos-Buelga, Celestino; Mateus, Nuno; De Freitas, Victor

    2014-07-23

    Anthocyanins are plant pigments widespread in nature. They play relevant roles in plant propagation and ecophysiology and plant defense mechanisms and are responsible for the color of fruits and vegetables. A large number of novel anthocyanin structures have been identified, including new families such as pyranoanthocyanins or anthocyanin oligomers; their biosynthesis pathways have been elucidated, and new plants with "a la carte" colors have been created by genetic engineering. Furthermore, evidence about their benefits in human health has accumulated, and processes of anthocyanin absorption and biotransformation in the human organism have started to be ascertained. These advances in anthocyanin research were revised in the Seventh International Workshop on Anthocyanins that took place in Porto (Portugal) on September 9-11, 2013. Some selected papers are collected in this special issue, where aspects such as anthocyanin accumulation in plants, relationship with color expression, stability in plants and food, and bioavailability or biological activity are revised. PMID:24970106

  13. Human pigmentation variation: evolution, genetic basis, and implications for public health.

    PubMed

    Parra, Esteban J

    2007-01-01

    Pigmentation, which is primarily determined by the amount, the type, and the distribution of melanin, shows a remarkable diversity in human populations, and in this sense, it is an atypical trait. Numerous genetic studies have indicated that the average proportion of genetic variation due to differences among major continental groups is just 10-15% of the total genetic variation. In contrast, skin pigmentation shows large differences among continental populations. The reasons for this discrepancy can be traced back primarily to the strong influence of natural selection, which has shaped the distribution of pigmentation according to a latitudinal gradient. Research during the last 5 years has substantially increased our understanding of the genes involved in normal pigmentation variation in human populations. At least six genes have been identified using genotype/phenotype association studies and/or direct functional assays, and there is evidence indicating that several additional genes may be playing a role in skin, hair, and iris pigmentation. The information that is emerging from recent studies points to a complex picture where positive selection has been acting at different genomic locations, and for some genes only in certain population groups. There are several reasons why elucidating the genetics and evolutionary history of pigmentation is important. 1) Pigmentation is a trait that should be used as an example of how misleading simplistic interpretations of human variation can be. It is erroneous to extrapolate the patterns of variation observed in superficial traits such as pigmentation to the rest of the genome. It is similarly misleading to suggest, based on the "average" genomic picture, that variation among human populations is irrelevant. The study of the genes underlying human pigmentation diversity brings to the forefront the mosaic nature of human genetic variation: our genome is composed of a myriad of segments with different patterns of variation and evolutionary histories. 2) Pigmentation can be very useful to understand the genetic architecture of complex traits. The pigmentation of unexposed areas of the skin (constitutive pigmentation) is relatively unaffected by environmental influences during an individual's lifetime when compared with other complex traits such as diabetes or blood pressure, and this provides a unique opportunity to study gene-gene interactions without the effect of environmental confounders. 3) Pigmentation is of relevance from a public health perspective, because of its critical role in photoprotection and vitamin D synthesis. Fair-skinned individuals are at higher risk of several types of skin cancer, particularly in regions with high UVR incidence, and dark-skinned individuals living in high latitude regions are at higher risk for diseases caused by deficient or insufficient vitamin D levels. PMID:18046745

  14. 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.

  15. 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

  16. Subducted and Melanotic Cells in Advanced Age-Related Macular Degeneration Are Derived From Retinal Pigment Epithelium

    PubMed Central

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

    2015-01-01

    Purpose. To describe, illustrate, and account for two cell types plausibly derived from RPE in geographic atrophy (GA) and choroidal neovascularization (CNV) of AMD, using melanosomes, lipofuscin, and basal laminar deposit (BLamD) as anatomical markers. Methods. Human donor eyes with GA (n = 13) or CNV (n = 39) were histologically processed, photodocumented, and analyzed for frequencies of occurrence. We defined RPE as cells containing spindle-shaped melanosomes and RPE lipofuscin, internal to basal lamina or BLamD, if present, or Bruch's membrane if not, and RPE-derived cells as those plausibly derived from RPE and not attached to basal lamina or BLamD. Results. ‘Subducted’ cells contain RPE melanosomes and localize to the sub-RPE space, on Bruch's membrane. Credible transitional forms from RPE cells were seen. Grades of RPE overlying ‘Subducted’ cells were ‘Atrophic with BLamD’ (32.2% vs. 37.0% of ‘Subducted,’ for GA and CNV eyes, respectively), ‘Dissociated’ (22.0% vs. 21.7%), ‘Nonuniform’ (22.0% vs. 23.9%), and ‘Sloughed’ RPE (10.2% vs. 4.3%). Found exclusively in CNV scars, ‘Melanotic’ cells containing spherical melanosomes were adjacent to ‘Entombed’ RPE with spindle-shaped and spherical melanosomes. Of subretinal ‘Melanotic’ cells, 40.0% associated with ‘Atrophy with BLamD,’ 36.8% with ‘Atrophy without BLamD,’ and 20.6% with ‘Entombed.’ Conclusions. ‘Dissociated’ RPE within atrophic areas may be the source of ‘Subducted’ cells. ‘Entombed’ RPE within fibrovascular and fibrocellular scars may be the source of ‘Melanotic’ cells. An imaging correlate for ‘Subducted’ cells awaits discovery; ‘Melanotic’ cells appear gray-black in the CNV fundus. Results provide a basis for future molecular phenotyping studies. PMID:26024109

  17. Analyzing OCT images of age-related macular degeneration patients to identify spatial health correlations.

    PubMed

    Go, Susannah; Chundi, Parvathi; Subramaniam, Mahadevan; Margalit, Eyal

    2015-08-01

    An approach to automatically group age-related macular degeneration (AMD) patients having similar retinal health profiles by clustering Optical Coherence Tomography (OCT) images is described. Spatial health patterns within and across profiles are discovered by identifying segments of images that have similar levels of health in a given retina region. Segmentations of various sizes are considered and the segmentation where the segment similarity most closely matches the discovered health profiles is used to identify health patterns. Our experiments with OCT images of 10 AMD patients show that - i) health profiles generated by clustering closely correspond to those identified by a physician expert, ii) a rich set of spatial patterns can be discovered within and across profiles using regular image segmentation, and iii) new images can be successfully classified into existing profiles so that physicians can provide effective profile-based treatments. PMID:26738180

  18. Measurement of retinal thickness in macular region of high myopic eyes using spectral domain OCT

    PubMed Central

    Song, Ai-Ping; Wu, Xin-Yi; Wang, Jian-Rong; Liu, Wei; Sun, Yan; Yu, Tao

    2014-01-01

    AIM To investigate the changes of retinal thickness in macula of high myopic eyes using spectral domain optical coherence tomography (OCT). METHODS Middle-aged and young myopic patients were divided into three groups according to their refractive error/axial length: low and medium myopia group (LMMG), high myopia group (HMG) and super high myopia group (SHMG). Cirrus HD-OCT was used to evaluate total average macular thickness, central subfield thickness, inner/outer macular thickness and macular volume. The differences among experimental groups were analyzed by one-factor analysis of variance. Associations between macular thickness and refractive error/axial length were analyzed by Pearson correlation analysis. RESULTS There was no significant difference in age among the three groups (P=0.2789). The mean refraction error in the LMMG, HMG, and SHMG groups was -2.49±1.38D, -8.53±1.95D and -13.88±1.76D, respectively (P<0.001). The central subfield thickness of three groups was 244.56±12.19µm, 254.33±11.61µm and 261.75±11.83µm, respectively, and there were statistically significance between random two groups. The total average macular thickness, inner/outer macular thickness, and macular volume decreased with increased myopia/axial length. Average foveal thickness had negative correlations with refractive error (P<0.001), and positive correlations with axial length. The inferior and temporal inner macular thickness, all the quadrants of outer ring, total average macular thickness and macular volume featured positive correlations with refractive error, and negative correlations with axial length. Average foveal thickness, superior and temporal inner macular thicknesses, and temporal outer macular thickness was lower in females compared to males. CONCLUSION With an increase in myopia degree/axial length, the average foveal thickness increased and the inner/outer macular thickness decreased. Females featured thicker average foveal thickness, and thinner macular thickness compared to males. PMID:24634877

  19. Efficient delivery and functional expression of transfected modified mRNA in human embryonic stem cell-derived retinal pigmented epithelial cells.

    PubMed

    Hansson, Magnus L; Albert, Silvia; González Somermeyer, Louisa; Peco, Rubén; Mejía-Ramírez, Eva; Montserrat, Núria; Izpisua Belmonte, Juan Carlos

    2015-02-27

    Gene- and cell-based therapies are promising strategies for the treatment of degenerative retinal diseases such as age-related macular degeneration, Stargardt disease, and retinitis pigmentosa. Cellular engineering before transplantation may allow the delivery of cellular factors that can promote functional improvements, such as increased engraftment or survival of transplanted cells. A current challenge in traditional DNA-based vector transfection is to find a delivery system that is both safe and efficient, but using mRNA as an alternative to DNA can circumvent these major roadblocks. In this study, we show that both unmodified and modified mRNA can be delivered to retinal pigmented epithelial (RPE) cells with a high efficiency compared with conventional plasmid delivery systems. On the other hand, administration of unmodified mRNA induced a strong innate immune response that was almost absent when using modified mRNA. Importantly, transfection of mRNA encoding a key regulator of RPE gene expression, microphthalmia-associated transcription factor (MITF), confirmed the functionality of the delivered mRNA. Immunostaining showed that transfection with either type of mRNA led to the expression of roughly equal levels of MITF, primarily localized in the nucleus. Despite these findings, quantitative RT-PCR analyses showed that the activation of the expression of MITF target genes was higher following transfection with modified mRNA compared with unmodified mRNA. Our findings, therefore, show that modified mRNA transfection can be applied to human embryonic stem cell-derived RPE cells and that the method is safe, efficient, and functional. PMID:25555917

  20. Efficient Delivery and Functional Expression of Transfected Modified mRNA in Human Embryonic Stem Cell-derived Retinal Pigmented Epithelial Cells

    PubMed Central

    Hansson, Magnus L.; Albert, Silvia; González Somermeyer, Louisa; Peco, Rubén; Mejía-Ramírez, Eva; Montserrat, Núria; Izpisua Belmonte, Juan Carlos

    2015-01-01

    Gene- and cell-based therapies are promising strategies for the treatment of degenerative retinal diseases such as age-related macular degeneration, Stargardt disease, and retinitis pigmentosa. Cellular engineering before transplantation may allow the delivery of cellular factors that can promote functional improvements, such as increased engraftment or survival of transplanted cells. A current challenge in traditional DNA-based vector transfection is to find a delivery system that is both safe and efficient, but using mRNA as an alternative to DNA can circumvent these major roadblocks. In this study, we show that both unmodified and modified mRNA can be delivered to retinal pigmented epithelial (RPE) cells with a high efficiency compared with conventional plasmid delivery systems. On the other hand, administration of unmodified mRNA induced a strong innate immune response that was almost absent when using modified mRNA. Importantly, transfection of mRNA encoding a key regulator of RPE gene expression, microphthalmia-associated transcription factor (MITF), confirmed the functionality of the delivered mRNA. Immunostaining showed that transfection with either type of mRNA led to the expression of roughly equal levels of MITF, primarily localized in the nucleus. Despite these findings, quantitative RT-PCR analyses showed that the activation of the expression of MITF target genes was higher following transfection with modified mRNA compared with unmodified mRNA. Our findings, therefore, show that modified mRNA transfection can be applied to human embryonic stem cell-derived RPE cells and that the method is safe, efficient, and functional. PMID:25555917

  1. Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization.

    PubMed

    Li, Y; Liu, X; Zhou, T; Kelley, M R; Edwards, P; Gao, H; Qiao, X

    2014-01-01

    The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-κB (NF-κB) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-κB, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE-Bruch׳s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. PMID:24624338

  2. Iron-induced Local Complement Component 3 (C3) Up-regulation via Non-canonical Transforming Growth Factor (TGF)-β Signaling in the Retinal Pigment Epithelium.

    PubMed

    Li, Yafeng; Song, Delu; Song, Ying; Zhao, Liangliang; Wolkow, Natalie; Tobias, John W; Song, Wenchao; Dunaief, Joshua L

    2015-05-01

    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 C3d deposits. Humans with aceruloplasminemia causing RPE iron overload had increased RPE C3d deposition. The molecular events in the iron-C3 pathway represent therapeutic targets for AMD or other diseases exacerbated by iron-induced local complement dysregulation. PMID:25802332

  3. Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization

    PubMed Central

    Li, Y.; Liu, X.; Zhou, T.; Kelley, M.R.; Edwards, P.; Gao, H.; Qiao, X.

    2014-01-01

    The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-?B (NF-?B) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-?B, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPEBruch?s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. PMID:24624338

  4. Epigalloccatechin-3-gallate inhibits ocular neovascularization and vascular permeability in human retinal pigment epithelial and human retinal microvascular endothelial cells via suppression of MMP-9 and VEGF activation.

    PubMed

    Lee, Hak Sung; Jun, Jae-Hyun; Jung, Eun-Ha; Koo, Bon Am; Kim, Yeong Shik

    2014-01-01

    Epigalloccatechin-3-gallate (EGCG) is the main polyphenol component of green tea (leaves of Camellia sinensis). EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a key role in the processes of extracellular matrix (ECM) remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor alpha (TNF-α) in human retinal pigment epithelial cells (HRPECs). EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2) by inhibiting generation of reactive oxygen species (ROS). EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs). Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31) on corneal neovascularization (CNV) induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization. PMID:25123184

  5. Surgical Management of Iatrogenic Pigment Dispersion Glaucoma

    PubMed Central

    Mierlo, Camille Van; Pinto, Luis Abegão

    2015-01-01

    ABSTRACT Introduction: Iatrogenic pigment dispersion syndrome generally originates from a repetitive, mechanical trauma to the pigmented posterior epithelium of the iris. This trauma can arise after intraocular surgery, most commonly due to an abnormal contact between the intraocular lens (IOL) and the iris. Whether surgical removal of this primary insult can lead to a successful intraocular pressure (IOP) control remains unclear. Methods: Case-series. Patients with IOP elevation and clinical signs of pigment dispersion were screened for a diagnosis of iatrogenic IOL-related pigment dispersion. Results: Three patients in which the IOL or the IOL-bag complex caused a pigment dispersion through a repetitive iris chafing were selected. In two cases, replacement of a sulcus-based single-piece IOL (patient 1) or a sub-luxated in-the-bag IOL (patient 2) by an anterior-chamber (AC) iris-fixed IOL led to a sustained decrease in IOP. In the third case, extensive iris atrophy and poor anatomical AC parameters for IOL implantation precluded further surgical intervention. Conclusion: IOL-exchange appears to be a useful tool in the management of iatrogenic pigment dispersion glaucoma due to inappropriate IOL implantation. This cause-oriented approach seems to be effective in controlling IOP, but should be offered only if safety criteria are met. How to cite this article: Van Mierlo C, Abegao Pinto L, Stalmans I. Surgical Management of Iatrogenic Pigment Dispersion Glaucoma. J Curr Glaucoma Pract 2015;9(1):28-32.

  6. Flat Electroretinography and Acute Visual Loss After Ocriplasmin Injection for Vitreomacular Adhesion Complicating Macular Schisis.

    PubMed

    Hale, Benjamin P; Au, Angela K; Falk, Naomi S; Bhatnagar, Pawan; Beer, Paul M

    2015-09-01

    A 53-year-old woman with macular and diffuse retinoschisis complicated by presumed vitreomacular traction underwent unilateral intravitreal ocriplasmin injection. Within hours after injection, she noted a loss of vision and the perception of "negative" images in the treated eye. Electrophysiologic testing revealed flat waveforms, and optical coherence tomography (OCT) showed initial decreased central macular thickness at day 1, followed by massive increased macular thickness with subfoveal neurosensory retinal detachment at 1 week. Her central macular thickness on OCT slowly returned to baseline during a period of 1 month until development of a macula-off rhegmatogenous retinal detachment at 6 months after injection. The authors believe this unique case of vitreomacular adhesion and macular schisis complicated by post-injection visual loss and electroretinography changes may offer further insight into this unusual complication. PMID:26431307

  7. Surface modification for aluminium pigment inhibition.

    PubMed

    Karlsson, Philip; Palmqvist, Anders E C; Holmberg, Krister

    2006-12-21

    This review concerns surface treatment of aluminium pigments for use in water borne coatings. Aluminium pigments are commonly used in coatings to give a silvery and shiny lustre to the substrate. Such paints and inks have traditionally been solvent borne, since aluminium pigment particles react with water. For environmental and health reasons solvent borne coatings are being replaced by water borne and the aluminium pigments then need to be surface modified in order to stand exposure to water. This process is called inhibition and both organic and inorganic substances are used as inhibiting agents. The organic inhibiting agents range from low molecular weight substances, such as phenols and aromatic acids, via surfactants, in particular alkyl phosphates and other anionic amphiphiles, to high molecular weight compounds, such as polyelectrolytes. A common denominator for them all is that they contain a functional group that interacts specifically with aluminium at the surface. A particularly strong interaction is obtained if the inhibiting agent contains functional groups that form chelating complex with surface Al(III). Encapsulation of the pigment can be made by in situ polymerization at the surface of the pigment and a recent approach is to have the polymerization occur within a double layer of adsorbed surfactant. The inorganic route is dominated by coating with silica, and recent progress has been made using an alkoxide, such as tetraethoxysilane as silica precursor. Such silica coated aluminium pigments are comparable in performance to chromate inhibited pigments and thus offer a possible heavy metal-free alternative. There are obvious connections between surface modifications made to prevent the pigment to react with water and inhibition of corrosion of macroscopic aluminium surfaces. PMID:17239333

  8. 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

  9. Glucose metabolism in rat retinal pigment epithelium.

    PubMed

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress. PMID:16475003

  10. Aqueous cytokines as predictors of macular edema in non-diabetic patients following uncomplicated phacoemulsification cataract surgery

    PubMed Central

    Chu, Liqun; Wang, Bingsong; Xu, Bing

    2013-01-01

    Purpose To ascertain whether cytokines in the aqueous humor can predict macular edema (ME) in non-diabetic patients following uncomplicated phacoemulsification cataract surgery. Methods Undiluted aqueous humor samples were obtained from 288 consecutive non-diabetic patients (288 eyes; 132 men and 156 women) who underwent cataract surgery. Macular edema was defined as an increase in the foveal center point thickness (FCPT) more than 30% from the preoperative baseline using optical coherence tomography 4 weeks after cataract surgery. The concentrations of 27 cytokines were measured in aqueous humor samples using the multiplex bead immunoassay. Results No major intraoperative complications occurred. The incidence of ME was 8.13% (23 patients) 4 weeks after cataract surgery. Compared to the ME (-) patients, the concentrations of interleukin-1β (IL-1β; p=0.016), IL-6 (p=0.013), monocyte chemotactic protein-1 (MCP-1; p=0.030), and vascular endothelial growth factor (VEGF; p=0.033) in the ME (+) patients were significantly higher. In addition, the aqueous humor levels of IL-1β (r=0.376), IL-6 (r=0.418), MCP-1 (r=0.348), and VEGF (r=0.375) positively correlated with the postoperative FCPT. However, the aqueous humor levels of IL-10 (p=0.017) were significantly lower in patients with ME and were negatively correlated with the postoperative FCPT (r=–0.424). Conclusions IL-1β, IL-6, MCP-1, VEGF, and IL-10 may be potential predictors of postoperative macular thickness in non-diabetic patients following uncomplicated phacoemulsification cataract surgery. PMID:24319335

  11. Evaluation of Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness after Vitrectomy with Internal Limiting Membrane Peeling for Idiopathic Macular Holes

    PubMed Central

    Velázquez-Villoria, Álvaro; Zapata, Miguel A.; Figueroa, Marta S.; Suárez-Leoz, Marta; Arrevola, Luis; Teijeiro, María-Ángeles; García-Layana, Alfredo

    2014-01-01

    Purpose. To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral-domain optical coherence tomography (SD-OCT). Methods. 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA). Results. No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. Conclusion. SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole. PMID:25110679

  12. The acute effect of oral acetazolamide on macular blood flow.

    PubMed

    Grunwald, J E; Zinn, H

    1992-03-01

    Acetazolamide has been shown to be beneficial in the treatment of macular edema. To investigate whether this effect is associated with changes in the retinal circulation, the acute effect of oral acetazolamide on macular blood flow was studied in 20 healthy volunteers. The blue-field simulation technique, a noninvasive method enabling the quantitation of the number (N) and mean velocity (Vm) of leukocytes flowing in the subject's own macular capillaries was used in this study. On two different occasions, separated by 3 or more days, 20 subjects adjusted Vm and N of computer-simulated leukocytes moving on a video screen to match those of their own entoptically perceived leukocytes before and 3 hr after a double-blind, randomized administration of 500 mg acetazolamide or placebo capsules. Ten trials were done, and the velocities were averaged. After acetazolamide ingestion, there was a nonsignificant average change from baseline in Vm (2.5 +/- 23% [+/- one standard deviation]; P greater than 0.1, by paired student t-test) and N (6.9 +/- 25%, P greater than 0.1). After placebo ingestion, the average changes from baseline in Vm and N also were not statistically significant (-1 +/- 18% and 14.9 +/- 30.3%, respectively). Furthermore, when compared with the changes measured after placebo intake, acetazolamide ingestion was associated with a nonsignificant 4.3 +/- 28.7% change in Vm (P greater than 0.1) and a -8 +/- 30.9% change in N (P greater than 0.1). With 20 subjects tested, the calculated average minimum change in leukocyte velocity that could have been detected with this technique (P less than 0.05, by paired student t-test) is about 9%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1544778

  13. Intravitreal pegaptanib for the treatment of ischemic diabetic macular edema

    PubMed Central

    Kiire, Christine A; Morjaria, Rupal; Rudenko, Anna; Fantato, Alexina; Smith, Lewis; Smith, Amy; Chong, Victor

    2015-01-01

    Purpose Pegaptanib has been shown to be effective in treating diabetic macular edema (DME). In the original Phase II/III trial, however, patients with macular ischemia were excluded. In this study, we treated patients with ischemic DME. Methods Macular ischemia was defined as a 30% increase in the area of the foveal avascular zone (FAZ) at 45 seconds on fundus fluorescein angiography. In addition, the participants had diffuse foveal-involving DME with a central subfield thickness (CST) of >300 μm on spectral-domain optical coherence tomography. Five intravitreal pegaptanib injections were given 6 weeks apart. The final study visit was 6 weeks after the fifth injection. The primary outcome was change in the size of FAZ. Secondary outcomes were change in best-corrected visual acuity (BCVA) and the change in CST. Results Thirty participants were enrolled. Three were unable to complete the full course of treatment. Their outcomes were carried forward for the first part of this analysis. There was no statistically significant change in the mean size of the FAZ from baseline to the final visit. Subclassifying participants as those with minimal/moderate ischemia (16 participants, FAZ area <1,000 pixels) and those with more severe ischemia (14 participants, FAZ area >1,000 pixels) also showed no statistically significant change in the mean area of the FAZ. On average, BCVA increased and CST decreased from baseline to the final visit, but these changes were not statistically significant. Using per protocol analysis on those participants who completed the full course of treatment, the mean BCVA incr