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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. [Atrophy of retinal pigment epithelium after macular hole surgery].

    PubMed

    Cerbulescu, Beatrice; Crstocea, B; Buliga, Simona; Gheorghieva, Valeria; Taina, Ana-Lavinia

    2010-01-01

    We present three cases of macular hole. After macular surgery we observed good anatomical results (closed macular holes) but poor functional results. We try to identified the element who produced atrophy of retinal pigment epithelium. PMID:20540371

  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 Optical Density Measured by Heterochromatic Modulation Photometry

    PubMed Central

    Huchzermeyer, Cord; Schlomberg, Juliane; Welge-Lssen, Ulrich; Berendschot, Tos T. J. M.; Pokorny, Joel; Kremers, Jan

    2014-01-01

    Purpose To psychophysically determine macular pigment optical density (MPOD) employing the heterochromatic modulation photometry (HMP) paradigm by estimating 460 nm absorption at central and peripheral retinal locations. Methods For the HMP measurements, two lights (B: 460 nm and R: 660 nm) were presented in a test field and were modulated in counterphase at medium or high frequencies. The contrasts of the two lights were varied in tandem to determine flicker detection thresholds. Detection thresholds were measured for different R:B modulation ratios. The modulation ratio with minimal sensitivity (maximal threshold) is the point of equiluminance. Measurements were performed in 25 normal subjects (11 male, 14 female; age: 3011 years, mean sd) using an eight channel LED stimulator with Maxwellian view optics. The results were compared with those from two published techniques one based on heterochromatic flicker photometry (Macular Densitometer) and the other on fundus reflectometry (MPR). Results We were able to estimate MPOD with HMP using a modified theoretical model that was fitted to the HMP data. The resultant MPODHMP values correlated significantly with the MPODMPR values and with the MPODHFP values obtained at 0.25 and 0.5 retinal eccentricity. Conclusions HMP is a flicker-based method with measurements taken at a constant mean chromaticity and luminance. The data can be well fit by a model that allows all data points to contribute to the photometric equality estimate. Therefore, we think that HMP may be a useful method for MPOD measurements, in basic and clinical vision experiments. PMID:25354049

  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. 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

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

    NASA Astrophysics Data System (ADS)

    Delori, Franois 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.

  12. 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

  13. Macular pigment optical density spatial distribution measured in a subject with oculocutaneous albinism

    PubMed Central

    Putnam, Christopher M.; Bland, Pauline J.

    2014-01-01

    Purpose Previous studies of macular pigment optical density (MPOD) distribution in individuals with oculocutaneous albinism (OCA) have primarily used objective measurement techniques including fundus reflectometry and autofluorescence. We report here on a subject with OCA and their corresponding MPOD distribution assessed through heterochromatic flicker photometry (HFP). Methods A subject with a history of OCA presented with an ocular history including strabismus surgery of the LE with persistent amblyopia and mild, latent nystagmus. Best corrected visual acuity was 20/25- RE and 20/40- LE. Spectral domain optical coherence tomography (SD-OCT) and fundus photography were also obtained. Evaluation of MPOD spatial distribution up to 8 degrees eccentricity from the fovea was performed using HFP. Results SD-OCT indicated a persistence of multiple inner retinal layers within the foveal region in the RE and LE including symmetric foveal thickening consistent with foveal hypoplasia. Fundus photography showed mild retinal pigmented epithelial (RPE) hypopigmentation and a poorly demarcated macula. OriginPro 9 was used to plot MPOD spatial distribution of the subject and a 33-subject sample. The OCA subject demonstrated a foveal MPOD of 0.10 with undetectable levels at 6 degrees eccentricity. The study sample showed a mean foveal MPOD of 0.34 and mean 6 degree eccentricity values of 0.03. Conclusions Consistent with previous macular pigment (MP) studies of OCA, overall MPOD is reduced in our subject. Mild phenotypic expression of OCA with high functional visual acuity may represent a Henle fiber layer amenable to additional MP deposition. Further study of MP supplementation in OCA patients is warranted. PMID:25323647

  14. 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-?-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.

  15. 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.

  16. 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

  17. 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 0.480.18. Patients with early AMD (0.520.19) tended to have higher MPOD levels than healthy people (0.470.17), 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

  18. 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

  19. 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

  20. 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.

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

    PubMed

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

    2015-11-01

    Heterochromatic flicker photometry (HFP) is the most common technique of measuring macular pigment optical density (MPOD). Some data strongly suggest that HFP samples MPOD specifically at the edge of center-fixated circular stimuli. Other data have led to the conclusion that HFP samples over the entire area of the stimulus. To resolve this disparity, MPOD was measured using HFP and a series of solid discs of varying radii (0.25 to 2.0 deg) and with thin annuli corresponding to the edge of those discs. MPOD assessed with the two methods yielded excellent correspondence and linearity: Y=0.01+0.98X , r=0.96. A second set of experiments showed that if a disc stimulus is adjusted for no-flicker (the standard procedure) and simply reduced in size, no flicker is observed despite the higher level of MPOD in the smaller area. Taken together, these results confirm that MPOD is determined at the edge of the measuring stimulus when using stimulus sizes in the range that is in dispute (up to a radius of 0.75 deg). The basis for this edge effect can be explained by quantitative differences in the spatial-temporal properties of the visual field as a function of angular distance from the fixation point. PMID:26562031

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

    PubMed Central

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

    2010-01-01

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

  3. 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

  4. 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

  5. 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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  8. 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

  9. Markers of lutein and zeaxanthin status in two age groups of men and women: dietary intake, serum concentrations, lipid profile and macular pigment optical density

    PubMed Central

    2014-01-01

    Background & aims Lutein and zeaxanthin accumulate in retina (macular pigment). Their nutritional status can be assessed using dietary or biochemical markers and both have been associated with macular pigment optical density. We proposed to assess dietary and status markers of lutein and zeaxanthin in a group of healthy Spanish volunteers, considering the potential influence of age, gender and serum lipids to investigate the predictors of the macular pigment optical density. Methods Serum lutein and zeaxanthin concentrations, dietary intake and macular pigment optical density were determined in 108 healthy men and women (2035 and 4565 years), using high-performance liquid chromatography, 3-day food records and heterochromic flicker photometry, respectively. MannWhitney U-test, Spearman correlation coefficient and multivariate regression analysis were used for the statistical study. Results Serum concentrations and dietary intake of lutein plus zeaxanthin (p?macular pigment optical density was lower (p?=?0.038). The highest correlation coefficients between intake and serum were for fruit and serum lutein (??=?0.452, p?Macular pigment optical density correlated with serum xanthophylls (??=?0.223, p?=?0.02) and fruit and vegetable intake (??=?0.350, p?=?0.0002), showing highest correlations when lutein and zeaxanthin were expressed in relation to serum lipids in older subjects (??=?0.262, p?=?0.006). Multivariate regression analysis identified age and serum lutein as major predictors of macular pigment optical density (total sample), and a coefficient of determination of 29.7% for the model including lutein?+?zeaxathin/cholesterol?+?triglycerides, sex and fruit?+?vegetables in the older group. Conclusions The establishment of normal/reference ranges for serum lutein and zeaxanthin should consider age ranges and be expressed in relation to lipid concentrations, at least in subjects over 45years, as this could influence macular pigment optical density. The macular pigment optical density showed age-specific correlations with lutein plus zeaxanthin expressed in relation to serum lipid concentrations as well as with the fruit and vegetable intake. PMID:24889185

  10. 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

  11. Progression of Retinal Pigment Epithelial Atrophy in Antiangiogenic Therapy of Neovascular Age-Related Macular Degeneration

    PubMed Central

    Schtze, Christopher; Wedl, Manuela; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K.; Schmidt-Erfurth, Ursula

    2015-01-01

    Purpose To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Design Prospective interventional case series. Methods setting: Clinical practice. study population: Thirty patients (31 eyes) with treatment-nave neovascular AMD. observation procedures: Standard intravitreal therapy (0.5mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. main outcome measures: RPE response, geographic atrophy (GA) progression. Results Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77mm2 at 12months to 1.10mm2 (standard deviation= 1.09mm2) at 24months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Conclusions Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. PMID:25769245

  12. 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

  13. Phototoxic Action Spectrum on a Retinal Pigment Epithelium Model of Age-Related Macular Degeneration Exposed to Sunlight Normalized Conditions

    PubMed Central

    Arnault, Emilie; Barrau, Coralie; Nanteau, Cline; Gondouin, Pauline; Bigot, Karine; Vinot, Franoise; Gutman, Emmanuel; Fontaine, Valrie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, Jos-Alain; Picaud, Serge

    2013-01-01

    Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye. PMID:24058402

  14. 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

  15. 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.

  16. 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...

  17. 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

  18. 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

  19. 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

  20. The association between macular pigment optical density and CFH, ARMS2, C2/BF, and C3 genotype.

    PubMed

    Loane, Edward; Nolan, John M; McKay, Gareth J; Beatty, Stephen

    2011-11-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk for this condition may be classified as genetic or environmental, with an interaction between such factors predisposing to this disease. This study investigated the relationship between AMD risk genes, macular pigment optical density (MPOD), which may protect against AMD, and serum concentrations of the macular carotenoids, lutein (L) and zeaxanthin (Z). This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. We also calculated MPOD Area as the area of MP under the spatial profile curve, to reflect MP across the macula. Serum L and Z were measured by HPLC. Genotyping of tag SNPs in the genes CFH, ARMS2, C3, C2 and BF was undertaken with multiplex polymerase chain reaction (PCR) and primer extension methodology (ABI Snapshot, ABI Warrington UK) on DNA extracted from peripheral blood. The mean SD (range) age of the subjects in this study was 48 11 (21-66) years. There was a statistically significant association between CFH genotype and family history of AMD, with subjects having two non-risk CFH haplotypes (n = 35), or one non-risk and one protective CFH haplotype (n = 33), being significantly more likely to have a negative family history of AMD (Pearson Chi square: p = 0.001). There was no significant association between the AMD risk genes investigated and either MPOD (One way ANOVA: p > 0.05) or serum concentrations of L or Z (One way ANOVA: p > 0.05, for both). Subjects who were homozygous for risk alleles of both CFH and ARMS2 (n = 4) had significantly lower MPOD at 0.5 and 1 retinal eccentricity (Independent samples t test: p < 0.05) and lower MPOD Area which approached statistical significance (Independent samples t test: p = 0.058), compared to other subjects (n = 291). In conclusion, this study did not detect an association between individual AMD risk genotypes and the putatively protective MP, or serum concentrations of its constituent carotenoids. However, the combination of homozygous risk alleles at both CFH and ARMS2 loci was associated with significantly lower MPOD centrally, despite comparable serum concentrations of the macular carotenoids. These findings suggest that the maculae of subjects at very high genetic risk of AMD represent a hostile environment for accumulation and/or stabilization of MP. PMID:21816153

  1. Resonant imaging of carotenoid pigments in the human retina

    NASA Astrophysics Data System (ADS)

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

    2002-06-01

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

  2. 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

  3. 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.

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

    PubMed

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

    2013-11-01

    This study compares invivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer()), dual-wavelength fundus autofluorescence (Heidelberg Spectralis() HRA+OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam() 200). MP was measured in one eye of 62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis. Agreement between the Densitometer and Spectralis was investigated at various eccentricities using a variety of quantitative and graphical methods, including: Pearson correlation coefficient to measure degree of scatter (precision), accuracy coefficient, concordance correlation coefficient (ccc), paired t-test, scatter and Bland-Altman plots. The relationship between max MP from the Visucam and central MP from the Spectralis and Densitometer was investigated using regression methods. Agreement was strong between the Densitometer and Spectralis at all central eccentricities (e.g. at 0.25 eccentricity: accuracy=0.97, precision=0.90, ccc=0.87). Regression analysis showed a very weak relationship between the Visucam and Densitometer (e.g. Visucam max on Densitometer central MP: R(2)=0.008, p=0.843). Regression analysis also demonstrated a weak relationship between MP measured by the Spectralis and Visucam (e.g. Visucam max on Spectralis central MP: R(2)=0.047, p=0.348). MP values obtained using the Heidelberg Spectralis are comparable to MP values obtained using the Densitometer. In contrast, MP values obtained using the Zeiss Visucam are not comparable with either the Densitometer or the Spectralis MP measuring devices. Taking cHFP as the current standard to which other MP measuring devices should be compared, the Spectralis is suitable for use in a clinical and research setting, whereas the Visucam is not. PMID:24007642

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. In vivo imaging of retinal pigment epithelium cells in age related macular degeneration

    PubMed Central

    Rossi, Ethan A.; Rangel-Fonseca, Piero; Parkins, Keith; Fischer, William; Latchney, Lisa R.; Folwell, Margaret A.; Williams, David R.; Dubra, Alfredo; Chung, Mina M.

    2013-01-01

    Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in the living human eye non-invasively by imaging the short-wavelength autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based on the assumption that all subjects have the same longitudinal chromatic aberration (LCA) correction, has proved difficult to use in diseased eyes, and in particular those affected by age-related macular degeneration (AMD). In this work, we improve Morgans method by accounting for chromatic aberration variations by optimizing the confocal aperture axial and transverse placement through an automated iterative maximization of image intensity. The increase in image intensity after algorithmic aperture placement varied depending upon patient and aperture position prior to optimization but increases as large as a factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm2, which is ~22 times below the current ANSI maximum permissible exposure. RPE cell morphologies that were strikingly similar to those seen in postmortem histological studies were observed in AMD eyes, even in areas where the pattern of fluorescence appeared normal in commercial fundus autofluorescence (FAF) images. This new method can be used to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health. PMID:24298413

  12. 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

  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. 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

  15. Three dimensional distribution of the vitelliform lesion, photoreceptors, and retinal pigment epithelium in the macula of patients with Best vitelliform macular dystrophy

    PubMed Central

    Kay, Christine N.; Abramoff, Michael D.; Mullins, Robert F.; Kinnick, Tyson R.; Lee, Kyuongmoo; Eyestone, Mari E.; Chung, Mina M.; Sohn, Elliott H.; Stone, Edwin M.

    2015-01-01

    Objective To describe the anatomical phenotypes of Best vitelliform macular dystrophy (BVMD) with spectraldomain optical coherence tomography (SD-OCT) in a large series of patients with confirmed mutations in the BEST1 gene. Methods In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene. Color fundus photographs and SD-OCT images were evaluated and compared with those of 15 age-matched controls (30 eyes). Using a validated 3-dimensional SD-OCT segmentation algorithm, we calculated the equivalent thickness of photoreceptors and the equivalent thickness of the retinal pigment epithelium for each patient. The photoreceptor equivalent thickness and the retinal pigment epithelium (RPE) equivalent thickness were compared in all patients, in a region of the macula outside the central lesion for patients with BVMD and outside the fovea in control patients. Paired t tests were used for statistical analysis. Results The SD-OCT findings revealed that the vitelliform lesion consists of material above the RPE and below the outer segment tips. Additionally, drusen-like deposition of sub-RPE material was notable, and several patients exhibited a sub-RPE fibrotic nodule. Patients with BVMD had a mean photoreceptor equivalent thickness of 28.3 ?m, and control patients had a mean photoreceptor equivalent thickness of 21.8 ?m, a mean difference of 6.5 ?m (P < .01), whereas the mean RPE equivalent thickness was not statistically different between patients with BVMD and control patients (P=.53). Conclusions The SD-OCT findings suggest that vitelliform material is located in the subretinal space and that BVMD is associated with diffuse photoreceptor outer segment abnormalities overlying a structurally normal RPE. Clinical Relevance: These findings provide new insight into the pathophysiology of BVMD and thus have implications for the development of therapeutic interventions. PMID:22084158

  16. 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

  17. Genetics Home Reference: Stargardt macular degeneration

    MedlinePLUS

    ... people with Stargardt macular degeneration, a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. ... acids ; gene ; inheritance ; inherited ; juvenile ; lipofuscin ; macula ; photoreceptor ; pigment ; prevalence ; protein ; recessive ; retina ; tissue ; toxic You may ...

  18. Genetics Home Reference: Vitelliform macular dystrophy

    MedlinePLUS

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

  19. 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: 46year-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: 45year-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

  20. Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: the LUNA study.

    PubMed

    Trieschmann, Meike; Beatty, Stephen; Nolan, John M; Hense, Hans Werner; Heimes, Britta; Austermann, Ulrike; Fobker, Manfred; Pauleikhoff, Daniel

    2007-04-01

    Macular pigment (MP), consisting of lutein (L) and zeaxanthin (Z), is believed to protect the retina from photo-oxidative damage. The current study investigates, in terms of MP optical density (MPOD) and serum concentrations of its constituent carotenoids, response to supplemental L and Z, and co-antioxidants. An intervention (I) group, consisting of 108 subjects (mean [+/-SD] age: 71.5 [+/-7.1] years), of which 92.6% exhibited features of age-related macular degeneration (AMD), received a daily supplement consisting of 12 mg L and 1 mg Z, both provided as ester 120 mg vitamin C, 17.6 mg vitamin E, 10 mg zinc, 40 microg selenium (Ocuvite Luteintrade mark) for a period of 6 months. MPOD was measured, by 2-wavelength autofluorescence (AF), on five occasions during the period of supplementation, and once again 3 months following discontinuation of the supplement. A control (C) group of 28 subjects (mean [+/-SD] age: 71.0 [+/-8.1] years), who received no dietary supplementation or modification, was examined at baseline and once again after a mean of 29.4 (+/-9.3) weeks. At baseline, mean (+/-SD) MPOD (at 0.5 degrees) was 0.504 (+/-0.197) and 0.525 (+/-0.189) in the I and C groups, respectively. There was a statistically significant increase in MPOD (at 0.5 degrees) for the I group (0.1 [+/-0.009]; p<0.0008), whereas no significant increase was seen in the C group (0.03 [+/-0.02]; p>0.05), over the period of supplementation. In order to classify supplemented subjects into quartiles, in terms of MPOD response, we calculated the difference between MPOD (at 0.5 degrees) at visit 6 and at baseline (visit 1). Quartile 1 (the "non-responder" quartile) displayed no increase in MPOD (at 0.5 degrees), in spite of rises seen in serum concentrations of L and Z. The three "responder" quartiles reached similar final plateaus of MPOD (at 0.5 degrees), reflected in final mean (+/-SEM) values of 0.59 (+/-0.04) optical density unit (ODU), 0.64 (+/-0.03) ODU and 0.64 (+/-0.03) ODU for quartiles 2, 3 and 4, respectively. Subjects with low baseline MPOD were more likely to exhibit a dramatic rise in MPOD, or to exhibit no rise in MPOD, in response to supplements than subjects with medium to high baseline MPOD values. Supplementation with 12 mg L and 1 mg Z, combined with co-antioxidants, resulted in an increase of MPOD at 0.5 degrees eccentricity in a majority of subjects, including those afflicted with AMD. However, there remains a substantial proportion of subjects for whom, in spite of rises in serum concentrations of L and Z in these subjects, MPOD augmentation in response to supplemental L, Z and co-antioxidants could not be detected over the study period, thus indicating that intestinal malabsorption of these carotenoids is not responsible for the lack of a macular response to such supplements. Further, our results suggest that saturable mechanisms play a role in the retinal capture and/or stabilisation of the macular carotenoids. PMID:17306793

  1. Vitreous levels of somatostatin in patients with chronic uveitic macular oedema

    PubMed Central

    Fonollosa, A; Coronado, E; Catalan, R; Gutierrez, M; Macia, C; Zapata, M A; Martinez-Alday, N; Simo, R; Garcia-Arumi, J

    2012-01-01

    Purpose Intravitreal somatostatin (SST) levels are decreased in patients with diabetic macular oedema. This deficit may be involved in the pathogenesis of this condition. The aim of the present study was to determine SST concentration in the vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and quiescent intraocular inflammation. Methods Plasma and vitreous fluid samples were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42 eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST concentration was measured by radioimmunoassay. Statistics: ?2-square test, MannWhitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and multivariant linear regression models. Results Plasma SST concentrations were similar in uveitic patients and controls (28.25?pg/ml (21.331) vs 28.7?pg/ml (2229.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic patients (1.590.38?mg/ml vs 0.730.32?mg/ml, P<0.0001). Vitreous SST was markedly lower in uveitic patients, both in absolute terms and after adjusting for total intravitreous protein concentration (39.37?pg/ml (6.16172) vs 486.73?pg/ml (4.71833), P<0.0001; 33.1?pg/mg (3.9215.74) vs 629.75?pg/mg (6.912024), P<0.0001). No correlations were found between plasma and vitreous concentration of SST in either group (?=0.191, P=0.57 and ?=0.49, P=0.66). There were no correlations between vitreous SST concentration and visual acuity or macular thickness in uveitic patients (?=0.302, P=0.31 and ?=0.45, P=0.13). Conclusions Intravitreous SST is decreased in patients with CUMO and quiescent intraocular inflammation. The deficit of SST may have a role in the pathogenesis of this condition. PMID:22878444

  2. 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 7.873.36 ?m , and is comparable to the mean inter-observer variability ( 7.812.56 ?m). 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

  3. High-resolution spectral domain optical coherence tomography findings in multifocal vitelliform macular dystrophy.

    PubMed

    Querques, Giuseppe; Regenbogen, Michael; Soubrane, Gisele; Souied, Eric H

    2009-01-01

    We describe the abnormalities seen in the mid periphery and posterior pole of two patients with multifocal vitelliform macular dystrophy as evaluated by high-definition spectral domain optical coherence tomography (HD-OCT). In patient 1, HD-OCT scans revealed, in the central area, a thicker and more reflective layer compared with the normal macula, located between the retinal pigment epithelium and the interface of the inner segment/outer segment, corresponding to the Verhoeff's membrane. Moreover, HD-OCT macular scans, as well as C-scans, revealed a slight hyper-reflective lesion just above an area of reduced reflectivity between the photoreceptor layer (interface of the inner segment and outer segment) and the Verhoeff's membrane. In patient 2, on HD-OCT macular scans, the layer corresponding to the interface of inner segment and outer segment of the photoreceptor, and the Verhoeff's membrane, appeared disrupted, whereas the retinal pigment epithelium layer appeared preserved. On the other hand, in both patient 1 and 2, the clinically evident vitelliform lesions outside the macular area appeared on HD-OCT scans either as small focal hyper-reflective lesions at the level of the retinal pigment epithelium/photoreceptor complex, either as a more pronounced diffuse thickening of the retinal pigment epithelium/photoreceptor complex, facing the deposition of lipofuscin reported on the histopathologic examination. These new findings would help in a further understanding of multifocal vitelliform macular dystrophy. PMID:19298908

  4. 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

  5. Endothelin-1 and Nitric Oxide Levels in Exudative Age-Related Macular Degeneration

    PubMed Central

    Totan, Y?ksel; Koca, Cemile; Erdurmu?, Mesut; Keskin, U?urcan; Yi?ito?lu, Ramazan

    2015-01-01

    Purpose: To evaluate plasma levels of endothelin-1 (ET-1) and nitric oxide (NO) in patients with exudative age-related macular degeneration (AMD). Methods: In this study, ET-1 levels, as well as nitrite plus nitrate concentrations as an indicator of plasma NO level, were measured in the plasma of 20 subjects with exudative AMD and compared with 20 healthy age and sex matched controls. Results: Mean plasma ET-1 level was significantly higher in exudative AMD patients as compared to control subjects (0.35 0.06 fmol/ml versus 0.17 0.03 fmol/ml, P = 0.015). Patients with exudative AMD also showed significantly lower mean plasma levels of nitrite plus nitrate as compared to the controls (58.9 2.7 mol/l versus 82.6 5.9 mol/l, P = 0.001). Conclusion: Increased concentrations of ET-1 and reduced levels of NO in the plasma may suggest an imbalance between vasoconstrictor and vasodilator agents, respectively, as a reflection of endothelial dysfunction in the pathogenesis of AMD. These findings may also imply the role of vasoconstriction in exudative AMD. PMID:26425317

  6. Serum paraoxonase 1 activity and lipid peroxidation levels in patients with age-related macular degeneration.

    PubMed

    Baskol, Gulden; Karakucuk, Sarper; Oner, Ayse Ozturk; Baskol, Mevlut; Kocer, Derya; Mirza, Ertugrul; Saraymen, Recep; Ustdal, Muzaffer

    2006-01-01

    Our objective was to investigate antioxidant paraoxonase 1 (PON1) activity together with malondialdehyde (MDA) levels to evaluate oxidative stress in patients with age-related macular degeneration (AMD), an important cause of blindness in the elderly population. Serum PON1 activity and MDA levels were analyzed in 37 patients with AMD and compared with 29 healthy controls using a spectrophotometric method. Serum MDA levels were significantly higher in the patient group (2.76 +/- 1.28 nmol/ml) than controls (1.00 +/- 0.36 nmol/ml; p < 0.001), whereas PON1 activity was lower in the patient group (132.27 +/- 63.39 U/l) than controls (312.13 +/- 136.23 U/l; p < 0.001). There was a negative correlation between MDA and PON1 levels (r = -0.470, p < 0.001). We conclude that the observed increase in MDA levels may be related to decreased PON1 activity; the present data also demonstrated that an obvious negative correlation between PON1 activity and MDA levels exists in patients with AMD. PON1 is also an antioxidant agent, therefore effective antioxidant therapy to inhibit lipid peroxidation is necessary and agents to increase PON1 activity may be a therapeutic option in AMD. PMID:16374043

  7. 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

  8. 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

  9. 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

  10. 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

  11. Age related macular degeneration

    PubMed Central

    2007-01-01

    Introduction Sight-threatening (late) age-related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with age. Early-stage disease is marked by normal vision, but retinal changes (drusen and pigment changes). Disease progression leads to worsening central vision, but peripheral vision is preserved. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression of early- or late-stage age-related macular degeneration; and exudative age-related macular degeneration? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiangiogenesis (using pegaptanib, ranibizumab, interferon alfa-2a, or anecortave acetate), antioxidant vitamins plus zinc, external beam radiation, laser treatment to drusen, photodynamic therapy with verteporfin, submacular surgery, thermal laser photocoagulation, transpupillary thermotherapy. PMID:19454069

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

    PubMed Central

    Tolentino, Michael

    2010-01-01

    Aim To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. Methods A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30120?days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275??m or less or thinning of 100??m or more (optical coherence tomography); visual acuity (VA) 20/2020/400. Intravitreal pegaptanib 0.3?mg was administered as maintenance every 6?weeks for 48?weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration. Results Of 568 enrolled subjects, 86% completed 1?year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20??m increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147?days after maintenance initiation). Conclusions An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD. PMID:20472746

  13. 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

  14. 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

  15. 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...

  16. Correlation of Vitamin D Levels with Pigmentation in Vitiligo Patients Treated with NBUVB Therapy.

    PubMed

    Sehrawat, Manu; Arora, Tarlok Chand; Chauhan, Amrita; Kar, Hemanta Kumar; Poonia, Amitabh; Jairath, Vijayeeta

    2014-01-01

    Cholecalciferol (vitamin D) might play a physiological role in photo-induced melanogenesis in human skin. We estimated the levels of 25-hydroxy vitamin D [25(OH)D] before, during, and after Narrow Band Ultraviolet B (NBUVB) radiation in patients of vitiligo and their correlation with NBUVB induced pigmentation. Thirty patients of vitiligo and equal number of age and sex matched controls were recruited for the study. Vitiligo patients were treated with NBUVB thrice weekly for 12 weeks. [25(OH)D] levels and Vitiligo Area and Severity Index (VASI) were calculated at 0 (baseline), 6, and 12 weeks. Baseline [25(OH)D] levels were measured in controls. Significant reduction in VASI score was observed after 12 weeks of therapy. Comparison and correlation between mean improvement in VASI and [25(OH)D] levels at 12 weeks showed moderate correlation, and the results were statistically insignificant. Mean reduction in VASI and increase in [25(OH)D] levels after 12 weeks of NBUVB showed moderate correlation. Thus, vitamin D might play a significant role in photo-induced melanogenesis. However, there might be additional effects of the phototherapy on melanogenesis. The complete mechanism of NBUVB induced pigmentation in vitiligo needs to be elucidated. PMID:25006488

  17. Correlation of Vitamin D Levels with Pigmentation in Vitiligo Patients Treated with NBUVB Therapy

    PubMed Central

    Sehrawat, Manu; Arora, Tarlok Chand; Chauhan, Amrita; Kar, Hemanta Kumar; Poonia, Amitabh; Jairath, Vijayeeta

    2014-01-01

    Cholecalciferol (vitamin D) might play a physiological role in photo-induced melanogenesis in human skin. We estimated the levels of 25-hydroxy vitamin D [25(OH)D] before, during, and after Narrow Band Ultraviolet B (NBUVB) radiation in patients of vitiligo and their correlation with NBUVB induced pigmentation. Thirty patients of vitiligo and equal number of age and sex matched controls were recruited for the study. Vitiligo patients were treated with NBUVB thrice weekly for 12 weeks. [25(OH)D] levels and Vitiligo Area and Severity Index (VASI) were calculated at 0 (baseline), 6, and 12 weeks. Baseline [25(OH)D] levels were measured in controls. Significant reduction in VASI score was observed after 12 weeks of therapy. Comparison and correlation between mean improvement in VASI and [25(OH)D] levels at 12 weeks showed moderate correlation, and the results were statistically insignificant. Mean reduction in VASI and increase in [25(OH)D] levels after 12 weeks of NBUVB showed moderate correlation. Thus, vitamin D might play a significant role in photo-induced melanogenesis. However, there might be additional effects of the phototherapy on melanogenesis. The complete mechanism of NBUVB induced pigmentation in vitiligo needs to be elucidated. PMID:25006488

  18. Determination of N-retinylidene-N-retinylethanolamine (A2E) levels in central and peripheral areas of human retinal pigment epithelium.

    PubMed

    Adler, Leopold; Boyer, Nicholas P; Anderson, David M; Spraggins, Jeffrey M; Schey, Kevin L; Hanneken, Anne; Ablonczy, Zsolt; Crouch, Rosalie K; Koutalos, Yiannis

    2015-10-28

    The bis-retinoid N-retinylidene-N-retinylethanolamine (A2E) is one of the major components of lipofuscin, a fluorescent material that accumulates with age in the lysosomes of the retinal pigment epithelium (RPE) of the human eye. Lipofuscin, as well as A2E, exhibit a range of cytotoxic properties, which are thought to contribute to the pathogenesis of degenerative diseases of the retina such as Age-related Macular Degeneration. Consistent with such a pathogenic role, high levels of lipofuscin fluorescence are found in the central area of the human RPE, and decline toward the periphery. Recent reports have however suggested a surprising incongruence between the distributions of lipofuscin and A2E in the human RPE, with A2E levels being lowest in the central area and increasing toward the periphery. To appraise such a possibility, we have quantified the levels of A2E in the central and peripheral RPE areas of 10 eyes from 6 human donors (ages 75-91 years) with HPLC and UV/VIS spectroscopy. The levels of A2E in the central area were on average 3-6 times lower than in peripheral areas of the same eye. Furthermore, continuous accumulation of selected ions (CASI) imaging mass spectrometry showed the presence of A2E in the central RPE, and at lower intensities than in the periphery. We have therefore corroborated that in human RPE the levels of A2E are lower in the central area compared to the periphery. We conclude that the levels of A2E cannot by themselves provide an explanation for the higher lipofuscin fluorescence found in the central area of the human RPE. PMID:26323192

  19. 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 ...

  20. Treatment for Macular Telangiectasia Type 2.

    PubMed

    Charbel Issa, Peter; Kupitz, Elke H; Heeren, Tjebo F C; Holz, Frank G

    2016-01-01

    Macular telangiectasia (MacTel) type 2 is a bilateral disease of unknown cause with localized retinal degeneration and characteristic changes of the retinal vasculature. Funduscopic findings include reduced retinal transparency, crystalline deposits, ectatic capillaries, blunted venules, retinal pigment plaques, foveal atrophy and neovascular complexes. Leakage of telangiectatic macular capillaries is a characteristic finding on fluorescein angiography, and neurosensory atrophy may be present on optical coherence tomography images. Furthermore, there is a specific depletion of macular pigment in the central retina. Depending on the development of neovascular membranes, a nonproliferative and a proliferative (neovascular) disease stage may be distinguished. To date, there is no evidence for an effective treatment of nonproliferative MacTel type 2. Patients with proliferative MacTel type 2 and hence decreasing visual function may benefit from intravitreal application of vascular endothelial growth factor inhibitors. Early treatment and a small size of the neovascular membrane might be predictive factors for visual function outcome. PMID:26501828

  1. Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruchs 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)/Bruchs 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 (~8590% 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 (~1015% 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

  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. Pigmentation above the constitutive level: an indicator of excimer laser radiation-induced erythema in Koreans.

    PubMed

    Choi, Jee-Woong; Na, Se-Young; Chung, Mi-Young; Na, Jung-Im; Huh, Chang-Hun; Youn, Sang-Woong; Kang, Hee-Young; Park, Kyoung-Chan

    2012-07-01

    Ultraviolet (UV) irradiation induces skin erythema, but it is not clear which factors have the greatest effects on UV sensitivity. Six healthy Korean adult men were enrolled and their melanin index (MI) and increment of erythema index (?EI) were measured. In each individual, 12 different sites were selected and 36 spots were irradiated with a single shot of monochromatic excimer laser with a dose of 350 mJ/cm(2) . The sites were categorized into three groups based on the cumulative sun exposure: UZ, unexposed zones; FEZ, frequently exposed zones; and IEZ, intermittently exposed zones. The sun exposure indexes (SEI) were also calculated based on previously described methods. ?EI, MI and SEI were measured and calculated. The ?EI of UZ was significantly higher than that of FEZ, but lower than that of IEZ. In general, there was a significant relationship between ?EI and MI (R(2) = 0.135). However, IEZ did not show significant results. In contrast, there was a stronger relationship between ?EI and SEI (R(2) = 0.344). Overall, the values were significantly higher for the SEI (0.541 [UZ], 0.281 [IEZ] and 0.228 [FEZ]) than for MI (0.311 [UZ], 0.011 [IEZ] and 0.073 [FEZ]). There were significant site variations in UV sensitivity along with skin pigmentation. In addition, significant differences were observed according to the exposure frequency. The SEI was found to be strongly correlated with UV sensitivity. These results suggest that the induced level of pigmentation above the constitutive level will be a better indicator for UV sensitivity than baseline MI. PMID:22506614

  4. 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

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

    PubMed

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

    2016-01-01

    Protein oxidative degradation is implicated in a wide range of deleterious effects. For human hair, this oxidative damage can lead to significant observable changes in fiber physical and visual properties. A redox proteomic approach was applied to map molecular modification in human hair proteins and correlate this modification with the abundance of copper (II) ions, the levels of UV exposure and the general level of hair pigmentation. An increase in oxidative modification was observed with increasing copper (II) ion levels, regardless of the pigmentation level. Significantly, increased protein oxidative modification was also observed to occur in both lightly and darkly pigmented hair tresses even in the absence of irradiation, albeit at lower relative levels. Modification levels increased with increased copper (II) ion concentration. This new finding indicates that the level of copper (II) ions in human hair plays a key role in mediating protein oxidation, with or without exposure to UV light. Overall, these results strongly suggest that minimization of the level of copper (II) ions in human hair will mitigate and/or slow protein oxidative modification and therefore lower overall hair damage. PMID:26451514

  7. 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

  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. Sequential in-office vitreous aspirates demonstrate vitreous matrix metalloproteinase 9 levels correlate with the amount of subretinal fluid in eyes with wet age-related macular degeneration

    PubMed Central

    Pfahler, Scott M.; Hines, Joshua C.; Lovelace, Ann S.; Glaser, Bert M.

    2012-01-01

    Purpose To evaluate levels of 37 native pathway proteins of the vitreous proteome from a subset of wet age-related macular degeneration (AMD) patients with and without subretinal fluid (SRF). Methods A total of 62 consecutive samples were aspirated from 12 patients with AMD, six who had SRF at baseline, and six who did not have SRF at any point during the study. Vitreous levels of the 37 native pathway proteins were analyzed in these patients using reverse phase protein microarray technology. At each visit, at which the 62 samples were taken, SRF and central retinal thickness were measured. These values were then compared to the relative intensity level of the 37 proteins screened. Results In the subset of AMD patients with SRF, the average matrix metalloproteinase 9 (MMP-9), interleukin (IL)-12, Abelson murine leukemia viral oncogene homolog 1 (cABL) Thr735, heme oxygenase-1, Musashi, platelet-derived growth factor receptor beta Tyr751 (PDGFR?), IL-8, and BCL-2 associated death promoter (BAD) Ser112 levels in the vitreous were found to be significantly different with a 21%82% increase in expression compared to those without SRF (p<0.0001). Within the SRF group, there was a positive correlation between the vitreous MMP-9 levels and the SRF level. MMP-9 levels in the vitreous proteome varied with the level of SRF but not retinal edema. Compared to patients without SRF, the patients with initial SRF had persistent or progressive disease. Conclusions This is the first prospective case series sequentially monitoring the vitreous proteome in patients with wet AMD. The results suggest that MMP-9 is a proteomic biomarker of SRF accumulation, separate from macular edema. PMID:22773904

  10. Oxidative damage and age-related macular degeneration.

    PubMed

    Winkler, B S; Boulton, M E; Gottsch, J D; Sternberg, P

    1999-11-01

    This article provides current information on the potential role of oxidation in relation to age-related macular degeneration (AMD). The emphasis is placed on the generation of oxidants and free radicals and the protective effects of antioxidants in the outer retina, with specific emphasis on the photoreceptor cells, the retinal pigment epithelium and the choriocapillaris. The starting points include a discussion and a definition of what radicals are, their endogenous sources, how they react, and what damage they may cause. The photoreceptor/pigment epithelium complex is exposed to sunlight, is bathed in a near-arterial level of oxygen, and membranes in this complex contain high concentrations of polyunsaturated fatty acids, all considered to be potential factors leading to oxidative damage. Actions of antioxidants such as glutathione, vitamin C, superoxide dismutase, catalase, vitamin E and the carotenoids are discussed in terms of their mechanisms of preventing oxidative damage. The phototoxicity of lipofuscin, a group of complex autofluorescent lipid/protein aggregates that accumulate in the retinal pigment epithelium, is described and evidence is presented suggesting that intracellular lipofuscin is toxic to these cells, thus supporting a role for lipofuscin in aging and AMD. The theory that AMD is primarily due to a photosensitizing injury to the choriocapillaris is evaluated. Results are presented showing that when protoporphyric mice are exposed to blue light there is an induction in the synthesis of Type IV collagen synthesis by the choriocapillary endothelium, which leads to a thickened Bruch's membrane and to the appearance of sub-retinal pigment epithelial fibrillogranular deposits, which are similar to basal laminar deposits. The hypothesis that AMD may result from oxidative injury to the retinal pigment epithelium is further evaluated in experiments designed to test the protective effects of glutathione in preventing damage to cultured human pigment epithelial cells exposed to an oxidant. Experiments designed to increase the concentration of glutathione in pigment epithelial cells using dimethylfumarate, a monofunctional inducer, are described in relation to the ability of these cells to survive an oxidative challenge. While all these models provide undisputed evidence of oxidative damage to the retinal pigment epithelium and the choriocapillaris that is both light- and oxygen-dependent, it nevertheless is still unclear at this time what the precise linkage is between oxidation-induced events and the onset and progression of AMD. PMID:10562656

  11. Complications of Macular Peeling

    PubMed Central

    Asencio-Duran, Mnica; Manzano-Muoz, Beatriz; Vallejo-Garca, Jos Luis; Garca-Martnez, Jess

    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. [Age related macular degeneration].

    PubMed

    Helgadttir, Gudleif; Jnasson, Fridbert; Sigurdsson, Haraldur; Magnsson, Kristinn P; Stefnsson, Einar

    2006-10-01

    Age-related macular degeneration (AMD) is the main reason for blindness today in the western hemisphere. According to Bjrn Olafsson, who was the first ophthalmologist in Iceland a century ago, this disease was not found in Iceland. In the blindness-registry of 1950 6% blindness was due to this disease. Today, AMD is responsible for 54% of legal blindness in Iceland. The incidence of the disease increases with age. Heredity and environmental factors are thought to influence its etiology. Indirect methods, including twin studies and increased frequency of this disease in some families, have demonstrated that hereditary factors may be important. This has been confirmed recently by demonstrating that genes on chromosome 1 and chromosome10 play a role. This disease is classified as early stage, with drusen and pigmentary changes and insignificant visual loss. Treatment options for this stage are limited. The use of vitamin E and C and Zinc has, however, been shown to delay its progress. The second and end stage involves visual loss, either as a dry form with pigment epithelial atrophy or wet form, with new vessel formation. Treatment options for the dry form are limited. The second form is more common in Iceland than in other countries. Treatment options for the wet form have increased. Localised laser and drug treatment to neovascular membranes, either alone or as a combination treatment with drugs that have anti-proliferate effect on new vessels (anti-VEGF) are increasingly used. New treatment methods are also used in assisting those that are already visually handicapped. The use of computers is increasing as are the patients' computer skills. As the number of the elderly increases, AMD will be an increasing health problem in Iceland as in other Western countries. It is therefore important to improve the treatment options and the service and counselling of patients. PMID:17062902

  14. Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels.

    PubMed

    Ristau, Tina; Paun, Constantin; Ersoy, Lebriz; Hahn, Moritz; Lechanteur, Yara; Hoyng, Carel; de Jong, Eiko K; Daha, Mohamed R; Kirchhof, Bernd; den Hollander, Anneke I; Fauser, Sascha

    2014-01-01

    Age-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD associated risk genes. Component 3 (C3) and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH) genes and complement factor B (CFB) genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002), higher age (p = 1.56 10(-7)), AMD phenotype (p = 1.15 10(-11)) and the two SNPs in the C3 gene rs6795735 (p = 0.04) and rs2230199 (p = 0.04). Lower C3d/C3 ratios were found for diabetes (p = 2.87 10(-6)), higher body mass index (p = 1.00 10(-13)), the SNPs rs1410996 (p = 0.0001), rs800292 (p = 0.003), rs12144939 (p = 4.60 10(-6)) in CFH, rs4151667 (p = 1.01 10(-5)) in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation. PMID:24675670

  15. Carotenoid accumulation in orange-pigmented Capsicum annuum fruit, regulated at multiple levels

    PubMed Central

    Rodriguez-Uribe, Laura; Guzman, Ivette; Rajapakse, Wathsala; Richins, Richard D.; OConnell, Mary A.

    2012-01-01

    The pericarp of Capsicum fruit is a rich dietary source of carotenoids. Accumulation of these compounds may be controlled, in part, by gene transcription of biosynthetic enzymes. The carotenoid composition in a number of orange-coloured C. annuum cultivars was determined using HPLC and compared with transcript abundances for four carotenogenic enzymes, Psy, LcyB, CrtZ-2, and Ccs determined by qRT-PCR. There were unique carotenoid profiles as well as distinct patterns of transcription of carotenogenic enzymes within the seven orange-coloured cultivars. In one cultivar, Fogo, carrying the mutant ccs-3 allele, transcripts were detected for this gene, but no CCS protein accumulated. The premature stop termination in ccs-3 prevented expression of the biosynthetic activity to synthesize the capsanthin and capsorubin forms of carotenoids. In two other orange-coloured cultivars, Orange Grande and Oriole, both with wild-type versions of all four carotenogenic enzymes, no transcripts for Ccs were detected and no red pigments accumulated. Finally, in a third case, the orange-coloured cultivar, Canary, transcripts for all four of the wild-type carotenogenic enzymes were readily detected yet no CCS protein appeared to accumulate and no red carotenoids were synthesized. In the past, mutations in Psy and Ccs have been identified as the loci controlling colour in the fruit. Now there is evidence that a non-structural gene may control colour development in Capsicum. PMID:21948863

  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. 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

  19. Preretinal macular fibrosis.

    PubMed

    Mills, P V

    1979-04-01

    The clinical features of preretinal macular fibrosis are reviewed, particular consideration being given to related pathology at the vitreo-retinal interface. These observations are correlated with recent studies of the ultrastructural abnormalities present in this condition. PMID:297382

  20. 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.

  1. 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 BoxCox 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 ?2 tests applying HardyWeinberg 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

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

    PubMed Central

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

    2015-01-01

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

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

    ClinicalTrials.gov

    2015-05-15

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

  4. 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

  5. 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.

  6. 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 ...

  7. Levels of Aqueous Humor Trace Elements in Patients with Non-Exsudative Age-related Macular Degeneration: A Case-control Study

    PubMed Central

    Jnemann, Anselm G. M.; Stopa, Piotr; Michalke, Bernhard; Chaudhri, Anwar; Reulbach, Udo; Huchzermeyer, Cord; Schltzer-Schrehardt, Ursula; Kruse, Friedrich E.; Zrenner, Eberhart; Rejdak, Robert

    2013-01-01

    Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD. For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.96.62, female 8, male 4) and 11 patients without AMD (age 66.616.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards. Patients with AMD had significantly higher aqueous humor levels of cadmium (median: 0.70 mol/L, IQR: 0.400.84 vs. 0.06 mol/L; IQR: 0.01.018; p?=?0.002), cobalt (median: 3.1 mol/L, IQR: 2.623.15 vs. 1.17 mol/L; IQR: 0.951.27; p<0.001), iron (median: 311 mol/L, IQR: 289329 vs. 129 mol/L; IQR: 111145; p<0.001) and zinc (median: 23.1 mol/L, IQR: 12.932.6 vs. 5.1 mol/L; IQR: 4.49.4; p?=?0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 mol/L, IQR: 11.431.3 vs. 49.9 mol/L; IQR: 32.0.142.0; p?=?0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD. Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD. PMID:23457607

  8. 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

  9. 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

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

    PubMed Central

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

    2011-01-01

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

  11. Diabetic Macular Edema

    NASA Astrophysics Data System (ADS)

    Lobo, Conceio; Pires, Isabel; Cunha-Vaz, Jos

    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.

  12. Congenital preretinal macular fibrosis.

    PubMed

    Wise, G N

    1975-03-01

    A 35-year-old woman and a 36-year-old man had asymptomatic, preretinal macular fibrosis involving their left eyes. Both patients were asymptomatic and the lesions were found on routine ocular examination. An opaque gray fibrotic membrane extended toward a lamellar hole in the macular region. Vision, fluorescein angiograms, and Amsler grid testing were normal in both cases. The defect in these two cases possibly arose during early embryonic development and might have been due to a defect produced by adherence of the primary vitreous body to the retina, thus differentiating them from idiopathic preretinal fibrosis, PMID:1121992

  13. VEGF Modulation of Retinal Pigment Epithelium Resistance

    PubMed Central

    Ablonczy, Zsolt; Crosson, Craig E.

    2008-01-01

    Fluid accumulation into the subretinal space and the development of macular edema is a common condition in age-related macular degeneration, diabetic retinopathy, and following ocular surgery, or injury. Vascular endothelial growth factor (VEGF) and other cytokines have been implicated in the disruption of retinal pigment epithelium (RPE) barrier function and a reduction in the regulated removal of subretinal fluid; however, the cellular and molecular events linking these agents to the disruption of barrier function have not been established. In the current study, cultures of ARPE-19 and primary porcine retinal pigment epithelium (RPE) cells were utilized to investigate the effects of the VEGF-induced modifications to the barrier properties of the RPE. The barrier function was determined by transepithelial resistance (TER) measurements and morphology of the RPE monolayers. In both ARPE-19 and primary porcine RPE cells the administration of VEGF produced a significant drop in TER, and this response was only observed following apical administration. Maximum reduction in TER was reached 5 hours post VEGF administration. These responses were concentration-dependent with an EC50 of 502 pg/mL in ARPE-19 cells and 251 pg/mL in primary porcine cells. In both ARPE-19 and primary RPE cells, the response to VEGF was blocked by pretreatment with the relatively selective VEGF-R2 antagonists, SU5416 or ZM323881, or the protein tyrosine kinase inhibitor, genistein. Administration of the relatively selective VEGF-R2 agonist, VEGF-E, also reduced TER in a concentration-dependent manner (EC50 of 474 pg/mL), while VEGF-R1 agonist, placental growth factor (PlGF), did not significantly alter the TER. Immunolocalization studies demonstrated that confluent monolayers exhibited continuous cell-to-cell ZO-1 protein contacts and apical localization of the VEGF-R2 receptors. These data provide evidence that the VEGF-induced breakdown of RPE barrier function is mediated by the activation of apically-oriented VEGF-R2 receptors. Thus, VEGF-mediated increases in RPE permeability are initiated by a rise in intraocular levels of VEGF. PMID:17915218

  14. 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

  15. 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

  16. [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

  17. American Macular Degeneration Foundation

    MedlinePLUS

    ... of Macular Degeneration The Eye as a Camera Anatomy of a Normal Human Eye ADA and Your Legal Protection AMD Treatment ... Amsler Grid Ten Questions to Ask Your Doctor Anatomy of a Normal Human Eye Disclaimer Privacy Policy Americans with Disabilities Act ...

  18. 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 88years 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 12months. 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

  19. Resonance Raman measurement of macular carotenoids in the living human eye.

    PubMed

    Bernstein, Paul S; Zhao, Da-You; Sharifzadeh, Mohsen; Ermakov, Igor V; Gellermann, Werner

    2004-10-15

    There is growing evidence that high levels of the macular xanthophyll carotenoids lutein and zeaxanthin may be protective against visual loss from age-related macular degeneration. To study this protective effect further, it is important to measure macular carotenoid levels noninvasively in a wide variety of subjects. We have developed and validated resonance Raman spectroscopy as a sensitive and specific objective method to measure macular carotenoid levels in the living human eye. In this minireview, the principles and implementation of ocular carotenoid resonance Raman spectroscopy are reviewed, and the results of observational cross-sectional studies and of prospective supplementation studies on subjects with and without macular pathology are summarized. We have recently extended this technology to an imaging mode which will further enhance our understanding of the roles of lutein and zeaxanthin in normal macular function and in the prevention of age-related visual loss. PMID:15369814

  20. 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

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

    PubMed Central

    Pinazo-Durn, Maria D.; Gmez-Ulla, Francisco; Arias, Luis; Araiz, Javier; Casaroli-Marano, Ricardo; Gallego-Pinazo, Roberto; Garca-Medina, Jose J.; Lpez-Glvez, Maria Isabel; Manzanas, Luca; Salas, Anna; Zapata, Miguel; Diaz-Llopis, Manuel; Garca-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 (?-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 ?-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 ?-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 ?-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

  2. 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

  3. 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

  4. 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

  5. '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

  6. Elevated plasma levels of pigment epithelium-derived factor correlated with inflammation and lung function in COPD patients

    PubMed Central

    Li, Xiaoou; Wang, Tao; Yang, Ting; Shen, Yongchun; An, Jing; Liu, Lian; Dong, Jiajia; Guo, Lingli; Li, Diandian; Zhang, Xue; Chen, Lei; Xu, Dan; Wen, Fuqiang

    2015-01-01

    Rationale Pigment epithelium-derived factor (PEDF) is a 50 kD small secreting glycoprotein that participates in multiple physiological and pathological processes. Recent studies have reported that PEDF plays an important role in inflammatory responses in several diseases. However, the role of PEDF in the pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear. Objective The aim of the present study is to explore the potential relationship between PEDF and COPD. Methods We used differential proteomics stable isotope labeling with amino acids in cell culture to investigate protein expression profile changes in cigarette smoke extract-treated pulmonary cells and found that the neurotrophic and antiangiogenic protein PEDF was abnormally expressed. Furthermore, Western blotting was used to detect the expression of PEDF in the lung tissue of rats that were exposed to cigarette smoke. Eighty subjects between the ages of 4090 years, including 20 healthy nonsmokers, ten smoking volunteers, and 50 COPD patients, were recruited from September 2012 until August 2013 in Sichuan Province, Peoples Republic of China. We measured the plasma PEDF concentration and classic proinflammatory cytokines by multiplex enzyme-linked immunosorbent assay. In addition, we performed a spirometry examination to diagnose COPD patients and we also analyzed the correlation between PEDF and lung function. Results First, we found that the expression of PEDF in cigarette smoke extract-treated cells increased 16.2-fold when compared with the control group. Next, we confirmed that 4 weeks exposure to cigarette smoke can upregulate PEDF levels in rat lung tissues. We also discovered that plasma PEDF in COPD patients was significantly increased when compared with either healthy nonsmoking or smoking subjects. Furthermore, circulating PEDF was correlated with inflammatory cytokine and blood neutrophil numbers, but it was reversely associated with a decline in forced expiratory volume in 1 second percent predicted. Conclusion Our findings provide a novel link between PEDF and COPD. Elevated PEDF levels may be involved in promoting the development of COPD by performing proinflamma-tory functions. PMID:25844034

  7. 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

  8. Acute macular edema following intracorporeal prostaglandin injection for erectile dysfunction

    PubMed Central

    Asahi, Masumi G; Chou, Calvin; Gallemore, Ron P

    2015-01-01

    Purpose We aimed to describe the first case of macular edema following intracorporeal injection of alprostadil, a prostaglandin E1. Methods This was a retrospective case report followed with optical coherence tomography, fundus photos, and fluorescein angiography images. Results A patient developed bilateral cystoid macular edema following intracorporeal injection of alprostadil, a prostaglandin E1 for treatment of erectile dysfunction. The edema resolved following treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, with subsequent recovery in visual acuity. Discussion Systemic prostaglandin administration can cause macular edema and vision loss, indicating that elevated systemic prostaglandin levels may affect visual function. This has potential implications for other systemic disorders and treatments that could affect macular function. PMID:26229510

  9. 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

  10. 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

  11. Age-related macular degeneration and the aging eye

    PubMed Central

    Ehrlich, Rita; Harris, Alon; Kheradiya, Nisha S; Winston, Diana M; Ciulla, Thomas A; Wirostko, Barbara

    2008-01-01

    Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruchs membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly. PMID:18982917

  12. 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 ?-melanin-stimulating hormone (?-MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while ?-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

  13. Age-related macular degeneration.

    PubMed Central

    O'Shea, J. G.

    1998-01-01

    Macular degeneration is now responsible for approximately 95% of blindness and partial sighted registrations in the UK. This review has been written specifically to make the general medical community of the UK aware of the prevalence and clinical manifestations of aged-related macular degeneration. The review encompasses the risk factors, the disabilities and problems experienced by suffers of the condition and current therapeutic options. Age related macular degeneration increases in prevalence in our community from 0% among people under 55 years old to 18.5% among those 85 years or older. There is a marked female preponderance. The exudative form of the disorder is commoner. Treatment remains supportive for most patients with macular degeneration although a minority will benefit from macular laser photocoagulation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:9683972

  14. 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

  15. Macular hole formation, progression, and surgical repair: case series of serial optical coherence tomography and time lapse morphing video study

    PubMed Central

    2010-01-01

    Background To use a new medium to dynamically visualize serial optical coherence tomography (OCT) scans in order to illustrate and elucidate the pathogenesis of idiopathic macular hole formation, progression, and surgical closure. Case Presentations Two patients at the onset of symptoms with early stage macular holes and one patient following repair were followed with serial OCTs. Images centered at the fovea and at the same orientation were digitally exported and morphed into an Audiovisual Interleaving (avi) movie format. Morphing videos from serial OCTs allowed the OCTs to be viewed dynamically. The videos supported anterior-posterior vitreofoveal traction as the initial event in macular hole formation. Progression of the macular hole occurred with increased cystic thickening of the fovea without evidence of further vitreofoveal traction. During cyst formation, the macular hole enlarged as the edges of the hole became elevated from the retinal pigment epithelium (RPE) with an increase in subretinal fluid. Surgical repair of a macular hole revealed initial closure of the macular hole with subsequent reabsorption of the sub-retinal fluid and restoration of the foveal contour. Conclusions Morphing videos from serial OCTs are a useful tool and helped illustrate and support anterior-posterior vitreofoveal traction with subsequent retinal hydration as the pathogenesis of idiopathic macular holes. PMID:20849638

  16. Expression of Human Complement Factor H Prevents Age-Related Macular DegenerationLike 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 subretinal 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

  17. 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

  18. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2014-01-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. PMID:25446321

  1. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

    PubMed Central

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

    2014-01-01

    Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

  2. 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

  3. Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina.

    PubMed

    Sparrow, Janet R; Duncker, Tobias; Woods, Russell; Delori, Franois C

    2016-01-01

    Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina. PMID:26427423

  4. 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

  5. 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

  6. 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

  7. Ziv-aflibercept in macular disease

    PubMed Central

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

    2015-01-01

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

  8. High glucose-induced barrier impairment of human retinal pigment epithelium is ameliorated by treatment with Goji berry extracts through modulation of cAMP levels.

    PubMed

    Pavan, Barbara; Capuzzo, Antonio; Forlani, Giuseppe

    2014-03-01

    Human retinal pigment epithelium cells were used to investigate the mechanisms underlying blood-retinal barrier disruption under conditions of chronic hyperglycemia. The treatment with 25mM glucose caused a rapid drop in the transepithelial electrical resistance (TEER), which was reversed by the addition of either a methanolic extract from Goji (Lycium barbarum L.) berries or its main component, taurine. Intracellular cAMP levels increased concurrently with the high glucose-induced TEER decrease, and were correlated to an increased activity of the cytosolic isoform of the enzyme adenylyl cyclase. The treatment with plant extract or taurine restored control levels. Data are discussed in view of a possible prevention approach for diabetic retinopathy. PMID:24345371

  9. 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 ...

  10. 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

  11. What Is Age-Related Macular Degeneration?

    MedlinePLUS

    ... D. Español Eye Health / Eye Health A-Z Age-Related Macular Degeneration Sections What Is Age-Related ... Age-Related Macular Degeneration Vision Simulator What Is Age-Related Macular Degeneration? Written by: Kierstan Boyd Reviewed ...

  12. Systemic and Ocular Long Pentraxin 3 in Patients with Age-Related Macular Degeneration

    PubMed Central

    Munthe-Fog, Lea; Bastrup-Birk, Simone; Reese-Petersen, Alexander Lynge; Falk, Mads Krger; Singh, Amardeep; Srensen, Torben Lykke; Garred, Peter; Nissen, Mogens Holst

    2015-01-01

    Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One of the ligands for CFH is long pentraxin 3 (PTX3), which is produced locally in the retinal pigment epithelium (RPE). To test the hypothesis that PTX3 is relevant to retinal immunohomeostasis and may be associated with AMD pathogenesis, we measured plasma PTX3 protein concentration and analyzed the RPE/choroid PTX3 gene expression in patients with AMD. To measure the ability of RPE cells to secrete PTX3 in vitro, polarized ARPE-19 cells were treated with activated T cells or cytokines (interferon (IFN)-gamma and/or tumor necrosis factor (TNF)-alpha) from the basolateral side; then PTX3 protein concentration in supernatants and PTX3 gene expression in tissue lysates were quantified. Plasma levels of PTX3 were generally low and did not significantly differ between patients and controls (P=0.307). No statistically significant difference was observed between dry and exudative AMD nor was there any correlation with hsCRP or CFH genotype. The gene expression of PTX3 increased in RPE/choroid with age (P=0.0098 macular; P=0.003 extramacular), but did not differ between aged controls and AMD patients. In vitro, ARPE-19 cells increased expression of the PTX3 gene as well PTX3 apical secretions after stimulation with TNF-alpha or activated T cells (P<0.01). These findings indicate that PTX3 expressed in the eye cannot be detected systemically and systemic PTX3 may have little or no impact on disease progression, but our findings do not exclude that locally produced PTX3 produced in the posterior segment of the eye may be part of the AMD immunopathogenesis. PMID:26176960

  13. L-cone pigment genes expressed in normal colour vision.

    PubMed

    Sjoberg, S A; Neitz, M; Balding, S D; Neitz, J

    1998-11-01

    To directly test the hypothesis that only two pigment genes are expressed from the X-chromosome array, we examined expressed M and L pigment gene sequences from > 100 male eye donors. In this sample, there were eight men who expressed high levels of more than one L pigment gene in addition to M pigment genes. The fact that these eyes expressed both L and M pigment genes at significant levels suggests they were from men with normal colour vision. We reject the hypothesis that only two pigment genes from one X-chromosome array can be expressed. PMID:9893828

  14. 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].

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Diabetic macular edema.

    PubMed

    Stefnsson, Einar

    2009-07-01

    A variety of treatment options are available for the treatment of diabetic macular edema. They include laser photocoagulation, anti-VEGF drugs, intravitreal steroids, and vitrectomy with or without release of vitreoretinal traction. A full understanding of the physiological mechanisms of these treatment modalities allows sensible combination of treatment options. Retinal photocoagulation has repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen naturally reduces VEGF production and thereby decreases leakage of plasma proteins from capillaries into the tissue. In addition, vitrectomy allows faster clearance of cytokines, such as VEGF, from the retina into the vitreous cavity. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and corticosteroids reduce the effect of VEGF on capillary permeability. Starling's law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains how VEGF-induced vascular permeability causes plasma protein to leak into the tissue interstitial space, thus decreasing the osmotic pressure gradient between vessel and tissue, resulting in water accumulation, i.e. edema. This is reversed by reducing VEGF production, which is achieved with laser treatment; or by removing VEGF with antibodies or vitrectomy; or by reducing the permeability effect with steroids. At the same time, Starling's law takes into account hemodynamic changes that affect the hydrostatic gradient. High arterial blood pressure and hypoxic vasodilatation increase the hydrostatic pressure in the microcirculation, which increases water flux from vessel to tissue and induce edema. Treatment of arterial hypertension or reversal of retinal hypoxia with laser reverses this pathophysiology and reduces edema. Newton's third law explains, that vitreoretinal traction decreases hydrostatic tissue pressure in the retina, increases the pressure gradient between vessel and tissue, and stimulates water fluxes from vessel into tissue, leading to edema. Release of vitreoretinal traction reverses this mechanism and reduces edema. PMID:23960851

  20. 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.; DAmato, 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 Bruchs 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 ?-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 Bruchs membrane. These results support the hypothesis that additional insults to the integrity of Bruchs 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

  1. 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

  2. Skin Pigmentation Disorders

    MedlinePLUS

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

  3. Pigmented Lesions of the Retinal Pigment Epithelium.

    PubMed

    Ly, Angelica; Nivison-Smith, Lisa; Hennessy, Michael; Kalloniatis, Michael

    2015-08-01

    : The primary eye care practitioner assumes an important role in clinical decisions involving the differentiation between malignant and nonmalignant pigmented lesions. A misdiagnosis may have profound consequences on patient management and visual or life prognosis. However, information on these lesions, particularly their appearance using advanced imaging, is fragmented throughout the literature. The purpose of this review is to describe these features in detail, so that the implications of this information on clinical practice are more readily apparent. Clinically relevant descriptions of pigmented lesions of the retinal pigment epithelium using traditional and advanced imaging modalities in the literature were collated and integrated with findings from patients seen at the Centre for Eye Health. The information was then organized and tabulated. Finally, a flow diagram was created to be used as a clinical reference in the differential diagnosis of pigmented lesions of the retinal pigment epithelium. PMID:26099061

  4. Pigmented Bowen's disease.

    PubMed

    Mota, Amanda Nascimento Cavalleiro de Macedo; Pieiro-Maceira, Juan; Alves, Maria de Fatima Guimares Scotelaro; Tarazona, Mnica Jidid Mateus

    2014-01-01

    Pigmented Bowen's disease is rare, though more prevalent in men. It presents as a well-delineated plaque in areas unexposed to sun. There are reports of association with seborrheic keratosis, solar lentigo or exuberant pigmentation of genital and intertriginous regions. A specific dermoscopy finding is the presence of brown or gray dots in regular arrangement and coiled or dotted vessels. Thus, we aim to raise awareness of the diagnosis of pigmented Bowen's disease in pigmented lesions. PMID:25184929

  5. 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

  6. 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

  7. 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...

  8. 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

  9. 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

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

    PubMed Central

    Willermain, Franois; 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-06-01

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

    PubMed

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

    2015-01-01

    Excessive visible light exposure can induce damage to retinal cells and contribute to the development or progression of age-related macular degeneration. In this study we created a model of phototoxicity in pigmented rabbits. Furthermore, we investigated the protective effect of bilberry anthocyanin extract (BAE, Table A1) and explored the possible mechanisms of action in this model. The model of light-induced retinal damage was established by the pigmented rabbits exposed to light at 18,000 lx for 2 h, and they were sacrificed on day 7. After administration of BAE at dosages of 250 and 500 mg/kg/day, retinal dysfunction was significantly inhibited in terms of electroretinograms, and the decreased thicknesses of retinal outer nuclear layer and lengths of the outer segments of the photoreceptor cells were suppressed in rabbits with retinal degeneration. BAE attenuated the changes caused by light to certain apoptotic proteins (Bax, Bcl-2, and caspase-3). The extract increased the levels of superoxide dismutase, glutathione peroxidase, and catalase, as well as the total antioxidant capacity, but decreased the malondialdehyde level in the retinal cells. BAE inhibited the light-induced elevation in the levels of proinflammatory cytokines and angiogenic parameters (IL-1? and VEGF). Results showed that visible light-induced retinal degeneration model in pigmented rabbits was successfully established and BAE exhibited protective effects by increasing the antioxidant defense mechanisms, suppressing lipid peroxidation and proinflammatory cytokines, and inhibiting retinal cells apoptosis. PMID:26694327

  14. ‘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

  15. 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.

  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. Identification of spectral phenotypes in age-related macular degeneration patients

    NASA Astrophysics Data System (ADS)

    Davis, Bert; Russell, Steven; Abramoff, Michael; Nemeth, Sheila C.; Barriga, E. Simon; Soliz, Peter

    2007-02-01

    The purpose of this study is to show that there exists a spectral characteristic that differentiates normal macular tissue from various types of genetic-based macular diseases. This paper demonstrates statistically that hyperspectral images of macular and other retinal tissue can be used to spectrally differentiate different forms of age-related macular degeneration. A hyperspectral fundus imaging device has been developed and tested for the purpose of collecting hyperspectral images of the human retina. A methodology based on partial least squares and ANOVA has been applied to determine the hyperspectral representation of individual spectral characteristics of retinal features. Each discrete tissue type in the retina has an identifiable spectral shape or signature which, when combined with spatial context, aids in detection of pathological features. Variations in the amount and distribution of various ocular pigments or the inclusion of additional biochemical substances will allow detection of pathological conditions prior to traditional histological presentation. Fundus imaging cameras are ubiquitous and are one of the most common imaging modalities used in documenting a patient's retinal state for diagnosis, e.g. remotely, or for monitoring the progression of an ocular disease. The added diagnostic information obtained with only a minor retro-fit of a specialized spectral camera will lead to new diagnostic information to the clinical ophthalmologist or eye-care specialist.

  18. 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??mol/L). An arginine-restricted diet reduced serum ornithine level (55??mol/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.

  19. Zinc Deficiency Leads to Lipofuscin Accumulation in the Retinal Pigment Epithelium of Pigmented Rats

    PubMed Central

    Kokkinou, Despina; Eibl, Oliver; Schraermeyer, Ulrich

    2011-01-01

    Background Age-related macular degeneration (AMD) is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. Methodology/Principal Findings Adult Long Evans (LE) rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE) were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX) microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE). The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (>3 m) found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 m were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.43 m and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it. Conclusions/Significance In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane. PMID:22216222

  20. 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

  1. 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.

  2. 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

  3. Pigment gene expression in protan color vision defects.

    PubMed

    Balding, S D; Sjoberg, S A; Neitz, J; Neitz, M

    1998-11-01

    We screened 150 male eye donors and identified four who did not have or express L pigment genes, consistent with each of them having a congenital protan color vision defect. One donor was identified as a protanope because he had and expressed a single X-chromosome photopigment gene that encoded an M pigment. Three were categorized as protanomalous because each expressed significant levels of genes specifying two spectrally different M pigments. The first gene in each of the protanomalous arrays was expressed the most and encoded an M pigment that differed in amino acid sequence from M pigments in color normal men. PMID:9893849

  4. 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

  5. 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

  6. 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

  7. Age-related macular degeneration

    PubMed Central

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

    2011-01-01

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

  8. Gene therapy in age related macular degeneration and hereditary macular disorders.

    PubMed

    Kinnunen, Kati; Yla-Herttuala, Seppo

    2012-01-01

    In ophthalmology, administration of the therapeutic agent can be difficult due to the tight barriers in the eye. Multiple injections may be needed to allow the therapeutic agent to reach adequate levels in retina and choroidea which may increase the risk of complications including endophthalmitis, cataract and haemorrhages. Optimal methods for the delivery of therapeutic agents to the posterior segments of the eye have not yet been developed. Gene therapy offers an alternative where the therapeutic protein or proteins can be induced in the target tissue for a prolonged period of time after a single injection. The eye is a promising target for gene therapy due to its small size and tissue boundaries preventing leakage of the therapeutic material to other tissues or systemic circulation. However, most of the work in ocular gene therapy is still at the preclinical phase; only three vectors have reached phase 1/2 clinical trials. This review summarizes basic principles and current status of gene therapy in age related macular degeneration and hereditary macular disorders. PMID:22652660

  9. Congenital high myopia and central macular atrophy; a report of 3 families

    PubMed Central

    Hull, Sarah; Kalhoro, Ambreen; Marr, Jane; Thompson, Dorothy A; Holder, Graham E; Robson, Anthony G; Moore, Anthony T

    2015-01-01

    Aims To report the clinical phenotype in a series of 4 children from 3 families with the rare association of high myopia, central macular atrophy and normal full-field electroretinography (ERG). Methods Four male patients were ascertained with reduced vision, nystagmus and atrophy of the macula from early childhood. Patients underwent full ophthalmic examination, electrophysiological testing and retinal imaging. Results Minimum duration of follow up was 8 years. At last review, visual acuity ranged from 0.22 to 1.20 logMAR (6/9.5-6/95 Snellen) at a mean age of 10.5 years (median 9.5 years, range 9-14 years). Refractive error ranged from a spherical equivalent of ?7.40 D to ?24.00 D. Three had convergent squint. Fundus examination and imaging demonstrated bilateral macular atrophy in all patients, which varied from mild atrophy of the retinal pigment epithelium (RPE) to well demarcated, punched out atrophic lesions of retina, RPE and choroid. Flash ERG was normal under photopic and scotopic conditions in all patients. Pattern ERG, performed in 3 patients, was consistent with mild to severe macular dysfunction. Progression of the area of atrophy was evident in 1 patient and of the myopia in 2 patients but all patients had stable visual acuity. Conclusions Patients with congenital high myopia and macular atrophy present in infancy with reduced visual acuity and nystagmus. The macular atrophic lesions vary in size and severity but electrophysiological testing is consistent with dysfunction confined to the macula. There was no deterioration in visual acuity over 8-10 years of monitoring. PMID:25998941

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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, Bruchs 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

  15. [Etiopathogenesis in macular edema and therapeutic approach].

    PubMed

    Buliga, Simona

    2011-01-01

    Macular edema is one of the most frequent cause of low vision with very different causes. It is a non-specific response to the change in the permeability of blood-ocular barrier. The tendency of the retina to form cistoid macular edema is little understood. There are situations where it is associated with leakage of the small perifoveolar capillaries as there are situations, such as diabetic macular edema, where the leakage is a diffuse thickening of the posterior pole with or without cistoid changes in macula. PMID:22642133

  16. Advances in the management of macular degeneration

    PubMed Central

    2014-01-01

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

  17. Peripheral retinal angiomalike lesion and macular pucker.

    PubMed

    Laatikainen, L; Immonen, I; Summanen, P

    1989-11-15

    We interpreted clinical data on five eyes with preretinal macular fibrosis (macular pucker) in association with a solitary angiomalike lesion in the peripheral retina. One angioma was associated with von Hippel-Lindau disease, and the others were regarded as acquired sporadic angiomas occurring in otherwise healthy persons. Regression of the vascular mass occurred as a result of transscleral cryopexy in four eyes and by argon laser in one eye. After treatment, the macular pucker was stabilized, but regression of the preretinal membrane did not occur. The visual acuity improved after cryotherapy in one eye, and in two eyes visual improvement occurred after vitrectomy and membrane removal. PMID:2817054

  18. 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

  19. 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

  20. Parkinson's Drug Shows Promise Against Macular Degeneration

    MedlinePLUS

    ... nih.gov/medlineplus/news/fullstory_155695.html Parkinson's Drug Shows Promise Against Macular Degeneration But more research ... no one is recommending that patients take the drug, levodopa (L-dopa), to thwart eye disease. But ...

  1. Risk of bilateral idiopathic preretinal macular fibrosis.

    PubMed

    Hikichi, T; Trempe, C L

    1995-01-01

    To ascertain the risk of the development of bilateral idiopathic preretinal macular fibrosis, we retrospectively studied 380 consecutive patients with idiopathic preretinal macular fibrosis. Eighty (21%) patients had bilateral involvement. Sixteen (39%) of 41 patients with diabetes, 40 (28%) of 144 with hypertension, and 12 of 21 (57%) with bilateral high myopia had bilateral involvement. The prevalence of bilateral involvement was significantly higher in patients with these three pathologies than in patients without these conditions (p < 0.01, p < 0.02 and p < 0.01, respectively). In patients with diabetes or hypertension, no significant difference was found in the prevalence of posterior vitreous detachment (PVD) between involved or uninvolved eyes. Diabetes, hypertension even without retinopathy, and high myopia may be risk factors for bilateral involvement of idiopathic preretinal macular fibrosis. Factors other than PVD may be involved in the development of idiopathic preretinal macular fibrosis in patients with diabetes or hypertension. PMID:7713252

  2. Genetics Home Reference: Vitelliform macular dystrophy

    MedlinePLUS

    ... Resources - National Institutes of Health National Eye Institute: Diagram of the Eye Educational resources - Information pages (3 ... Families Resources for Health Professionals What glossary definitions help with understanding vitelliform macular dystrophy? autosomal ; autosomal dominant ; ...

  3. Age-Related Macular Degeneration (AMD)

    MedlinePLUS

    ... Research at NEI Education Programs Training and Jobs Age-Related Macular Degeneration (AMD) Listen AMD Defined AMD ... of Cases between 2000 and 2010 2010 U.S. Age-Specific Prevalence Rates for AMD by Age and ...

  4. 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

  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. Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?

    PubMed

    Qi, Miao; Abdelatti, Mahmoud; Krilis, Matthew; Madigan, Michele C; Weaver, James; Guymer, Robyn H; McCluskey, Peter; Wang, Ying; Zhou, Saijun; Krilis, Steven A; Giannakopoulos, Bill

    2016-01-01

    Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (?2GPI) in the plasma of individuals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of ?2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H2O2)-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate ?2GPI in the retina and choroid of patients with AMD. Free thiol ?2GPI is shown to protect the immortalized human RPE cell line against H2O2-induced cell death, whereas the oxidized form of ?2GPI and free thiol bovine serum albumin were not protective. Free thiol ?2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol ?2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD. Antioxid. Redox Signal. 24, 32-38. PMID:25827171

  8. Intracellular pigment epithelium-derived factor contributes to triglyceride degradation.

    PubMed

    Dai, Zhiyu; Zhou, Ti; Li, Cen; Qi, Weiwei; Mao, Yuling; Lu, Juling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Cai, Weibin; Yang, Zhonghan; Ma, Jianxing; Yang, Xia; Gao, Guoquan

    2013-09-01

    Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity. PMID:23886488

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

    PubMed

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

    2016-01-01

    Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy. PMID:26212151

  10. Pigmented epidermal cysts.

    PubMed

    Shet, T; Desai, S

    2001-10-01

    There are few reports documenting the presence of melanin or melanocytes in epidermal cysts. One hundred and twenty five epidermal cysts from Indian patients were analyzed for the presence of melanin pigment and their sites were noted. A Masson's Fontana stain and immunohistochemistry for S-100 protein and HMB 45 was performed for localization of melanin and melanocytes within the epidermal cysts. Seventy-nine (63%) of the epidermal cysts showed presence of melanin pigment or melanocytes to a variable extent. Melanin was not present in epidermal cysts occurring along lines of fusion of skin folds during embryonogenesis (e.g., ventral midline, inner canthus, nose, upper lip and in the distal most parts like leg and foot and also scrotum). Ten of the 79 epidermal cysts showed extensive accumulation of melanin pigment and infiltration with melanophages in the cyst wall. Four of these patients gave history of trauma and the follow-up was uneventful in two of them. Pigmentation of epidermal cysts thus follows a definite anatomic pattern and is dependent on the natural skin color. Large amount of pigment accumulation within epidermal cysts occurs after cyst rupture and is not associated with hemochromatosis as was believed in the past. PMID:11801783

  11. 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

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

    PubMed Central

    Nita, Ma?gorzata; Strza?ka-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 Bruchs 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 20052012, using the following keywords: AMD, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases, Bruchs 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

  13. The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity.

    PubMed

    Kent, D

    2015-11-01

    This review summarises our current understanding of the molecular basis of subretinal neovascularisation (SRNV) in age-related macular degeneration (AMD). The term neovascular AMD (NVAMD) is derived from the dominant early clinical features of haemorrhage, fluid, and lipid in the subretinal space (SRS) and the historical role of fluorescein angiography in detecting the presence of NV tissue. However, at the cellular level, SRNV resembles an aberrant but stereotypical tissue repair response that incorporates both an early inflammatory phase and a late fibrotic phase in addition to the neovascular (NV) component that dominates the early clinical presentation. This review will seek not only to highlight the important molecules involved in each of these components but to demonstrate that the development of SRNV has its origins in the earliest events in non-NV AMD pathogenesis. Current evidence suggests that this early-stage pathogenesis is characterised by complement-mediated immune dysregulation, leading to a state of chronic inflammation in the retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. These initial events can be seamlessly and inextricably linked to late-stage development of SRNV in AMD by the process of dynamic reciprocity (DyR), the ongoing bidirectional communication between cells, and their surrounding matrix. Moreover, this correlation between disease onset and eventual outcome is reflected in the temporal and spatial correlation between chronic inflammation, NV, and fibrosis within the reparative microenvironment of the SRS. In summary, the downstream consequences of the earliest dysfunctional molecular events in AMD can result in the late-stage entity we recognize clinically as SRNV and is characterized by a spectrum of predictable, related, and stereotypical processes referred to as DyR. PMID:26228288

  14. 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 Bruchs 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 Bruchs membrane lipoprotein binding and show, using human Bruchs 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

  15. 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

  16. 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.

  17. Identification of lesion components that influence visual function in age related macular degeneration

    PubMed Central

    Hogg, R; Curry, E; Muldrew, A; Winder, J; Stevenson, M; McClure, M; Chakravarthy, U

    2003-01-01

    Aims: To explore the relation between lesion composition as assessed by fundus photography and fluorescein angiography with clinical measures of vision in eyes of patients with age related macular degeneration (AMD). Methods: A standardised visual function assessment along with colour stereo pair fundus photography was carried out in both eyes of 58 subjects with a confirmed clinical diagnosis of AMD. The size, location, and composition of the macular lesion (blood, exudate, subretinal fluid, pigment, membrane, atrophy, and fibrosis) were measured on the colour photographs using computer assisted image analysis. Of the 58 subjects, 44 also had concurrent fluorescein angiography. Classic and occult choroidal neovascularisation (CNV), blood, blocked fluorescence, fibrosis, geographic atrophy, and the total area of abnormal fluorescence were measured. Multiple linear regression was used to examine the relation between clinical measures of vision and the location and extent of lesion components identified by both colour and fluorescein image capture. Results: The composition of the macular lesion strongly influenced visual function, with atrophy (p=0.001) and fibrosis (p=0.002) accounting for most of the variation. When the location of the lesion with respect to the fovea was examined, fibrosis within the fovea significantly influenced all clinical measures of vision (p=0.008). The regression model selected the total area of abnormal fluorescence and a composite parameter (a semiquantitative measure of the following characteristics: atrophy, exudates, blood, and fibrosis ) from colour photography (r2 =0.52) as the variables that explained most of the variation in clinical measures of vision. Conclusions: The composition and extent of the macular lesion strongly influences visual function in eyes with AMD. Both colour photography and angiography yielded information, which together explained considerably more of the variation in the clinical measures of vision than either on its own. PMID:12714405

  18. Familial grouped pigmentation of the retinal pigment epithelium.

    PubMed Central

    de Jong, P T; Delleman, J W

    1988-01-01

    Grouped pigmentation of the retinal pigment epithelium was found in a father and his son. They had a normal resting potential on the electro-oculogram, but the son had a lower normal light rise. We believe this is the first description of familial grouped pigmentation. Images PMID:3390419

  19. 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

  20. 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

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

    PubMed

    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-1?, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1? causes enhanced cell death. Furthermore, IL-1? 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

  2. 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.

  3. Evidence for Baseline Retinal Pigment Epithelium Pathology in the Trp1-Cre Mouse

    PubMed Central

    Thanos, Aristomenis; Morizane, Yuki; Murakami, Yusuke; Giani, Andrea; Mantopoulos, Dimosthenis; Kayama, Maki; Roh, Mi In; Michaud, Norman; Pawlyk, Basil; Sandberg, Michael; Young, Lucy H.; Miller, Joan W.; Vavvas, Demetrios G.

    2012-01-01

    The increasing popularity of the Cre/loxP recombination system has led to the generation of numerous transgenic mouse lines in which Cre recombinase is expressed under the control of organ- or cell-specific promoters. Alterations in retinal pigment epithelium (RPE), a multifunctional cell monolayer that separates the retinal photoreceptors from the choroid, are prevalent in the pathogenesis of a number of ocular disorders, including age-related macular degeneration. To date, six transgenic mouse lines have been developed that target Cre to the RPE under the control of various gene promoters. However, multiple lines of evidence indicate that high levels of Cre expression can be toxic to mammalian cells. In this study, we report that in the Trp1-Cre mouse, a commonly used transgenic Cre strain for RPE gene function studies, Cre recombinase expression alone leads to RPE dysfunction and concomitant disorganization of RPE layer morphology, large areas of RPE atrophy, retinal photoreceptor dysfunction, and microglial cell activation in the affected areas. The phenotype described herein is similar to previously published reports of conditional gene knockouts that used the Trp1-Cre mouse, suggesting that Cre toxicity alone could account for some of the reported phenotypes and highlighting the importance of the inclusion of Cre-expressing mice as controls in conditional gene targeting studies. PMID:22429967

  4. 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

  5. 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

  6. 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…

  7. 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.

  8. [Hemosiderin pigmentation in Sezry's syndrome].

    PubMed

    Hundeiker, M; Lffler, H

    1976-10-01

    A 75 year old woman suffering from Sezary syndrome with edemas and excessive pigmentations is presented. In previous observations, pigmentation was caused by melanosis. In our patient it is caused by hemosiderosis. The origin of the pigmentation by a purpura-pigmentosa-progressiva-like mechanism or by the tumor disease itself is discussed. PMID:136428

  9. Macular degeneration in an arc welder.

    PubMed

    Kim, Eun A; Kim, Byung-Gyu; Yi, Cheol-Ho; Kim, Il Gon; Chae, Chang-Ho; Kang, Seong-Kyu

    2007-04-01

    A male welder who had been working in an industrial machine plant for more than 20 years experienced acute intense pain in his left eye with continuous lacrimation while performing arc welding in 1997. Later in 1997, at the age of 39 yr, macular edema was found in his left eye. He was diagnosed with macular degeneration (MD) of the left eye in 2002, and with right eye MD in 2004. Radiation in the visible and near infrared (IR) spectra penetrates the eye and is absorbed by the retina, possibly causing thermal or photochemical damage. Such retinal damage may be permanent and, therefore, sight-threatening. The young age and history of an acute painful eye injury are not consistent with age related macular degeneration (AMD) but rather is likely maculopathy caused by welding arc exposure. PMID:17485886

  10. [Doyne-type honeycombed macular degeneration].

    PubMed

    Isp??oiu, C; Iliu?, C

    1995-01-01

    The case of a 52-year-old patient, who presents since his youth round areas, white to yellow, sometimes confluent, having an aspect of mosaic, in the macular, papillary and intermaculopapillary regions, is examined. In the macular region of the left eye a red macular area has an aspect of pseudohole. The visual acuity is good, with image distortion at proximity. Central little scotomas can be seen, the computerized perimetry also reveals the diminish of the visual capacity at 802 (RE) and 785 (LE). The adaptometry is slightly diminished, there is also a unsystematic dyschromatopsia at pseudo-iso-chromatic tables. Angiographically there is a hyperfluorescence with overlaps on the ophthalmoscopical yellow-white areas. The lesions are interpreted as Doyne degenerescence, due to mucopolyzaharide deposits in the cuticular layer of Bruch membrane. The particularity of the case consist of a good conservation of visual function, compared to ophthalmoscopic lesions. PMID:7654678

  11. 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

  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. 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

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

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

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

  15. Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in the retinal pigment epithelium.

    PubMed

    Toops, Kimberly A; Tan, Li Xuan; Jiang, Zhichun; Radu, Roxana A; Lakkaraju, Aparna

    2015-01-01

    Autophagy is an essential mechanism for clearing damaged organelles and proteins within the cell. As with neurodegenerative diseases, dysfunctional autophagy could contribute to blinding diseases such as macular degeneration. However, precisely how inefficient autophagy promotes retinal damage is unclear. In this study, we investigate innate mechanisms that modulate autophagy in the retinal pigment epithelium (RPE), a key site of insult in macular degeneration. High-speed live imaging of polarized adult primary RPE cells and data from a mouse model of early-onset macular degeneration identify a mechanism by which lipofuscin bisretinoids, visual cycle metabolites that progressively accumulate in the RPE, disrupt autophagy. We demonstrate that bisretinoids trap cholesterol and bis(monoacylglycero)phosphate, an acid sphingomyelinase (ASMase) cofactor, within the RPE. ASMase activation increases cellular ceramide, which promotes tubulin acetylation on stabilized microtubules. Live-imaging data show that autophagosome traffic and autophagic flux are inhibited in RPE with acetylated microtubules. Drugs that remove excess cholesterol or inhibit ASMase reverse this cascade of events and restore autophagosome motility and autophagic flux in the RPE. Because accumulation of lipofuscin bisretinoids and abnormal cholesterol homeostasis are implicated in macular degeneration, our studies suggest that ASMase could be a potential therapeutic target to ensure the efficient autophagy that maintains RPE health. PMID:25378587

  16. Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in the retinal pigment epithelium

    PubMed Central

    Toops, Kimberly A.; Tan, Li Xuan; Jiang, Zhichun; Radu, Roxana A.; Lakkaraju, Aparna

    2015-01-01

    Autophagy is an essential mechanism for clearing damaged organelles and proteins within the cell. As with neurodegenerative diseases, dysfunctional autophagy could contribute to blinding diseases such as macular degeneration. However, precisely how inefficient autophagy promotes retinal damage is unclear. In this study, we investigate innate mechanisms that modulate autophagy in the retinal pigment epithelium (RPE), a key site of insult in macular degeneration. High-speed live imaging of polarized adult primary RPE cells and data from a mouse model of early-onset macular degeneration identify a mechanism by which lipofuscin bisretinoids, visual cycle metabolites that progressively accumulate in the RPE, disrupt autophagy. We demonstrate that bisretinoids trap cholesterol and bis(monoacylglycero)phosphate, an acid sphingomyelinase (ASMase) cofactor, within the RPE. ASMase activation increases cellular ceramide, which promotes tubulin acetylation on stabilized microtubules. Live-imaging data show that autophagosome traffic and autophagic flux are inhibited in RPE with acetylated microtubules. Drugs that remove excess cholesterol or inhibit ASMase reverse this cascade of events and restore autophagosome motility and autophagic flux in the RPE. Because accumulation of lipofuscin bisretinoids and abnormal cholesterol homeostasis are implicated in macular degeneration, our studies suggest that ASMase could be a potential therapeutic target to ensure the efficient autophagy that maintains RPE health. PMID:25378587

  17. 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

  18. Macular abnormalities in the reattached retina.

    PubMed Central

    Cleary, P E; Leaver, P K

    1978-01-01

    Sixty-six patients in whom the macula was detached before surgery were observed for at least 1 year after retinal reattachment. Macular abnormalities were recognised clinically in most patients with severely reduced vision. Failure of retinal receptor regeneration or receptor misalignment may account for visual reduction in a minority of patients but may be less important as a cause of reduced visual acuity than was previously supposed. This study confirms that the visual prognosis is related to the duration of the detachment before surgery, and patients with a macular detachment for 2 months or longer are likely to suffer persistently reduced vision. Images PMID:708677

  19. Macular bioaccelerometers on earth and in space

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

    Spaceflight offers the unique opportunity to study linear bioaccelerometers (vestibular maculas) in the virtual absence of a primary stimulus, gravitational acceleration. 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, three-dimensional reconstructions 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.

  20. An unusual presentation of macular amyloidosis.

    PubMed

    Melo, Brbara Lima Arajo; Costa, Igor Santos; Goes, Clara de Assis Martins; Tigre, Celina Aguiar Frota; Andr, Nara Frota

    2011-01-01

    Macular amyloidosis is a form of cutaneous amyloidosis characterized by dusky-brown lesions usually located on the upper back between the shoulder blades. This report describes the case of a 45 year-old female presenting with hyperpigmented macules and lace-like, non-pruritic erythema in the sacral and cervical region as well as on both arms and legs. Histology revealed amyloid deposits in the papillary dermis which exhibited apple-green birefringence after Congo red staining. There were no systemic findings. This is a case of macular amyloidosis with an unusual presentation. The literature on the subject is also reviewed. PMID:22068763

  1. 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.

  2. Vitrectomy in eyes at risk for macular hole formation.

    PubMed

    Jost, B F; Hutton, W L; Fuller, D G; Vaiser, A; Snyder, W B; Fish, G E; Spencer, R; Birch, D G

    1990-07-01

    Fifteen eyes believed to be at increased risk for macular hole formation underwent vitrectomy in an attempt to prevent macular hole formation. Full-thickness macular holes have not developed in 10 of 11 eyes with stage 1 macular holes. Four eyes were noted to have small full-thickness foveal defects (stage 2 macular holes) at the time of vitrectomy. Two of the four eyes have not progressed to macular hole formation and have 20/25 visual acuity. All patients have been followed for a minimum of 13 months (median, 18 months). The 12 eyes that have not experienced macular hole formation have had a significant (P less than 0.001) improvement in vision with seven (58%) attaining visual acuity of 20/25 or better. The postoperative foveal electroretinogram (ERG) amplitude was higher than the preoperative amplitude in five of the six eyes tested. PMID:2381695

  3. 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

  4. Serous macular detachment, yellow macular deposits, and prominent middle limiting membrane in multiple myeloma.

    PubMed

    Dogan, Berna; Erol, Muhammet Kazim; Toslak, Devrim; Coban, Deniz Turgut; Bulut, Mehmet; Cengiz, Ayse; Sari, Esin Sogutlu

    2015-01-01

    Bone marrow-derived multiple myeloma is a type of plasma cell tumor that may be associated with ocular complications. A 52-year-old male patient was admitted to our eye clinic with the complaint of sudden visual loss and a visual acuity of 20/50 in the right eye and 20/800 in the left eye. Fundus examination revealed common flame-shaped hemorrhages, venous dilatation and tortuosity, Roth spots, serous macular detachment, and yellow macular deposits in both eyes. Evaluation with fundus fluorescein angiography, fundus autofluorescence, and spectral-domain optical coherence tomography resulted in suspicion of hyperviscosity retinopathy and referral to the hematology clinic. After hematology consultation confirmed a diagnosis of multiple myeloma, chemotherapy and plasmapheresis were initiated. Four months after presentation, best-corrected visual acuity was 20/20 in both eyes and improvement in hyperviscosity retinopathy, serous macular detachment, and yellow macular deposits was observed. PMID:25995641

  5. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... astaxanthin level. (2) Color additive mixtures for fish feed use made with paracoccus pigment may contain only... additive is used to enhance the pink to orange-red color of the flesh of salmonid fish. (2) The quantity of... section. (2) The presence of the color additive in finished fish feed prepared according to paragraph...

  6. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... astaxanthin level. (2) Color additive mixtures for fish feed use made with paracoccus pigment may contain only... additive is used to enhance the pink to orange-red color of the flesh of salmonid fish. (2) The quantity of... section. (2) The presence of the color additive in finished fish feed prepared according to paragraph...

  7. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... astaxanthin level. (2) Color additive mixtures for fish feed use made with paracoccus pigment may contain only... additive is used to enhance the pink to orange-red color of the flesh of salmonid fish. (2) The quantity of... section. (2) The presence of the color additive in finished fish feed prepared according to paragraph...

  8. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... astaxanthin level. (2) Color additive mixtures for fish feed use made with paracoccus pigment may contain only... additive is used to enhance the pink to orange-red color of the flesh of salmonid fish. (2) The quantity of... section. (2) The presence of the color additive in finished fish feed prepared according to paragraph...

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

    SciTech Connect

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

    1994-09-01

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

  10. AlphaB-crystallin is found in detergent-resistant membrane microdomains and is secreted via exosomes from human retinal pigment epithelial cells.

    PubMed

    Gangalum, Rajendra K; Atanasov, Ivo C; Zhou, Z Hong; Bhat, Suraj P

    2011-02-01

    ?B-crystallin (?B) is known as an intracellular Golgi membrane-associated small heat shock protein. Elevated levels of this protein have been linked with a myriad of neurodegenerative pathologies including Alzheimer disease, multiple sclerosis, and age-related macular degeneration. The membrane association of ?B has been known for more than 3 decades, yet its physiological import has remained unexplained. In this investigation we show that ?B is secreted from human adult retinal pigment epithelial cells via microvesicles (exosomes), independent of the endoplasmic reticulum-Golgi protein export pathway. The presence of ?B in these lipoprotein structures was confirmed by its susceptibility to digestion by proteinase K only when exosomes were exposed to Triton X-100. Transmission electron microscopy was used to localize ?B in immunogold-labeled intact and permeabilized microvesicles. The saucer-shaped exosomes, with a median diameter of 100-200 nm, were characterized by the presence of flotillin-1, ?-enolase, and Hsp70, the same proteins that associate with detergent-resistant membrane microdomains (DRMs), which are known to be involved in their biogenesis. Notably, using polarized adult retinal pigment epithelial cells, we show that the secretion of ?B is predominantly apical. Using OptiPrep gradients we demonstrate that ?B resides in the DRM fraction. The secretion of ?B is inhibited by the cholesterol-depleting drug, methyl ?-cyclodextrin, suggesting that the physiological function of this protein and the regulation of its export through exosomes may reside in its association with DRMs/lipid rafts. PMID:21097504

  11. 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

  12. 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

  13. 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

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

    PubMed Central

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

    2015-01-01

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

  15. 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

  16. 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

  17. 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,

  18. 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

  19. Preretinal membranectomy in idiopathic preretinal macular fibrosis.

    PubMed

    Mandelcorn, M S; Liao, R

    1983-12-01

    Idiopathic preretinal macular fibrosis (PMF) rarely causes progressive loss of vision. In 5 of 350 cases in which vision did markedly diminish, pars plana vitrectomy and membranectomy proved to be a useful surgical method of correcting the visual loss. There was an apparent recurrence of PMF in two of the five cases. PMID:6671151

  20. Lamellar macular hole after intravitreal ocriplasmin injection.

    PubMed

    Chod, Ross Bronson; Goodrich, Clifford; Saxena, Sandeep; Akduman, Levent

    2015-01-01

    Intravitreal ocriplasmin was recently approved by the Food and Drug Administration to achieve medical vitreolysis in the setting of vitreomacular adhesion (VMA). We report a case of a 76-year-old woman who developed a lamellar macular hole following treatment with intravitreal ocriplasmin injection for VMA. A pathophysiological mechanism to explain this previously unreported complication of ocriplasmin injection is proposed. PMID:25576512

  1. 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…

  2. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema

    PubMed Central

    2015-01-01

    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, 6110 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, NCT01627249.) PMID:25692915

  3. Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring.

    PubMed

    Clemens, Christoph R; Eter, Nicole

    2016-01-01

    Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation. PMID:26489018

  4. 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

  5. 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

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

    PubMed

    Wang, Quan; Moerner, W E

    2015-11-10

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

  7. Fully Automatic Software for Retinal Thickness in Eyes With Diabetic Macular Edema From Images Acquired by Cirrus and Spectralis Systems

    PubMed Central

    Lee, Joo Yong; Chiu, Stephanie J.; Srinivasan, Pratul P.; Izatt, Joseph A.; Toth, Cynthia A.; Farsiu, Sina; Jaffe, Glenn J.

    2013-01-01

    Purpose. To determine whether a novel automatic segmentation program, the Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can be applied to spectral-domain optical coherence tomography (SD-OCT) images obtained from different commercially available SD-OCT in eyes with diabetic macular edema (DME). Methods. A novel segmentation framework was used to segment the retina, inner retinal pigment epithelium, and Bruch's membrane on images from eyes with DME acquired by one of two SD-OCT systems, Spectralis or Cirrus high definition (HD)-OCT. Thickness data obtained by the DOCTRAP software were compared with those produced by Spectralis and Cirrus. Measurement agreement and its dependence were assessed using intraclass correlation (ICC). Results. A total of 40 SD-OCT scans from 20 subjects for each machine were included in the analysis. Spectralis: the mean thickness in the 1-mm central area determined by DOCTRAP and Spectralis was 463.8 107.5 ?m and 467.0 108.1 ?m, respectively (ICC, 0.999). There was also a high level agreement in surrounding areas (out to 3 mm). Cirrus: the mean thickness in the 1-mm central area was 440.8 183.4 ?m and 442.7 182.4 ?m by DOCTRAP and Cirrus, respectively (ICC, 0.999). The thickness agreement in surrounding areas (out to 3 mm) was more variable due to Cirrus segmentation errors in one subject (ICC, 0.7340.999). After manual correction of the errors, there was a high level of thickness agreement in surrounding areas (ICC, 0.9971.000). Conclusions. The DOCTRAP may be useful to compare retinal thicknesses in eyes with DME across OCT platforms. PMID:24084089

  8. 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-?B 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-?B 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

  9. Visual outcome of ranibizumab therapy for neovascular age related macular degeneration in the black population: a report of five cases

    PubMed Central

    Vemala, Roopa; Gupta, Bhaskar; Sivaprasad, Sobha

    2010-01-01

    Introduction: Neovascular age related macular degeneration (AMD) is relatively uncommon in the black population. We report the 12-month outcome of ranibizumab therapy in five black patients with choroidal neovascular membrane (CNV) secondary to AMD. Material and methods: Retrospective analysis of a prospective audit database maintained for all patients on ranibizumab therapy in a retinal specialist unit that caters to a multi-ethnic cohort in London, United Kingdom. Results: At 12 months, all the 5 patients maintained stable vision (loss of less than 15 ETDRS letters). However, none of them gained more than 15 ETDRS letters. All eyes showed early subretinal fibrosis while 2 patients showed extended areas of retinal pigment atrophy. Conclusion: Our case studies indicate that ranibizumab stabilizes the vision in black patients with CNV secondary to AMD but they tend to develop early subretinal fibrosis and retinal pigment atrophy. PMID:20823932

  10. 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

  11. [Pigmentation disorders in systemic sclerodermia].

    PubMed

    Gonin, M; Gerster, J C

    1994-01-11

    Skin pigmentation changes in systemic sclerosis have been known since the end of the last century. Many different aspects have been described. We report the case of a 48-year-old man with severe progressive systemic sclerosis who presented many different types of pigmentation changes of skin, but particularly a severe hyperpigmentation. This clinical observation suggests that local factors, including repetitive friction, trauma or variations in skin temperature, may influence the development, distribution and severity of pigmentation abnormalities in patients with systemic sclerosis. Physical treatments (connective tissue massage and lymphatic drainage) were very beneficial for our patient (healing of skin ulcerations and decrease of pigmentation. PMID:8296125

  12. Outcomes of 23-gauge pars plana vitrectomy and internal limiting membrane peeling with brilliant blue in macular hole

    PubMed Central

    Sanisoglu, Huseyin; Sevim, Mehmet Sahin; Aktas, Betul; Sevim, Semra; Nohutcu, Ahmet

    2011-01-01

    Purpose: The evaluation of anatomic and visual outcomes in macular hole cases treated with internal limiting membrane (ILM) peeling, brilliant blue (BB), and 23-gauge pars plana vitrectomy (PPV). Materials and methods: Fifty eyes of 48 patients who presented between July 2007 and December 2009 with the diagnosis of stage 2, 3, or 4 macular holes according to Gass Classification who had undergone PPV and ILM peeling were included in this study. Pre- and postoperative macular examinations were assessed with spectral-domain optical coherence tomography. 23 G sutureless PPV and ILM peeling with BB was performed on all patients. Results: The mean age of patients was 63.34 9.6 years. Stage 2 macular hole was determined in 17 eyes (34%), stage 3 in 24 eyes (48%), and stage 4 in 9 eyes (18%). The mean follow-up time was 13.6 1.09 months. Anatomic closure was detected in 46/50 eyes (92%), whereas, in four cases, macular hole persisted and a second operation was not required due to subretinal fluid drainage. At follow-up after 2 months, persistant macular hole was detected in one case and it was closed with reoperation. At 12 months, an increase in visual acuity in 41 eyes was observed, while it remained at the same level in six eyes. In three eyes visual acuity decreased. There was a postoperative statistically significant increase in visual acuity in stage 2 and 3 cases (P < 0.05), however, no increase in visual acuity in stage 4 cases was observed. Conclusion: PPV and ILM peeling in stage 2, 3, and 4 macular hole cases provide successful anatomic outcomes, however, in delayed cases, due to photoreceptor loss, it has no effect on functional recovery. BB, used for clarity of ILM, may be beneficial due to its low retinal toxicity. PMID:21887101

  13. Alcohol- and light-induced electro-oculographic responses in age-related macular degeneration & central serous chorioretinopathy. alcohol- and light-induced EOG responses in ARMD & CSC.

    PubMed

    Wu, Kathy H C; Marmor, Michael F

    2005-01-01

    The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7 eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11 patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 normal controls. We recorded the alcohol-induced EOG response after a single oral administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood alcohol levels were monitored with a breath analyzer. We found that neither the alcohol-EOG nor the light-induced EOG response showed any difference between either ARMD or CSC patients and normal controls. Nor was there difference among eyes of different ARMD or CSC subgroups. In addition, blood alcohol concentrations near the time of the alcohol-EOG peak showed no obvious relationship with peak/baseline ratios. These data suggest that neither the alcohol- nor the light-induced EOG is a sensitive indicator of these diseases. PMID:16328932

  14. 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

  15. 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.

  16. 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

  17. Increased cone sensitivity to ABCA4 deficiency provides insight into macular vision loss in Stargardt's dystrophy.

    TOXLINE Toxicology Bibliographic Information

    Conley SM; Cai X; Makkia R; Wu Y; Sparrow JR; Naash MI

    2012-07-01

    Autosomal recessive Stargardt macular dystrophy is caused by mutations in the photoreceptor disc rim protein ABCA4/ABCR. Key clinical features of Stargardt disease include relatively mild rod defects such as delayed dark adaptation, coupled with severe cone defects reflected in macular atrophy and central vision loss. In spite of this clinical divergence, there has been no biochemical study of the effects of ABCA4 deficiency on cones vs. rods. Here we utilize the cone-dominant Abca4(-/-)/Nrl(-/-) double knockout mouse to study this issue. We show that as early as post-natal day (P) 30, Abca4(-/-)/Nrl(-/-) retinas have significantly fewer rosettes than Abca4(+/+)/Nrl(-/-) retinas, a phenotype often associated with accelerated degeneration. Abca4-deficient mice in both the wild-type and cone-dominant background accumulate more of the toxic bisretinoid A2E than their ABCA4-competent counterparts, but Abca4(-/-)/Nrl(-/-) eyes generate significantly more A2E per mole of 11-cis-retinal (11-cisRAL) than Abca4(-/-) eyes. At P120, Abca4(-/-)/Nrl(-/-) produced 340 121 pmoles A2E/nmol 11-cisRAL while Abca4(-/-) produced 50.4 8.05 pmoles A2E/nmol 11-cisRAL. Nevertheless, the retinal pigment epithelium (RPE) of Abca4(-/-)/Nrl(-/-) eyes exhibits fewer lipofuscin granules than the RPE of Abca4(-/-) eyes; at P120: Abca4(-/-)/Nrl(-/-) exhibit 0.045 0.013 lipofuscingranules/?m of RPE vs. Abca4(-/-) 0.17 0.030 lipofuscingranules/?m of RPE. These data indicate that ABCA4-deficient cones simultaneously generate more A2E than rods and are less able to effectively clear it, and suggest that primary cone toxicity may contribute to Stargardt's-associated macular vision loss in addition to cone death secondary to RPE atrophy.

  18. Macular atrophy after combined intravitreal triamcinolone and photodynamic therapy to treat choroidal neovascularization

    PubMed Central

    Ruiz-Moreno, Jos M; Montero, Javier A; Amat, Pedro; Lugo, Francisco

    2010-01-01

    AIM To report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD). METHODS The present study was retrospective about non-randomized interventional case series. Fifty-one consecutive eyes with subfoveal (all types) CNV associated with AMD were treated by PDT and intravitreal (19.42.1)mg per 0.1mL TA at the Alicante Institute of Ophthalmology. The appearance of macular choriocapillaris and retinal pigment epithelium (RPE) atrophy was considered at two years follow-up. Thirty consecutive eyes treated by PDT alone, matched for age, sex, and type and size of CNV were considered as control group. RESULTS Twenty-one of 47 eyes in the study group (45%) and 7 of 30 eyes in the control group (23%) developed macular RPE and choriocapillaris atrophy in the treated area at month 24 (P=0.04, Chi-square test). The greatest diameter of the atrophic areas averaged (50441666)m in the study group vs (43451550)m in the control group. Mean final best corrected visual acuity (logarithm of minimal angle of resolution) was (0.870.33) in the cases with RPE atrophy vs (0.660.26) in the cases with no RPE atrophy in the study group (P=0.11, Mann-Whitney U test). CONCLUSION The association of high doses of intravitreal TA and PDT may increase the risk for RPE and choriocapillaris atrophy. PMID:22553543

  19. 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

  20. 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

  1. Fundus autofluorescence imaging in age-related macular degeneration and geographic atrophy.

    PubMed

    Bearelly, Srilaxmi; Cousins, Scott W

    2010-01-01

    The traditional method for documenting and quantifying geographic atrophy (GA) is color photography. This method has been shown to be reproducible in several clinical trials, including the Age-related Eye Disease Study (AREDS) and the natural progression of GA studies by Sunness et al. (AREDS No. 6, Am J Ophthalmol 132(5):668-681, 2001; Sunness et al., Invest Ophthalmol Vis Sci 40(8):1761-1769, 1999). Nevertheless, it can be difficult to distinguish between dead/nonfunctioning retinal pigment epithelium (RPE), living but depigmented RPE (RPE often release melanin granules upon injury), and yellowish coloration caused by large drusen or calcified regressed drusen. Two imaging technologies that seem promising are fundus autofluorescence (FAF) and spectral domain (high resolution) optical coherence tomography (SDOCT). Here we provide an overview of FAF imaging in the setting of age-related macular degeneration (AMD) and GA. PMID:20238040

  2. 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

  3. Early features in acute macular neuroretinopathy.

    PubMed

    Garg, Anurag; Shah, Anish N; Richardson, Theresa; O'Sullivan, Eoin; Eleftheriadis, Haralabos

    2014-06-01

    Acute macular neuroretinopathy (AMNR) is a rare disorder characterised by acute onset of unilateral or bilateral visual impairment associated with reddish-brown wedge-shaped outer macular lesions. It is more frequently reported in young females and though the pathophysiology remains unclear, factors reported in association with its onset include post-viral illness and vasoconstrictor use. We report a case of AMNR in an 18-year old female patient presenting with a 2-day history of acute painless blurring of central vision bilaterally, following 1 month of preceding flu-like illness. For 1 week prior to presentation, the patient had taken large doses of oral preparations containing phenylephrine hydrochloride. In addition to demonstrating characteristic optical coherence tomography findings seen in AMNR, we illustrate some rarely seen acute ophthalmoscopic features. Based on associations from this case, we add further insight into the pathophysiology of this condition which remains poorly understood. PMID:24037593

  4. Macular degeneration: a possible biochemical mechanism.

    PubMed

    Soloway, Albert H; Curley, Robert W; Soloway, Scott M

    2011-05-01

    The possible role of labile endogenous metabolites in the cause of various chronic debilitating diseases such as macular degeneration has not been adequately explored. In the metabolism of the various retinoids, namely retinal (vitamin A aldehyde), retinol (vitamin A alcohol) and retinoic acid, each has the potential for generating labile intermediates, such as their corresponding 5,6-epoxides by the action of various cytochrome P(450)s. Such retinoid epoxides may well have the capacity for acting as toxins upon the neurons in the macula unless they are rapidly hydrolyzed by epoxide hydrolases. Since the cytochrome P(450)s responsible for epoxide formation and the various epoxide hydrolases involved in their hydrolysis are determined genetically, this may serve to explain a genetic component being involved in the causation of age-related macular degeneration. PMID:21349651

  5. 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

  6. 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

  7. 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

  8. PERIFOVEAL VITREOUS DETACHMENT AND ITS MACULAR COMPLICATIONS

    PubMed Central

    Johnson, Mark W

    2005-01-01

    Purpose To evaluate the vitreoretinal relationship in eyes with idiopathic macular disorders putatively caused by vitreomacular traction associated with early stages of age-related posterior vitreous detachment (PVD). Methods Retrospective observational case series of 43 eyes of 40 patients diagnosed with one of several idiopathic vitreomacular conditions. Included patients had no biomicroscopic evidence for complete PVD on presentation and underwent a specific clinical assessment of the vitreoretinal relationship. Affected eyes were evaluated with slit-lamp biomicroscopy, B-scan ultrasonography, optical coherence tomography, and/or intraoperative examination of the posterior hyaloid. Results By one or more examination techniques, 41 (95.3%) of the 43 study eyes had evidence of vitreous detachment from the perifoveal macular region and the remaining two eyes had complete PVD. When measurable, the size of the vitreomacular adhesion varied by diagnosis. Of 31 eyes with perifoveal vitreous detachment seen in follow-up, only three (9.7%) showed progression to complete PVD over an average preoperative or total follow-up period of 30.0 months (range, 2 to 237 months). Surgical or spontaneous separation of the residual vitreomacular adhesion in 16 eyes was followed in 15 (93.8%) by partial or complete resolution of the symptoms and signs of macular traction. Conclusions Age-related PVD appears to be an insidious, chronic event that begins in the perifoveal macula and evolves over a prolonged period of time prior to vitreopapillary separation. Though usually asymptomatic, its early (perifoveal) stages may be complicated by one of several macular pathologies, determined in part by the size of the residual vitreomacular adhesion. PMID:17057817

  9. Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age-related macular degeneration

    PubMed Central

    Kaneko, Hiroki; Ye, Fuxiang; Ijima, Ryo; Kachi, Shu; Kato, Seiichi; Nagaya, Masatoshi; Higuchi, Akiko; Terasaki, Hiroko

    2014-01-01

    BACKGROUND AND PURPOSE The present treatment for choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) is not sufficient. Hence, we examined the therapeutic efficacy of reducing histamine H4 receptor expression on CNV in mice. EXPERIMENTAL APPROACH H4 receptor expression was examined in CNVs from patients with AMD. In mice, laser photocoagulation was performed in the retina to induce experimental CNV (laser CNV). Protein and mRNA expression levels were determined and CNV volume measured in wild-type and Hrh4-/- mice with laser CNV. The effects of JNJ7777120, an H4 receptor antagonist, administered intravitreously, on CNV volume and pathological vessel leakage were determined in mice with laser CNV and controls. Fundus imaging, retinal histology and electroretinography were performed on eyes injected with JNJ7777120 to evaluate retinal toxicity. KEY RESULTS Human H4 receptors were only confirmed in CNV samples from AMD patients and not in the other subretinal tissues. Mouse H4 receptors were expressed in retinal pigment epithelium only after inducing laser CNV in wild-type mice, and were co-localized with the macrophage marker F4/80. Laser CNV volume was reduced in Hrh4-/- mice compared with that in wild-type mice, and JNJ7777120 suppressed laser-induced CNV volume and pathological CNV leakage in wild-type mice. Also eyes injected with JNJ7777120 did not show retinal degeneration. CONCLUSIONS AND IMPLICATIONS H4 receptors are expressed in macrophages that accumulate around CNVs. Suppressing H4 receptor expression prevented the pathological vessel leakage without showing retinal toxicity, indicating that the H4 receptor has potential as a novel therapeutic target in AMD. PMID:24787705

  10. 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

  11. 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

  12. [Differential diagnosis of pigmented tumors].

    PubMed

    Hundeiker, M

    1979-05-10

    Some frequent diagnostic problems and the most important clinical and histologic criteria in differential diagnosis of malignant melanomas, benign pigment cell nevi, melanotic epithelial neoplastic lesions and frequent haemosiderotic tumors are delineated in a condensed survey. Considering the variety of diagnostic errors, one should never treat respectively destroy pigmented tumors of the skin without histologic investigation. PMID:218872

  13. 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

  14. 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.

  15. 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.

  16. 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

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

    PubMed Central

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

    2011-01-01

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

  18. 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.

  19. 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

  20. 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

  1. 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-Sttz, 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

  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. Iris pigmentation and photopic visual acuity: a preliminary study.

    PubMed

    Short, G B

    1975-11-01

    Visual acuity under varying conditions of light stress was tested in four human populations. It was found that the density of iris pigmentation had no significant effect on visual acuity under conditions of bright light. While some acclimatization to local light levels was observed, significant population differences in visual acuity were obtained. A hypothesis is advanced at to the adaptive value of varying densities of pigmentation of the iris based on the known heat absorption properties of melanin granules. PMID:1211437

  4. [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

  5. Mapping of Photosynthetic Pigments in Spanish Reservoirs

    NASA Astrophysics Data System (ADS)

    Pea-Martinez, R.; Domnguez-Gmez, J.-A.; de Hoyos, C.; Ruiz-Verd, A.

    2004-05-01

    We present the preliminary results of the first stage of the project AO-594, which comprises the development and calibration of algorithms for photosynthetic pigment mapping in Spanish reservoirs. In the years 2001-2002, an extensive field campaign was made in 36 reservoirs and lakes in order to obtain a database of Rrs spectra (400-1000 nm), photosynthetic pigments concentration and phytoplankton composition. The sampled water bodies cover a wide range of environmental conditions, trophic levels and phytoplankton communities. As a first approach in algorithm development, we have explored the relationships between ratios of MERIS bands and pigment concentrations through simple linear regression analysis. The bands have been selected based on the spectral properties of each pigment and a peak analysis of the Rrs spectra. For chlorophyll a, we have found a very good linear relationship (R2 =0.919) using the ratio between bands 9 and 7. Similar results are found using band 8 instead of 7. In any case, the model derived for the whole range of concentrations (0-500 mg m3 ) fails for low values (<15 mg m-3 ). Possible solutions include the use of - non-linear models or the use of two different models depending on the ratio values. For cyanobacteria detection, the ratio between bands 9 and 6 (the later centred at 620 nm) shows a good correlation (R2 =0.723) with phycocyanin concentration measured fluorometrically, and better (R2 =0.945) with zeaxanthin measured using HPLC. The correlation of other indicator pigments with MERIS band ratios is less strong, but is still possible to develop algorithms accurate enough for bloom monitoring. We also discuss the problems found with the L2 MERIS reflectance imagery that we have tried to use for model calibration. We present the results of the study carried on six reservoirs in northeastern Spain. In a date coincident with a MERIS image (June 19th, 2003) we have collected pigment concentration and reflectance data measured from a boat and 10 m resolution imagery for the 15 MERIS bands acquired with an airborne CASI-2 sensor. This three-level data has allowed us to calculate a new set of reflectance MERIS bands from the L1B imagery and compare them with the L2 imagery. The comparison could be useful for modifying the current atmospheric correction algorithms applied for L2 data generation, which we have observed that frequently fail in inland waters.

  6. 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

  7. 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

  8. 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

  9. 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

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

    PubMed

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

    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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Episcleral macular buckling for posterior retinal detachment in silicone oil filled eyes associated with myopic macular hole

    PubMed Central

    Tian, Jiao; Tang, Luo-Sheng; Guo, Xiao-Jian; Luo, Yong-Heng

    2013-01-01

    AIM To evaluate anatomical and visual outcomes of episcleral macular buckling (EMB) for posterior retinal detachment in silicone oil filled eyes associated with myopic macular hole. METHODS Five cases of EMB for initial failure of retinal reattachment after internal limiting membrane (ILM) peeling and silicone oil tamponade caused by myopic macular hole were retrospectively reviewed. A silicone sponge sutured directly across the macular region was performed on the silicone oil filled eyes. Silicone oil was removed no sooner than 1 month post-EMB. The duration of follow-up time after removalof silicone oil was more than 3 months. RESULTS Retinas of five eyes were all reattached at the last follow-up. The postoperative vision ranged from counting fingers to 0.08. CONCLUSION Anatomical results improved after EBM for posterior retinal detachment in silicone oil filled eyes associated with myopic macular hole, which was not evident for visual outcome. PMID:23638417

  17. Outcomes of chronic macular hole surgical repair

    PubMed Central

    Shukla, Shripaad Y; Afshar, Armin R; Kiernan, Daniel F; Hariprasad, Seenu M

    2014-01-01

    Purpose: To report visual and anatomic outcomes of chronic macular hole surgery, with analysis of pre-operative OCT-based hole size and post-operative closure type. Settings and Design: An IRB-approved, retrospective case series of 26 eyes of 24 patients who underwent surgery for stage 3 or 4 idiopathic chronic macular holes at a tertiary care referral center. Statistical Analysis: Student's t-test. Results: Nineteen of 26 eyes (73%) had visual improvement after surgery on most recent exam. Twenty-one of 26 eyes (81%) achieved anatomic closure; 16 of 26 eyes (62%) achieved type 1, and five of 26 eyes (19%) achieved type 2 closure. Post-operative LogMAR VA for type 1 closure holes (0.49) was significantly greater than for type 2 closure and open holes (1.26, P < 0.003 and 1.10, P < 0.005, respectively), despite similar pre-operative VA (P = 0.51 and 0.68, respectively). Mean pre-operative hole diameter for eyes with type 1 closure, type 2 closure, and holes that remained open were 554, 929, and 1205 microns, respectively. Mean pre-operative hole diameter was significantly larger in eyes that remained open as compared to eyes with type 1 closure (P = 0.015). Conclusion: Vitrectomy to repair chronic macular holes can improve vision and achieve long-term closure. Holes of greater than 3.4 years duration were associated with a greater incidence of remaining open and type 2 closure. Larger holes (mean diameter of 1205 microns) were more likely to remain open after repair. PMID:25116773

  18. Novel compstatin family peptides inhibit complement activation by drusen-like deposits in human retinal pigmented epithelial cell cultures.

    PubMed

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

    2013-11-01

    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

  19. Treatment of age-related macular degeneration.

    PubMed

    Bylsma, Guy W; Guymer, Robyn H

    2005-09-01

    Age-related macular degeneration (AMD) is the greatest cause of legal blindness in the western world. Established treatments include argon laser photocoagulation of extrafoveal choroidal neovascularisation (CNV) and photodynamic therapy of selected sub-foveal CNV. Newer approaches are targeting the angiogenic pathway in CNV development. Currently, other treatment modalities, such as radiotherapy and transpupillary thermotherapy do not have a clear role to play. Surgical options are experimental and only available in some centres for selected patients. Prevention of AMD remains elusive. Dietary supplements may have a role, while statins and prophylactic laser photocoagulation of drusen remain experimental. This paper explains the principles behind these approaches. PMID:16255691

  20. 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

  1. [Pharmacological treatment for diabetic macular edema].

    PubMed

    Fukumoto, Masanori; Ikeda, Tsunehiko

    2015-03-01

    Diabetic macular edema(DME) is a major cause of vision loss and has a remarkable impact on the quality of life of diabetic patients. New pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have recently been developed for the treatment of DME. Even though laser therapy has been the standard treatment for DME, the results of several clinical trials have shown the superiority of some of these new agents to laser therapy. The purpose of this review is to briefly summarize the currently available new pharmacological treatments for DME in Japan. PMID:25812378

  2. Surgery for pre-macular fibrosis.

    PubMed

    Muralidhar, N S; Playfair, T J; Gregory-Roberts, J C

    1990-02-01

    We review 12 consecutive cases of pre-macular fibrosis (PMF) treated by vitreous surgical techniques. The causes of PMF included retinal detachment surgery in four patients, idiopathic in three patients, laser treatment in three patients, pars planitis in one patient and diabetic retinopathy in one patient. The membrane was successfully removed in all the patients. One patient developed a retinal detachment that was repaired successfully. All patients had improved visual acuity (VA) of two Snellen lines or more and six patients achieved VA of 6/12 or better. Patients with PMF following retinal detachment had poorer final VA. PMID:2357363

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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, 6110 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.).

  8. 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

  9. Clinical features of idiopathic preretinal macular fibrosis. Schoenberg Lecture.

    PubMed

    Wise, G N

    1975-03-01

    Of 150 consecutive cases of preretinal macular fibrosis that occurred predominantly in older subjects, 118 cases involved only one eye while 32 occurred binocularly. The ratio of women to men was 3:2. Visual acuity was usually 20/50 or better, and only four of 178 eyes had acuity below 20/200. The vast majority of lesions involved the macula and few extended outside the macular zone. The characteristic clinical finding on ophthalmoscopy was a glinting reflex probably due to a layer of connective tissue cells lying on the internal limiting membrane. Small white exudates, venous abnormalities, and occasional hemorrhages may also be part of prepretinal macular fibrosis. Amsler grid testing usually demonstrated irregularity and distortion of some part of the grid. Fluorescein angiography revealed a characteristic tortuosity of the small macular vessels. Most eyes had previous posterior vitreous detachments but, except for one possible case, there were no cases where the posterior vitreous body was adherent to either the retinal membrane or the macular region. There was no significant systemic disease related to preretinal macular fibrosis. In most instances, preretinal macular fibrosis either was stationary or slowly progressive. The etiology and treatment of the condition remains obscure. PMID:1121990

  10. 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

  11. 'Idiopathic' preretinal macular fibrosis in young individuals.

    PubMed

    Laatikainen, L; Punnonen, E

    1987-02-01

    In order to evaluate possible etiological factors and the natural course of 'idiopathic' preretinal fibrosis in young persons, nine consecutive patients with macular pucker diagnosed under the age of 50 years were examined. There were six women and three men with the mean age of 27.2 years (range 15-50) and the mean follow-up of 4.5 years (range 1.5-10). The initial visual acuity varied from 0.25 to 1.0. The preretinal membrane was either central or paramacular. In two eyes the process was probably congenital (retinal hamartoma), one was postinflammatory (retinal vasculitis), and one was associated with sclerosis of the anomalous macular arterioles. In the others no causative factors were discovered. In seven of the nine eyes both the visual acuity and the fibrotic process remained stable, in one eye the vision improved, and in one eye deteriorated. It seems that most young persons with 'idiopathic' preretinal fibrosis of the macula can be followed up without surgical removal of the membrane. PMID:3557800

  12. Prognostic factors in idiopathic preretinal macular fibrosis.

    PubMed

    Akiba, J; Yoshida, A; Trempe, C L

    1991-01-01

    We retrospectively studied 124 eyes with idiopathic preretinal macular fibrosis to assess the value of fluorescein angiography and vitreous examination for predicting the visual prognosis. During a mean follow-up period of 43 months (range, 12-14 months), the visual acuity of 33 eyes (27%) declined two or more lines from the initial value, although the appearance of the fibrosis remained unchanged in 114 cases (92%). At initial examination, 38 eyes (31%) showed fluorescein leakage into the macula; these eyes were more prone to further visual deterioration than were those without leakage (P less than 0.05). Of 14 eyes with partial vitreous detachment and vitreous traction to the fibrosis, 6 (43%) had a final visual acuity of 20/200 or worse; this proportion was significantly higher than that found either in eyes with no detachment or in those with complete vitreous detachment (P less than 0.05). The presence of fluorescein leakage and/or vitreous traction to the fibrosis may predict worse functional prognosis in eyes with idiopathic preretinal macular fibrosis. PMID:2044966

  13. 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

  14. 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

  15. 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, Brengre; 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

  16. 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

  17. Role of the vitreous in idiopathic preretinal macular fibrosis.

    PubMed

    Hirokawa, H; Jalkh, A E; Takahashi, M; Takahashi, M; Trempe, C L; Schepens, C L

    1986-02-15

    Of 250 eyes with idiopathic preretinal macular fibrosis, 56 had no posterior vitreous detachment (Group 1), ten had partial posterior vitreous detachments without vitreous traction to the macula (Group 2), 29 had partial posterior vitreous detachments with vitreous traction to the macula (Group 3), and 155 had complete posterior vitreous detachments (Group 4). There were significantly more eyes with visual acuities of 20/60 or worse, cystoid macular changes, or macular fluorescein leakage in Group 3 than in Group 1 or Group 4. Thus, the presence of vitreous traction to the macula was associated with worse anatomic and functional findings. PMID:3946531

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

    PubMed Central

    2014-01-01

    Background The association of inflammatory factors and the aqueous flare value with macular edema in branch retinal vein occlusion (BRVO) patients remains unclear. The relationship between the aqueous flare value and the vitreous fluid levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble VEGF receptor-2 (sVEGFR-2) was evaluated to investigate the role of inflammation in BRVO associated with macular edema. Aqueous flare values and the vitreous levels of VEGF, IL-6, MCP-1, sICAM-1, and sVEGFR-2 were compared between previously untreated patients with BRVO and patients with macular hole (MH). Methods Vitreous samples were obtained from 45 patients during vitreoretinal surgery (28 patients with BRVO and 17 with MH), and the levels of VEGF, IL-6, MCP-1, sICAM-1, and sVEGFR-2 were measured by enzyme-linked immunosorbent assay. Retinal ischemia was evaluated by measuring the area of capillary non-perfusion using fluorescein angiography and the Scion Image program. Aqueous flare values were measured with a laser flare meter and macular edema was examined by optical coherence tomography. Results The median aqueous flare value was significantly higher in the BRVO group (12.1 photon counts/ms) than in the MH group (4.5 photon counts/ms, P?levels of VEGF, IL-6, MCP-1, and sICAM-1 in the BRVO group (??=?0.54, P?=?0.005; ??=?0.56, P?=?0.004; ??=?0.52, P?=?0.006; and ??=?0.47, P?=?0.015, respectively). The aqueous flare value was also significantly correlated with the foveal thickness in the BRVO group (??=?0.40, P?=?0.037). Conclusions Inflammation may induce an increase of vascular permeability and disrupt the blood-aqueous barrier via release of inflammatory factors (VEGF, IL-6, MCP-1, and sICAM-1) in BRVO patients with macular edema. PMID:24884703

  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. 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??m to 286??m) 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??m to 279??m). 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??m to 279??m). Conclusion. Treatment of macular oedema secondary to MacTel with Ozurdex demonstrated promising anatomical outcomes. However, visual outcomes continued to gradually deteriorate. PMID:25045562

  1. Evaluation of circulating miRNAs in wet age-related macular degeneration

    PubMed Central

    Y?ld?r?m, zlem; Din, Erdem; Ayaz, Lokman; Fidanc?, ?enay Balc?; Tamer, Llfer

    2014-01-01

    Purpose In the present study, we aimed to investigate the changes in plasma miRNA in patients with wet age-related macular degeneration. Methods The expression profiles of 384 miRNAs in plasma from 33 patients (22 male, 11 female) who were diagnosed with wet age-related macular degeneration with fundus examination, fundus fluorescein angiography, and optical coherence tomography and 31 controls (17 male, 14 female) were evaluated using high-throughput quantitative real-time PCR. Results Our results demonstrated that the expression level of five miRNAs (miR-17-5p, miR-20a-5p, miR-24-3p, miR-106a-5p, and miR-223-3p) was significantly upregulated in patients with age-related macular degeneration when compared to the control group (p<0.05). The expression level of 11 miRNAs (miR-21-5p, miR-25-3p, miR-140-3p, miR-146b-5p, miR-192-5p, miR-335-5p, miR-342-3p, miR-374a-5p, miR-410, miR-574-3p, and miR-660-5p) was significantly downregulated in patients (p<0.05). In addition, ten miRNAs (miR-26b-5p, miR-27b-3p, miR-29a-3p, miR-139-3p, miR-2123p, miR-324-3p, miR-324-5p, miR-532-3p, miR-744-5p, and miR-Let-7c) were expressed only in the patient group. Conclusions Our results suggest that plasma miRNA levels may change in wet age-related macular degeneration. These molecules may have an important therapeutic target in patients who are unresponsive to antivascular endothelial growth factor therapy. However, further studies must be conducted for possible effects of miRNAs in vascular disorders of eye such as age-related macular degeneration. PMID:25221421

  2. 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

  3. Chronic cystoid macular oedema treated with intravitreal dobesilate

    PubMed Central

    Cuevas, Pedro; Outeirio, Luis A; Angulo, Javier; Gimnez-Gallego, Guillermo

    2012-01-01

    Dobesilate is an anti-inflammatory and antipermeability agent. Intravitreal administration of this compound is a therapeutically beneficial agent in the treatment of chronic cystoid macular oedema. PMID:22778475

  4. Chronic cystoid macular oedema treated with intravitreal dobesilate.

    PubMed

    Cuevas, Pedro; Outeirio, Luis A; Angulo, Javier; Gimnez-Gallego, Guillermo

    2012-01-01

    Dobesilate is an anti-inflammatory and antipermeability agent. Intravitreal administration of this compound is a therapeutically beneficial agent in the treatment of chronic cystoid macular oedema. PMID:22778475

  5. Genetics Home Reference: Age-related macular degeneration

    MedlinePLUS

    ... form. The dry form is much more common, accounting for 85 to 90 percent of all cases ... Where can I find information about diagnosis or management of age-related macular degeneration? These resources address ...

  6. 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

  7. 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; Schnberg, Svanhild; Bjrky, 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

  8. 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

  9. Treatment of cystic macular lesions in hereditary retinal dystrophies.

    PubMed

    Salvatore, Serena; Fishman, Gerald A; Genead, Mohamed A

    2013-01-01

    Cystic macular lesions frequently contribute to impaired visual acuity in hereditary retinal dystrophies. Their pathogenesis varies and is not entirely understood. Carbonic anhydrase inhibitors have proven to be potentially efficacious, although not in all cases. We discuss the various factors and mechanisms implicated in the etiology of cystic macular lesions (anatomical abnormalities, impairment of the blood-retinal barrier, tangential vitreous traction, and mutations in retinoschin, etc.) and the various treatments that have been proposed. PMID:24160730

  10. Adenocarcinoma of retinal pigment epithelium.

    PubMed Central

    Ramahefasolo, S; Soubrane, G; Dhermy, P; Godel, V; Regenbogen, L; Coscas, G

    1987-01-01

    This report describes a 41-year-old man with an intraocular tumour misinterpreted clinically as choroidal melanoma. The fluorescein angiographic features were not fully characteristic of uveal malignancy, and indeed histopathology revealed the diagnosis of adenocarcinoma of the retinal pigment epithelium. It is suggested that, in cases with the fundus and angiographic findings described here, the rare possibility of adenocarcinoma of retinal pigment epithelium should be kept in mind. Of particular interest were the changing pathological findings in the various parts of the tumour, which paralleled the fluorescein angiographic pattern. Images PMID:3651364

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Perceptual learning in patients with macular degeneration.

    PubMed

    Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rhle, Sabine; Greenlee, Mark W

    2014-01-01

    Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex. PMID:25368597

  17. Perceptual learning in patients with macular degeneration

    PubMed Central

    Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rhle, Sabine; Greenlee, Mark W.

    2014-01-01

    Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex. PMID:25368597

  18. Diabetic Macular Edema: Options for Adjunct Therapy.

    PubMed

    Calvo, Pilar; Abadia, Beatriz; Ferreras, Antonio; Ruiz-Moreno, Oscar; Verdes, Guayente; Pablo, Luis E

    2015-09-01

    Diabetes mellitus (DM) is a chronic disease that affects 387 million people worldwide. Diabetic retinopathy (DR), a common complication of DM, is the main cause of blindness in the active population. Diabetic macular edema (DME) may occur at any stage of DR, and is characterized by vascular hyperpermeability accompanied by hard exudates within the macula. Medical and surgical therapies have dramatically reduced the progression of DR, and timely intervention can reduce the risk of severe vision loss by more than 90 %. In 2012, intravitreal ranibizumab became the first antivascular endothelial growth factor (anti-VEGF) agent approved for DME and, since then, many reports of the use of ranibizumab for DME have been promising. Randomized, prospective, multicenter clinical trials-most notably, RESOLVE, READ-2, RISE/RIDE, RESTORE, DRCR.net protocol I, and RETAIN-reported improvements in best-corrected visual acuity and decreased central retinal thickness as measured with optical coherence tomography in patients with DME. Similar treatment benefits have also been noted in clinical trials evaluating intravitreal aflibercept and bevacizumab (DAVINCI, VISTA/VIVID, and BOLT) and more recently DRCR.net protocol T. Intravitreal steroids (dexamethasone intravitreal implant and fluocinolone acetonide), particularly in refractory cases, also play a significant role in the management of DME (MEAD/CHAMPLAIN and FAMOUS/FAME studies). In summary, over the last 5 years, blocking VEGF and inflammation has been shown to improve visual outcomes in patients with macular edema due to DM, revolutionizing the treatment of center-involved DME and establishing a new standard of care. PMID:26242766

  19. Protocol optimization for enhanced production of pigments in Spirulina.

    PubMed

    Kumar, Devendra; Kumar, Neeraj; Pabbi, Sunil; Walia, Suresh; Dhar, Dolly Wattal

    2013-01-01

    Spirulina has attracted special attention due to its importance as human foodstuff and natural colours with specific functional properties. These functional properties have been attributed to phycobilins, carotenoids, phenolics and unsaturated fatty acids. Present study was conducted under controlled phytotron conditions to identify the efficient strains of Spirulina in terms of pigment synthesis and to optimize their enhanced production. Methodology for enhanced production was standardized by varying specific environmental parameters (light intensity, temperature, carbon dioxide concentration, pH and NaCl level). Different strains of Spirulina depicted variability and environmental parameters showed distinct influence on pigments. Growth and pigment production was recorded to be most efficient under optimized conditions of light intensity (70?molm(-2)s(-1)), temperature (30C), CO2 concentration (550 ppm and 750ppm), pH (10.5) and NaCl level (2gL(-1)). PMID:24764599

  20. Phytoplankton pigment chemotaxonomy of the northeastern Atlantic

    NASA Astrophysics Data System (ADS)

    Gibb, Stuart W.; Cummings, Denise G.; Irigoien, Xabier; Barlow, Ray G.; Fauzi, R.; Mantoura, C.

    Phytoplankton pigment distributions were studied between 62 and 37N in the northeastern Atlantic as a component of the NERC PRIME programme. At the northern end of the transect, waters were characterised by a surface chlorophyll a (CHL a) maximum of 500- 700 ng l -1 (0- 40 m). At the southern end, surface waters were virtually devoid of nutrients ( NO3-<0.5 ?M, NH4+<50 nM), and surface CHL a concentrations were <50 ng l -1. At 37N a well-defined deep CHL a maximum (DCM) was recorded between 60 and 100 m (350 ng l -1) . Highest concentrations of CHL a(1500 ?g l -1) were measured in the surface mixed layer to the south of a well-defined salinity and temperature front at 52.5N. Overall, 19'-hexanoyloxyfucoxanthin (HEX, up to 1120 ng l -1) was the dominant accessory pigment, although zeaxanthin (ZEA) was the major accessory pigment at 37N. Conversion of pigment data into quantitative estimates of algal class abundances indicated the composition of phytoplankton population was relatively stable in surface waters between 62 and 52.5N: Prymnesiophytes were the most abundant class, contributing a mean of 38% of the total CHL a, while cryptophytes (20%), chlorophytes (14%) and diatoms (15%) contributed the bulk of the remaining CHL a. Together, these four classes accounted for 79-92% of the total CHL a in this section of the transect. Immediately south of the front (52-50N), prymnesiophytes contributed approximately half of the total CHL a, while south of 50N there was a shift to a population dominated by cyanobacteria and prochlorophytes, which together accounted for a mean of 53% of the measured total CHL a at 37N. At 37N the contribution of cyanobacteria to total CHL a declined significantly with depth, and the DCM was dominated by prochlorophytes, prymnesiophytes and cryptophytes. Below the DCM, chrysophytes were the most abundant class of phytoplankton, contributing 30% of the total CHL a, with prymnesiophytes, prochlorophytes and cryptophytes also making significant contributions. The contribution of prymnesiophytes to total CHL a was found to be relatively stable throughout the water column (23%, SD 3%). Although highest concentrations of divinyl chlorophyll a (dvCHL a) were recorded in the DCM, the contribution of dvCHL a to total CHL a (dvCHL a + CHL a) was only 21-26% here compared to up to 48% (mean=339.6%) in surface waters. The ratio of [dvCHL a]: prochlorophyte biomass increased from 10 ng ?g C -1 in the surface 40 m to 56.9 ng ?g C -1 between 50 and 100 m. This corresponded to a rise in cellular dvCHL a from 0.215 to 1.83 fg cell -1 and thus significant photo-adaptation with depth. Hence, a component of the DCM fluorescence and pigment signals is the result of increased cellular pigmentation rather than from increases in biomass alone. On the basis of inter-pigment ratios, we suggest that the DCM was dominated by an Atlantic strain of prochlorophytes, adapted to lower light levels, while the surface oligotrophic layer was composed of a mixed population of both Atlantic and a higher light adapted Mediterranean strain. Correlation studies indicated the potential of CHL a, fucoxanthin (FUC) and HEX to serve as respective proxy markers of POC and the biominerals silicate (SiO 2) and calcite (CaCO 3) in surface waters ( r=0.49-0.78, p<0.001) and in depth profiles at northern latitudes (59 N, r=0.74 -0.75, p<0.001). However, poor correlations were observed in depth profiles at the southern end of the transect.

  1. 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.

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

    PubMed Central

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

    2015-01-01

    Activation of the Wnt/?-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 ?-catenin response transcription (CRT) induced with Wnt3a by promoting ?-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-?(TNF-?), and nuclear factor-?B (NF-?B), 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 ?-catenin phosphorylation and degradation. Therefore, Wnt5a has significant therapeutic potential for the treatment of AMD. [BMB Reports 2015; 48(9): 525-530] PMID:26246285

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

    PubMed

    Silvn, 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 ?M 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 ?M 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

  4. Nitrite Modification of Extracellular Matrix Alters CD46 Expression and VEGF Release in Human Retinal Pigment Epithelium

    PubMed Central

    Fields, Mark A.; Cai, Hui; Bowrey, Hannah E.; Moreira, Ernesto F.; Beck Gooz, Monika; Kunchithapautham, Kannan; Gong, Jie; Vought, Emma; Del Priore, Lucian V.

    2015-01-01

    Purpose Loss of CD46 has recently been implicated in choroidal neovascularization in mice. Herein we investigated the effect of nitrite modification of the extracellular matrix (ECM) as an in vitro model of aging and its effect on CD46 expression and vascular endothelial growth factor (VEGF) release in cocultured human retinal pigment epithelium (RPE). Methods ARPE-19 cells were plated onto RPE-derived ECM conditions (untreated; nitrite modified; nitrite modified followed by washing with Triton X-100; or nitrite modified followed by washing with Triton X-100 and coated with extracellular matrix ligands). Cells were cultured for 7 days and CD46 expression was analyzed by immunohistochemistry and Western blot. Additionally, CD46 short interfering RNA (siRNA) was transfected into ARPE-19 cells, and VEGF levels were determined by ELISA. Finally, in the same ECM conditions, ARPE-19 cells were challenged with normal human serum and VEGF levels determined by ELISA. Results CD46 is expressed on the basolateral surface of ARPE-19 cells on RPE-derived ECM. Nitrite modification of ECM reduced the expression of CD46 on ARPE-19 cells by 0.5-fold (P = 0.003) and increased VEGF release in ARPE-19 cells by 1.7-fold (P < 0.001). CD46 knockdown also increased release of VEGF on the apical and basal sides of ARPE-19 cells in culture by 1.3- (P = 0.012) and 1.2-fold (P = 0.017), respectively. Conclusions Nitrite modification of the ECM decreased CD46 expression and increased the release of VEGF from ARPE-19 cells. Changes in CD46 expression may lead to changes in VEGF and play a pathologic role in the development of age-related macular degeneration. PMID:26161984

  5. [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

  6. 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

  7. What is a vertebrate pigment cell?

    PubMed

    Schartl, Manfred; Larue, Lionel; Goda, Makoto; Bosenberg, Marcus W; Hashimoto, Hisashi; Kelsh, Robert N

    2016-01-01

    On the basis of discussions emerging from a workshop and discussions at the 7th meeting of the European Society for Pigment Cell Research in Geneva in 2012, this manuscript outlines useful criteria for defining the bona fide pigment cells as a functional entity of the vertebrate body plan and differentiating them from 'pigmented' cells in general. It also proposes a nomenclature for various types of pigment cells of vertebrates. PMID:26247887

  8. Omega-3 Fatty Acids and Age-Related Macular Degeneration.

    PubMed

    Souied, Eric H; Aslam, Tariq; Garcia-Layana, Alfredo; Holz, Frank G; Leys, Anita; Silva, Rufino; Delcourt, Ccile

    2015-12-01

    Against a background of considerable epidemiological and other evidence implicating omega-3 fatty acids in the prevention of age-related macular degeneration (AMD), the negative results of the Age-Related Disease Study 2 (AREDS2) were unexpected. The possibility that the design, setting, intake or subjects of AREDS2 may not have permitted the prophylactic potential of omega-3 to be adequately demonstrated is considered. Epidemiological studies had indicated potential preventative effects of omega-3, and an earlier randomised prospective study (NAT2) showed that patients who achieved high red blood cell membrane EPA/DHA (eicosapentaenoic acid/docosahexaenoic acid) levels were significantly protected against AMD compared with those with permanently low EPA/DHA levels. Various methodological differences between these studies are considered. NAT2 included a true placebo group, whereas control subjects in AREDS2 received a nutritional formula already found to be effective in AREDS1, but no placebo for DHA/EPA supplementation. Differences in the handling of non-compliant subjects and the formulation of the test formulations are considered. Given these considerations, and other lines of evidence from laboratory and clinical studies, closing the chapter on omega-3 in AMD prevention may be premature. PMID:26610051

  9. 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

  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; Gtzinger, Erich; Pircher, Michael; Sattmann, Harald; Schtze, 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. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Pigment dispersants. 178.3725 Section 178.3725... 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in food-contact materials....

  12. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  13. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  14. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  15. 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

  16. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of...

  17. 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

  18. The mRNA expression of cytokines and their receptors in cultured iris pigment epithelial cells: a comparison with retinal pigment epithelial cells.

    PubMed

    Kociok, N; Heppekausen, H; Schraermeyer, U; Esser, P; Thumann, G; Grisanti, S; Heimann, K

    1998-08-01

    It has been suggested that human iris pigment epithelial (IPE) cells isolated from iridectomized tissue could be used as autologous cells for transplantation into the subretinal space in diseases with dysfunctional retinal pigment epithelium (RPE). RPE cells synthesize a number of cytokines and their receptors which are important for its proper function. Nearly nothing is known about the capacity of IPE to synthesize cytokines or responding to them. To compare the mRNA expression of 36 cytokines or their receptors in cultured adult IPE cells and RPE cells we used semi-quantitative reverse transcription polymerase chain reactions (RT-PCR). Included in our assay were cytokines with known expression in RPE to get a broad basis for comparing IPE cells: basic fibroblast growth factor (bFGF or FGF-2), and one of its receptor (FGFR-1), epidermal growth factor (EGF), and its receptor EGF-R, transforming growth factor beta(TGFbeta), and its type III receptor TGFbeta-R3, the platelet-derived growth factors and receptors (PDGF A, PDGF B, PDGF-Ralpha, PDGF-Rbeta), tumor necrosis factor alpha(TNFalpha), and two receptors TNF-R1 and TNF-R2, insulin (INS) with receptor INS-R, insulin-like growth factors (IGF1, IGF2), and receptors (IGF1-R, IGF2-R), vascular endothelial growth factor (VEGF), and two receptors (VEGF-R1 or FLT-1 and VEGF-R2 or FLK-1), the receptor for VEGF-C: VEGF-R3 or FLK-4, interleukin 6 (IL6), and its receptor (IL6-R), nerve growth factor (NGF), interleukin 1alpha(IL1alpha), and a receptor (IL1-R). In addition, cytokines or their receptors not known to be expressed in RPE were included to widen our picture of cytokine gene expression in the eye: stem cell factor (SCF), its receptor (SCF-R), low-affinity nerve growth factor receptor p75 (p75(NGF-R), ciliary neutrothropic factor (CNTF), and its receptor (CNTF-R), glycoprotein 130 interleukin 6 transducer (gp130 (IL6-SD), leukemia inhibitory factor (LIF), and its receptor (LIF-R). Semi-quantitative expression data were obtained using series of fivefold dilutions of each cDNA and a fixed number of PCR cycles. The expression of RPE 65, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and beta2-microglobulin (B2MG) was used as a control for cellular origin, RNA quality and PCR conditions. With the exception of insulin and tumor necrosis factor alphaall other cytokines analysed and their receptors were expressed in both IPE and RPE cells, even though the levels varied. No qualitative or quantitative difference were observed in the mRNA expression level of 34 (94%) of the cytokines or receptors between IPE and RPE. In contrast, the mRNA expression level of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 [VEGF-RS (FLK-1)] was lower in IPE than in RPE cells. As an increased expression of VEGF in the RPE in maculae with age-related macular disease could be involved in its pathogenesis, a decreased expression of angiogenic growth factors in IPE cells could possibly be beneficial for the therapy of age-related maculopathy if indeed other tasks of non-functional RPE cells could be performed by IPE cells. The similarity of the mRNA expression pattern in 94% of the cytokines analyzed supports the assumption that IPE cells potentially can perform functions of RPE cells in the appropriate environment. PMID:9733590

  19. 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 ?A3/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 ?A3/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 ?A3/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

  20. Stem cells as source for retinal pigment epithelium transplantation.

    PubMed

    Bertolotti, Evelina; Neri, Alberto; Camparini, Monica; Macaluso, Claudio; Marigo, Valeria

    2014-09-01

    Inherited maculopathies, age related macular degeneration and some forms of retinitis pigmentosa are associated with impaired function or loss of the retinal pigment epithelium (RPE). Among potential treatments, transplantation approaches are particularly promising. The arrangement of RPE cells in a well-defined tissue layer makes the RPE amenable to cell or tissue sheet transplantation. Different cell sources have been suggested for RPE transplantation but the development of a clinical protocol faces several obstacles. The source should provide a sufficient number of cells to at least recover the macula area. Secondly, cells should be plastic enough to be able to integrate in the host tissue. Tissue sheets should be considered as well, but the substrate on which RPE cells are cultured needs to be carefully evaluated. Immunogenicity can also be an obstacle for effective transplantation as well as tumorigenicity of not fully differentiated cells. Finally, ethical concerns may represent drawbacks when embryo-derived cells are proposed for RPE transplantation. Here we discuss different cell sources that became available in recent years and their different properties. We also present data on a new source of human RPE. We provide a protocol for RPE differentiation of retinal stem cells derived from adult ciliary bodies of post-mortem donors. We show molecular characterization of the invitro differentiated RPE tissue and demonstrate its functionality based on a phagocytosis assay. This new source may provide tissue for allogenic transplantation based on best matches through histocompatibility testing. PMID:24933042

  1. 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.

  2. 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 M, 40 M, and 80 M. 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

  3. Effect of curcumin on aging retinal pigment epithelial cells.

    PubMed

    Zhu, Wei; Wu, Yan; Meng, Yi-Fang; Wang, Jin-Yu; Xu, Ming; Tao, Jian-Jun; Lu, Jiong

    2015-01-01

    Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population. The antioxidative effects of curcumin on aging retinal pigment epithelial (RPE) cells are still unclear. We conducted an in vitro study to investigate the effects of curcumin on aging RPE cells. A pulsed H2O2 exposure aging model was adopted. Aging RPE cells were treated with curcumin 20 M, 40 M, and 80 M. 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

  4. 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

  5. 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

  6. Acute Retinal Pigment Epitheliitis: Spectral Domain Optical Coherence Tomography, Fluorescein Angiography, and Autofluorescence Findings

    PubMed Central

    Aydo?an, Tu?ba; Gney, Esra; Akay, Betl ?lkay Sezgin; Bozkurt, Tahir Kansu; nl, 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

  7. 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

  8. Estimated Cases of Blindness and Visual Impairment from Neovascular Age-Related Macular Degeneration Avoided in Australia by Ranibizumab Treatment

    PubMed Central

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

    2014-01-01

    Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14 634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 7074%). Ranibizumab given as needed would reduce incident blindness by 68% (6471%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (3439%) with monthly intravitreal ranibizumab, and by 28% (2333%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration. PMID:24979237

  9. Evaluation of the Macular, Peripapillary Nerve Fiber Layer and Choroid Thickness Changes in Behet's Disease with Spectral-Domain OCT

    PubMed Central

    Ata?, Mustafa; Yuvac?, ?sa; Demircan, Sleyman; Gler, Emel; Altunel, Orhan; Pangal, Emine; Gkta?, Altan; Stbeyaz, Serap; Zarars?z, Gkmen

    2014-01-01

    Purpose. To assess the macular, choroid, and peripapillary nerve fiber layer thickness (RNFL) in Behet's disease (BD) patients with and without ocular involvement by means of optical coherence tomography (OCT) and compare these findings with healthy controls. Design. Eighty patients with BD and 40 healthy controls who were followed up at the Uveitis and Retina Clinic of the Kayseri Research and Education Hospital in Turkey were enrolled in this prospective study. Subjects and Controls. The patients with BD were divided into two groups according to the presence of ocular involvement. Group 1 consisted of 40 eyes of 40 patients with ocular involvement and group 2 consisted of 40 eyes of 40 patients without ocular involvement. Methods. All of the patients and controls underwent macular, choroid, and peripapillary nerve fiber layer thickness analysis with Spectralis domain OCT (Spectralis OCT Heidelberg Engineering, Dossenheim, Germany). Main Outcome Measures. The differences in macular, choroid, and peripapillary nerve fiber layer thicknesses between groups were analyzed statistically. Results. Macular thickness was thinner in patients with BD than in the control group; this result was statistically significant (P = 0.05). There was no statistically significant difference in thickness between RNFL analysis of the patients with BD and control subjects. However, the BD patients with ocular involvement had statistically significant thinning in RNFL compared with BD patients without ocular involvement. Although the choroid was thicker in patients with BD than in the control group, it did not reach a statistically significant level (P = 0.382). Conclusions. BD with ocular involvement may be associated with decreased macular and RNFL thickness measured with spectral-domain OCT. PMID:24868459

  10. 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

  11. Induced pigmentation in zooplankton: a trade-off between threats from predation and ultraviolet radiation.

    PubMed

    Hansson, L A

    2000-11-22

    Ultraviolet (UV) radiation is harmful to all life, and the ongoing depletion of the ozone layer is likely to affect interactions among both terrestrial and aquatic organisms. Some organisms have evolved adaptations to reduce radiation damage, such as the various types of protective pigmentation of freshwater zooplankton. However, strong pigmentation also increases vulnerability to visually hunting predators. Hence, where both UV radiation and predation are intense, zooplankton may be sandwiched between conflicting selective pressures: to be pigmented and to be transparent at the same time. Here, I show that the level of pigmentation in copepods is up to ten times higher in lakes without predatory fishes than where fishes are present. Moreover, animals from the same population exposed to either UV light or predator scent showed a 10% difference in pigmentation after only four days, suggesting that pigmentation is an inducible trait. Hence, individual copepods are not passive victims of selective predation or radiation damage, but adjust the level of pigmentation according to the prevailing threat. The ability to adjust pigmentation level rapidly may be especially useful in situations where risk assessment is difficult due to strong seasonal and spatial variation in risk variables, such as in Arctic regions. With progressive thinning of the ozone layer, the ability of some but not other organisms to adjust protection against UV radiation may lead to counter-intuitive, large-scale alterations in freshwater food webs. PMID:11413651

  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. The ascidian pigmented sensory organs: structures and developmental programs.

    PubMed

    Esposito, R; Racioppi, C; Pezzotti, M R; Branno, M; Locascio, A; Ristoratore, F; Spagnuolo, A

    2015-01-01

    The recent advances on ascidian pigment sensory organ development and function represent a fascinating platform to get insight on the basic programs of chordate eye formation. This review aims to summarize current knowledge, at the structural and molecular levels, on the two main building blocks of ascidian light sensory organ, i.e. pigment cells and photoreceptor cells. The unique features of these structures (e.g., simplicity and well characterized cell lineage) are indeed making it possible to dissect the developmental programs at single cell resolution and will soon provide a panel of molecular tools to be exploited for a deep developmental and comparative-evolutionary analysis. PMID:25382437

  14. 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.

  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. Age-related macular degeneration: experimental and emerging treatments

    PubMed Central

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

    2009-01-01

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

  17. 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

  18. 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??g/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

  19. 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.

  20. 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 M) 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 M), 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 M), 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 M) 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

  1. A novel proteotoxic stress associated mechanism for macular corneal dystrophy.

    PubMed

    Kaarniranta, Kai; Szalai, Eszter; Smedowski, Adrian; Hegyi, Zoltn; Kivinen, Niko; Viiri, Johanna; Wowra, Bogumil; Dobrowolski, Dariusz; Mdis, Lszl; Berta, Andrs; Wylegala, Edward; Felszeghy, Szabolcs

    2015-08-01

    Macular corneal dystrophy is a rare autosomal recessive eye disease affecting primarily the corneal stroma. Abnormal accumulation of proteoglycan aggregates has been observed intra- and extracellularly in the stromal layer. In addition to the stromal keratocytes and corneal lamellae, deposits are also present in the basal epithelial cells, endothelial cells and Descemet's membrane. Misfolding of proteins has a tendency to gather into aggregating deposits. We studied interaction of molecular chaperones and proteasomal clearance in macular dystrophy human samples and in human corneal HCE-2 epithelial cells. Seven cases of macular corneal dystrophy and four normal corneal buttons collected during corneal transplantation were examined for their expression patterns of heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62. In response to proteasome inhibition the same proteins were analyzed by western blotting. Slit-lamp examination, in vivo confocal cornea microscopy and transmission electron microscopy were used for morphological analyses. Heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62 were upregulated in both the basal corneal epithelial cells and the stromal keratocytes in macular corneal dystrophy samples that coincided with an increased expression of the same molecules under proteasome inhibition in the HCE-2 cells in vitro. We propose a novel regulatory mechanism that connects the molecular chaperone and proteasomal clearance system in the pathogenesis of macular corneal dystrophy. PMID:25597745

  2. Combined amplitude and phase criteria for evaluation of macular electroretinograms.

    PubMed

    Brodie, S E; Naidu, E M; Goncalves, J

    1992-04-01

    Focal electroretinograms (ERGs) were obtained from 35 normal eyes and 48 eyes with known macular disease using the MaculoScope stimulator-ophthalmoscope instrument. Response amplitude and phase were combined to permit interpretation of the ERG responses as two-dimensional vectors. This vector interpretation avoids statistical anomalies and distortions inherent in the use of amplitude and phase response parameters. Furthermore, the vector interpretation permits the use of the Hotelling T2 statistic for the assessment of the significance of the differences between ERG responses, providing greater statistical power than simultaneous comparison of amplitude and phase data separately. The distribution of normal responses yielded limiting normal values of 135 nV for the amplitude and -95 degrees for the phase lag of the focal ERG as recorded by the MaculoScope instrument. Significant abnormalities of the focal ERG are illustrated for cases of cilioretinal artery occlusion, Stargardt's disease, idiopathic macular hole, diabetic macular edema, and idiopathic macular dysfunction with normal fundus. This study demonstrates the potential value of the focal ERG in the demonstration of macular disease undetectable by conventional electroretinography. PMID:1584569

  3. 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

  4. Holographic films from carotenoid pigments

    NASA Astrophysics Data System (ADS)

    Toxqui-Lpez, S.; Lecona-Snchez, J. F.; Santacruz-Vzquez, C.; Olivares-Prez, 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.

  5. 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

  6. [Acute multifocal placoid pigment epiteliopathy].

    PubMed

    Samoil?, O; C?lug?ru, D; C?lug?ru, M

    2007-01-01

    Acute multifocal placoid pigment epitheliopathy is a fairly rare disease with unknown etiology and pathogenesis, possibly a focal response to a systemic inflammatory process. We present the case of a young patient who developed bilateral placoid retinal lesions, in different stages of evolution - cicatriceal lesions of the right eye and mixed cicatriceal and active lesions of the left eye. Investigations showed old immunity to cytomegalovirus and toxoplasma. Fluorescein angiography showed the typical fluorescein pattern (hypoflurecence in early phases and hyperfluorescence in late phases). The case is unique because of the atypical findings: choroidal neovascularization in the left eye (rarely occurs in acute multifocal placoid pigment epitheliopathy but more commonly in serpiginous choroidopathy), recurrences, asymmetry between the two eyes (at the time of investigations visual acuity is markedly depressed in the right eye - 1/10 and the left macula is threatened by the choroidal neovascularization). PMID:18543673

  7. 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 examplesnutritional 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

  8. Human skin pigmentation, migration and disease susceptibility.

    PubMed

    Jablonski, Nina G; Chaplin, George

    2012-03-19

    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 D(3). 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 D(3) 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

  9. The ultrastructure of preretinal macular fibrosis.

    PubMed

    Rentsch, F J

    1977-09-28

    A case of preretinal macular fibrosis, following long-standing central vein occlusion and hemorrhagic glaucoma, was examined macroscopically and electron-microscopically. Pretreatment with cyclodiathermy puncture was performed twice before enucleation. The following morphologic results were observed: 1. Epiretinal cell layers in the peripapillar and foveolar regions which caused no 'puckering' of the retinal surface. These cell layers were mainly composed of glial cells. Some Mller cell processes and macrophages were also present. The epiretinal glial cells stem from the surface of the papilla and of the retina. They leave the retina through breaks of the basal lamina (especially where the latter is only a thin layer). 2. Folding (puckering) of the retinal surface was exclusively observed under condensed masses of fibrous tissue. The epiretinal fibrous tissue is composed of immature collagen fibrils of various diameters, of acid glycosaminoglycans, and of granular deposits of long-spacing collagen. The fibrillar material is firmly attached to the basal lamina of the retina. Shrinkage of the epiretinal fibrous tissue similar to the shrinkage of scar tissue is assumed to be the reason for the development of traction to the retinal surface. The epiretinal glial cells are assumed to be the sites of synthesis of the preretinal fibrous masses and glycosaminoglycans. PMID:303477

  10. Partial posterior hyaloidectomy for macular disorders

    PubMed Central

    Kim, J H; Kang, S W; Kim, Y T; Kim, S J; Chung, S E

    2013-01-01

    Purpose To evaluate the effect of partial posterior hyaloidectomy (PPH) in preventing iatrogenic retinal breaks related to the induction of a posterior vitreous detachment (IPVD) Methods Fifty-nine patients who necessitated IPVD for an epiretinal membrane or macular hole were included in this prospective, interventional case series. Extensive removal of vitreous gel, close to the retina, was conducted before IPVD under 23?G (gauge)-vitrectomy system. The PPH involved the limited extent of IPVD and limited removal of the outermost vitreous cortex to an area slightly beyond the margin of the temporal major vascular arcade. The incidence of retinal breaks related to the surgery was compared with 57 eyes that had undergone conventional 23-G total vitrectomy accompanied by extensive IPVD using ?2-test. Results Patients were followed-up for a mean of 14.3 months (630 months) after the surgery. The incidence of peripheral retinal breaks after the PPH was 3.4% (2/59 eyes), which was significantly lower than that in the eyes that underwent conventional 23?G vitrectomy (15.8%, 9/57 eyes, P=0.023) for the same disorders that required an IPVD. No patient complained of postoperative floaters, postoperatively. Conclusions PPH would be an efficient procedure to prevent iatrogenic peripheral retinal breaks related to an IPVD. PMID:23743531

  11. 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

  12. 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

  13. 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.

  14. Nonneovascular Age-Related Macular Degeneration.

    PubMed

    Michels, Stephan; Garhfer, Gerhard

    2016-01-01

    The discovery of several genetic variants associated with an increased risk for age-related macular degeneration (AMD) has led to a completely new understanding of AMD. In addition to the known modifiable risk factors, genetic risk factors may also help to assess the risk to progress to nonneovascular AMD. Recently published primary studies have indicated that genetic risk analysis may be valuable in the selection of the currently available antioxidant therapy. So far, the best evidence for preventing progression to nonneovascular AMD comes from the Age-Related Eye Disease Studies (AREDS) I and II. These studies indicate that high doses of antioxidants can reduce the risk of progression to the advanced form of the disease. However, the recent evaluation of the addition of either lutein and zeaxanthin, or x03C9;-3 long-chain polyunsaturated fatty acids, or both, to the established AREDS I formulation did not significantly reduce the risk of developing advanced AMD. There is clearly a large unmet medical need for new therapeutic options for nonneovascular AMD. The modulation of the complement cascade is - despite initially disappointing outcomes obtained with blocking complement factor 5 - currently the most promising approach to the treatment of nonneovascular AMD. PMID:26502209

  15. Neovascular Age-Related Macular Degeneration.

    PubMed

    Shao, Jack; Choudhary, Maria M; Schachat, Andrew P

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe vision loss in individuals over the age of 50 years. Choroidal neovascularization (CNV) is the hallmark of 'wet' or 'exudative' AMD, and is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. Since the approval of ranibizumab in 2006, VEGF inhibitors have rapidly altered the treatment and standard of care for wet AMD. Ranibizumab, bevacizumab, and aflibercept are now the most widely used anti-VEGF agents for the treatment of wet AMD. This chapter discusses the pharmacologic properties, pharmacokinetics, safety, and efficacy of these medications, as well as revisits landmark clinical trials that establish these drugs as gold standards in care. While these medications have greatly and positively altered the way we treat AMD, there are still many economic and therapeutic limitations with our current therapy regimens. There continue to be advancements and innovations in exploring alternative and new treatment modalities, as well as combining existing treatment options to improve efficacy, and reduce cost and patient burden. PMID:26501146

  16. 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

  17. Blue light-induced inflammatory marker expression in the retinal pigment epithelium-choroid of mice and the protective effect of a yellow intraocular lens material in vivo.

    PubMed

    Narimatsu, Toshio; Negishi, Kazuno; Miyake, Seiji; Hirasawa, Manabu; Osada, Hideto; Kurihara, Toshihide; Tsubota, Kazuo; Ozawa, Yoko

    2015-03-01

    Oxidative stress in the retinal pigment epithelium (RPE) is a well-accepted pathogenic change in vision-threatening diseases such as age-related macular degeneration. One source of oxidative stress is excessive light exposure, which causes excessive activation of the visual cycle. Because short wavelength light (blue light) has more energy, it is reported to be more harmful to photoreceptor cells than the other wavelengths of light. However, the biological effect of blue light in the RPE of living animals and the protective effect of a yellow intraocular lens (IOL) material that blocks blue light is still obscure. Therefore, we compared the pathogenic effect in the RPE-choroid complexes of mice exposed to light in a box made of a clear or a yellow IOL material. We measured the level of reactive oxygen species (ROS) using 2', 7'-dichlorodihydrofluorescein diacetate, the mRNA levels of inflammatory cytokines and a macrophage marker by real-time polymerase chain reaction, and the protein level of monocyte chemotactic protein-1 (MCP-1) by ELISA. The ROS level after light exposure was suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. In parallel, all the inflammatory cytokines that we measured and a macrophage marker were also suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. Therefore, a yellow IOL material suppressed, and thus blue light exacerbated, the increase in the ROS level and inflammatory cytokine expression as well as macrophage recruitment in the RPE-choroid in vivo after light exposure. PMID:25576667

  18. Lipofuscin and N-retinylidene-N-retinylethanolamine (A2E) accumulate in retinal pigment epithelium in absence of light exposure: their origin is 11-cis-retinal.

    PubMed

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

    2012-06-22

    The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4(-/-) than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane. PMID:22570475

  19. Prohibitin as the Molecular Binding Switch in the Retinal Pigment Epithelium.

    PubMed

    Sripathi, Srinivas R; Sylvester, O'Donnell; He, Weilue; Moser, Trevor; Um, Ji-Yeon; Lamoke, Folami; Ramakrishna, Wusirika; Bernstein, Paul S; Bartoli, Manuela; Jahng, Wan Jin

    2016-02-01

    Previously, our molecular binding study showed that prohibitin interacts with phospholipids, including phosphatidylinositide and cardiolipin. Under stress conditions, prohibitin interacts with cardiolipin as a retrograde response to activate mitochondrial proliferation. The lipid-binding switch mechanism of prohibitin with phosphatidylinositol-3,4,5-triphosphate and cardiolipin may suggest the role of prohibitin effects on energy metabolism and age-related diseases. The current study examined the region-specific expressions of prohibitin with respect to the retina and retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). A detailed understanding of prohibitin binding with lipids, nucleotides, and proteins shown in the current study may suggest how molecular interactions control apoptosis and how we can intervene against the apoptotic pathway in AMD. Our data imply that decreased prohibitin in the peripheral RPE is a significant step leading to mitochondrial dysfunction that may promote AMD progression. PMID:26661103

  20. 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

  1. Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site.

    PubMed

    Liu, Hua; Ren, Jian-Guo; Cooper, William L; Hawkins, Charles E; Cowan, Mitra R; Tong, Patrick Y

    2004-04-27

    Vascular permeability plays a key role in a wide array of life-threatening and sight-threatening diseases. Vascular endothelial growth factor can increase vascular permeability. Using a model system for nonproliferative diabetic retinopathy, we found that pigment epithelium-derived factor (PEDF) effectively abated vascular endothelial growth factor-induced vascular permeability. A 44-amino acid region of PEDF was sufficient to confer the antivasopermeability activity. Additionally, we identified four amino acids (glutamate-101, isoleucine-103, leucine-112, and serine-115) critical for this activity. PEDF, or a derivative, could potentially abate or restore vision loss from diabetic macular edema. Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability. PMID:15096582

  2. 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

  3. Age-related macular degeneration: update for primary care.

    PubMed

    Fong, D S

    2000-05-15

    Age-related macular degeneration is the leading cause of severe vision loss among the elderly. In this condition, central vision is lost, but peripheral vision almost always remains intact. Affected persons rarely require canes or guide dogs. The diagnosis of age-related macular degeneration is based on symptoms and ophthalmoscopic findings, and the disease can be classified into atrophic and exudative forms. The two currently proven treatments are laser photocoagulation and photodynamic therapy, but these measures are effective in only a small fraction of eyes with the exudative form of macular degeneration. Vision rehabilitation can help patients maximize their remaining vision and adapt so that they can perform activities of daily living. Families need encouragement in providing support and helping patients adjust to being partially sighted. PMID:10839553

  4. Functional outcome of macular edema in different retinal disorders.

    PubMed

    Tomkins-Netzer, Oren; Ismetova, Filis; Bar, Asaf; Seguin-Greenstein, Sophie; Kramer, Michal; Lightman, Sue

    2015-09-01

    Macular edema accompanies many ocular pathologies, affecting visual function and is an important factor in treatment decisions and disease outcome. Though visual acuity is commonly used to evaluate patient vision it does not always provide a complete estimate of their visual abilities or reflect their own visual perception. Furthermore, different pathologies result in macular edema causing a variable effect on visual function, related to the rate of fluid accumulation and accompanying ocular changes. Use of complementary visual function tests, such as retinal contrast sensitivity on microperimetry and reading speed provide additional information that can be used to evaluate patients and assist in treatment choices. Here we explore the effect of macular edema on visual function in different retinal pathologies, namely diabetic retinopathy, retinal vein occlusion and uveitis, examine its influence on the various vision tests and discuss the factors underlying this variable response. PMID:26014685

  5. 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

  6. 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

  7. 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

  8. 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. )

  9. Treatment of cystoid macular edema with the new-generation NSAID nepafenac 0.1%

    PubMed Central

    Hariprasad, Seenu M; Akduman, Levent; Clever, Joseph A; Ober, Michael; Recchia, Franco M; Mieler, William F

    2009-01-01

    Purpose: To describe the use of nepafenac 0.1% for cystoid macular edema (CME). Methods: This was a multicenter retrospective review of 22 CME cases (20 patients) treated with nepafenac 0.1% (six with concomitant prednisolone acetate 1%) from December 2005 to April 2008: three acute pseudophakic CME cases, 13 chronic/recalcitrant pseudophakic CME cases, and six cases of uveitic CME. Pre- and post-treatment retinal thickness and visual acuity were reported. Results: Following treatment for six weeks to six months, six eyes with uveitic CME showed a mean retinal thickness improvement of 227 168.1 ?m; mean best-corrected visual acuity (BCVA) improvement was 0.36 0.20 logMAR. All three cases of acute pseudophakic CME improved after four to 10 weeks of nepafenac, with a mean improvement in retinal thickness of 134 111.0 ?m. BCVA improved in two patients (0.16 and 0.22 logMAR) but not in the third due to underlying retinal pigment epithelium changes. Thirteen eyes with chronic/recalcitrant pseudophakic CME demonstrated a mean improvement in retinal thickness of 178 128.7 ?m after nepafenac and mean BCVA improvement of 0.33 0.19 logMAR. Conclusion: The positive outcomes of these 22 eyes strongly suggest that nepafenac 0.1% is a promising drug for the treatment of CME. Additional study under randomized controlled conditions is warranted. PMID:19668559

  10. Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model

    PubMed Central

    Ardeljan, Christopher P.; Ardeljan, Daniel; Abu-Asab, Mones; Chan, Chi-Chao

    2014-01-01

    The etiology of Age-related Macular Degeneration (AMD) remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscopeparticularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death. PMID:25580276

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

    PubMed Central

    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

  12. Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

    PubMed Central

    Curcio, Christine A.; Johnson, Mark; Huang, Jiahn-Dar; Rudolf, Martin

    2010-01-01

    The largest risk factor for age-related macular degeneration (ARMD) is advanced age. With aging, there is a striking accumulation of neutral lipids in Bruch's membrane (BrM) of normal eye that continues through adulthood. This accumulation has the potential to significantly impact the physiology of the retinal pigment epithelium (RPE). It also ultimately leads to the creation of a lipid wall at the same locations where drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD, subsequently form. Here, we summarize evidence obtained from light microscopy, ultrastructural studies, lipid histochemistry, assay of isolated lipoproteins, and gene expression analysis. These studies suggest that lipid deposition in BrM is at least partially due to accumulation of esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles produced by the RPE. Furthermore, we suggest that the formation of ARMD lesions and their aftermath may be a pathological response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (Tabas, I., K. J. Williams, and J. Born. 2007. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 116:18321844). This view provides a conceptual basis for the development of novel treatments that may benefit ARMD patients in the future. PMID:19797256

  13. 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

  14. NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

    PubMed Central

    Gao, Jiangyuan; Liu, Ruozhou Tom; Cui, Jing Z.; Matsubara, Joanne A.

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA) or choroidal neovascularization (CNV). As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity. PMID:25698849

  15. Spontaneous resolution of macular edema after silicone oil removal

    PubMed Central

    Karahan, Eyyup; Tuncer, Ibrahim; Zengin, Mehmet Ozgur; Kucukerdonmez, Cem; Kaynak, Suleyman

    2014-01-01

    AIM To investigate the macular changes in eyes filled with silicone oil (SO) and course of these changes after SO removal. METHODS A retrospective optical coherence tomography scan review was conducted for twenty-four patients who underwent uncomplicated pars plana vitrectomy with SO tamponade for complex retinal detachments were detected with optical coherence tomography before, and one week, one month and three months after SO removal. RESULTS Mean duration of SO tamponade was 3.61.0mo (range: 3-7mo). Cystoid macular edema (CME) was detected in 3 eyes before SO removal. Submacular fluid was represented in 1 eye before silicone SO removal. Resolution of CME and submacular fluid was achieved 1mo after SO removal in all eyes. Mean best corrected visual acuity (BCVA) was 1.150.65 (range, hand movement to 0.2) before SO removal in the eyes without macular changes. After SO removal, the mean BCVA values at 1wk and 1 and 3mo, and 0.820.23, 0.760.21, and 0.700.19, all of which were significantly better than baseline (P=0.030, 0.017, 0.006 respectively). In the eyes with macular CME and subretinal fluid the mean BCVA was significantly improved at 3mo after SO removal compared with baseline (P=0.037). CONCLUSION Decreased visual acuity in eyes filled with SO could be caused by macular complications due to SO. CME and subretinal fluid may resolve without any additional macular surgery after SO removal. PMID:25540755

  16. 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

  17. 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

  18. [Spontaneous detachment of the preretinal membrane in preretinal macular fibrosis].

    PubMed

    Katski, W; Oleszczy?ska-Prost, E

    1991-01-01

    Preretinal macular fibrosis is one of the most frequently encountered conditions of the macula; it is based on the formation of a transparent or white-gray preretinal membrane. Usually these changes do not progress and persist without change for many years. In rare cases it may come to a spontaneous detachment of the preretinal membrane connected usually with an improvement of the visual acuity. Presented are 2 patients with preretinal macular fibrosis in whom--after a various duration of the disease--it came to a spontaneous detachment of the preretinal membrane. PMID:1921224

  19. 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

  20. 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.

  1. 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

  2. Confirmation of persistent closure of surgically repaired macular hole in subsequent retinal detachment by optical coherence tomography.

    PubMed

    Herring, J H; Chen, C J; Chen, L L

    2000-01-01

    Idiopathic macular holes have shown response to surgical intervention with vitrectomy, presumably because of glial cell proliferation in the reapproximated tissue. We describe a patient with postoperative closure of a macular hole who subsequently developed a retinal detachment involving the macular area. Despite the detachment, the macular hole remained closed as evidenced by biomicroscopy and optical coherence tomography (OCT). OCT provides accurate documentation and assessment of pre- and postoperative conditions in macular hole surgery. PMID:10847505

  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. [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

  5. 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

  6. 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 1month 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

  7. Early postoperative macular features determined by optical coherence tomography after idiopathic macular hole surgery with silicone oil tamponade.

    PubMed

    Hotta, Kazuki

    2005-01-01

    The configuration of idiopathic macular holes in the early postoperative period after pars plana vitrectomy using optical coherence tomography through silicone oil was evaluated. Pars plana vitrectomy with internal limiting membrane peeling and silicone oil instillation was performed on 20 eyes. Optical coherence tomography images were obtained preoperatively and postoperatively. Nineteen eyes (95%) achieved a closed fovea. None of them had a transit foveal contour with flat retina without closure. In the early phase of postoperative idiopathic macular hole repair, inner retinal tissue closure rather than flattening of the fovea is essential for those undergoing pars plana vitrectomy with internal limiting membrane peeling and silicone oil instillation. PMID:16238045

  8. 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

  9. 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

  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. 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.

  12. Lipids, Lipid Genes and Incident Age-Related Macular Degeneration: The Three Continent Age-Related Macular Degeneration Consortium

    PubMed Central

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

    2014-01-01

    Purpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods Setting Three population-based cohorts. Population 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). Observation Procedures Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios (HRs) associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. Main Outcome Measures Incidence of AMD. Results The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the three studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. Conclusion In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. PMID:24879949

  13. [Damage of macular ganglion cell complex and peripapillary retinal nerve fiber layer in multiple sclerosis].

    PubMed

    Davydovskaia, M V; Tsysar', M A; Bo?ko, A N; Akopian, V S; Semenova, N S; Filonenko, I V; Fomin, A V; Gusev, E I

    2012-01-01

    The aim of this study was to evaluate macular ganglion cell complex (GCC) characteristics and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with multiple sclerosis (MS) and to investigate the associations between these parameters and clinical characteristics of patients for evaluation perspectives of using this method for monitoring of disability and neurodegenerative processes. We examined a total of 113 participants (analysis of 211 eyes), divided into three groups: 1. 48 MS patients (66 eyes) with a history of optic neuritis (ON); 2. 35 MS patients (70 eyes) without a history of ON; 3. 30 disease-free control subjects (45 eyes). The estudy included anamnesis collection, neurological examination with assessment of EDSS scores. Refracted visual acuity prior to optical coherence tomography (OCT) was tested. RTVue-100 ??? system was used to assess peripapillary RNFL thickness and macular inner parameter (protocol GCC). The strongly correlated decline of the most RNFL and GCC indices was characteristic of all groups of MS patients with and without ON compared to controls. The damage of GCC was greater in patients with ON. The inverse correlation was found between the indices studied and the level of patient's disability. The study of GCC and RNFL thickness can be used to describe and characterize the level of axonal damage in MS and for objectification of neurodegenerative process in studies on neuroprotection and neuroreparation. PMID:22677679

  14. 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

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

    PubMed

    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

  16. [Two cases of idiopathic preretinal macular fibrosis in children].

    PubMed

    Tetsumoto, K; Nakahashi, K; Tsukahara, Y; Okubo, K; Yamamoto, M

    1990-09-01

    We report herein the findings in two patients less than 15 years old with the diagnosis of idiopathic preretinal macular fibrosis, a disorder found primarily in the older population. Only a few reports have discussed idiopathic preretinal macular fibrosis in children and its pathogenesis is still unknown. One is a 10-year-old boy and the other is a 14-year-old girl who visited our hospital with a chief complaint of blurred vision in their right eyes. Epiretinal membranes were recognized on the macular region of their right eyes. Since there was no causative factors, a diagnosis of idiopathic preretinal macular fibrosis was made. They were conservatively followed up. The vision of the boy once worsened but improved spontaneously and remained stable for three years. Because the vision of the girl worsened rapidly, vitreous surgery was performed to remove the epiretinal membrane, resulting in poor vision. It was suggested that this disorder in children should be followed up conservatively and the indication of vitreous surgery should be carefully determined. PMID:2248174

  17. 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

  18. 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...

  19. 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 ?m) 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

  20. Genetics Home Reference: Age-related macular degeneration

    MedlinePLUS

    ... form. The dry form is much more common, accounting for 85 to 90 percent of all cases ... tissues. Genetic changes in and around several complement system genes, including the ... can I find information about diagnosis or management of age-related macular ...

  1. 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...

  2. 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.

  3. 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

  4. [Imaging of pigmented villonodular synovitis].

    PubMed

    Flipo, R M; Chastanet, P; Duquesnoy, B

    1993-04-01

    Pigmented villonodular synovitis is a rare disease which is usually benign but sometimes causes wide articular destruction. Since its clinical signs and symptoms are not specific, the disease may remain undiagnosed, sometimes for long periods. The diagnosis is generally confirmed at pathology, but it can now be strongly suggested by modern imaging methods. Standard radiography may be normal, with a variety of images. Arthrography with an opaque material points to the diagnosis in only two-third of the cases. Ultrasonography is non-specific. Computed tomography may be strongly suggestive of pigmented villonodular synovitis in cases with high density synovia; when coupled with arthrography, it provides detailed information on lesions of the cartilage and on extension of the synovial process. The most sensitive and specific method is magnetic resonance imaging, the most characteristic sign being low-intensity signal areas on T1- and T2-weighted sequences, corresponding to haemosiderin-loaded nodules. Performed after standard radiography, magnetic resonance imaging is the best examination method for the diagnosis and pretherapeutic evaluation of suspected villonodular synovitis. PMID:8511094

  5. Vitamin E supplementation and macular degeneration: randomised controlled trial

    PubMed Central

    Taylor, Hugh R; Tikellis, Gabriella; Robman, Luba D; McCarty, Catherine A; McNeil, John J

    2002-01-01

    Objective To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy (AMD). Design Prospective randomised placebo controlled clinical trial. Setting An urban study centre in a residential area supervised by university research staff. Participants 1193 healthy volunteers aged between 55 and 80 years; 73% completed the trial on full protocol. Interventions Vitamin E 500 IU or placebo daily for four years. Main outcome measures Primary outcome: development of early age related macular degeneration in retinal photographs. Other measures included alternative definitions of age related macular degeneration, progression, changes in component features, visual acuity, and visual function Results The incidence of early age related macular degeneration (early AMD 3) was 8.6% in those receiving vitamin E versus 8.1% in those on placebo (relative risk 1.05, 95% confidence interval 0.69 to 1.61). For late disease the incidence was 0.8% versus 0.6% (1.36, 0.67 to 2.77). Further analysis showed no consistent differences in secondary outcomes. Conclusion Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration. What is already known on this topicAge related macular degeneration is the leading cause of loss of vision and blindness in elderly people; for people aged ?90 years, two out of every three will be affected and one in four will become blindCurrently, there are no methods of prevention or treatment in most cases, though a third of cases are due to cigarette smokingAntioxidant vitamins have been suggested as a possible preventionWhat this study addsDaily supplementation with 500 mg vitamin E for four years did not alter the incidence or progression of AMD PMID:12098721

  6. Macular Surgery Using Intraoperative Spectral Domain Optical Coherence Tomography

    PubMed Central

    Riazi-Esfahani, Mohammad; Khademi, Mohammad Reza; Mazloumi, Mehdi; Khodabandeh, Alireza; Riazi-Esfahani, Hamid

    2015-01-01

    Purpose: To report the use of intraoperative spectral domain optical coherence tomography (SD-OCT) for detecting anatomical changes during macular surgery. Methods: In a consecutive case series, 32 eyes of 32 patients undergoing concurrent pars plana vitrectomy and intraoperative SD-OCT for macular hole (MH), epiretinal membrane (ERM) and vitreomacular traction (VMT) were enrolled. Intraoperative changes in retinal thickness and dimensions of the macular hole were measured in patients with ERM and VMT following surgical manipulation using a hand-held SD-OCT device (iVue, Optovue Inc., Fremont, CA, USA). Results: SD-OCT images of sixteen eyes with macular hole were subjected to quantitative and qualitative analysis. All MH dimensions remained stable during consecutive stages of surgery except for MH apex diameter, which showed a significant decrease after internal limiting membrane (ILM) peeling (P=0.025). Quantitative analysis of ten patients with ERM showed a significant decrease in retinal thickness after membrane removal (P=0.018) which did not remain significant until the end of the procedure (P=0.8). In three cases, subretinal fluid was formed after ILM peeling. Quantitative analysis of five patients with VMT showed a decrease in retinal thickness during consecutive steps of the surgery, although these changes were not significant. In two cases, subretinal fluid was formed after ILM peeling. Conclusion: Intraoperative SD-OCT is a useful imaging technique which provides vitreoretinal surgeons with rapid awareness of changes in macular anatomy during surgery and may therefore result in better anatomical and visual outcomes.

  7. 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

  8. [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

  9. 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...

  10. Pigmentation and Acriflavine Resistance in Serratia marcescens

    PubMed Central

    Woods, D. R.; Mosmann, T. R.; Hanson, Sally; Hendry, D. A.

    1971-01-01

    Stable, orange, acriflavine-resistant variants were selected by treatment of a wild-type, red, acriflavine-sensitive strain of Serratia marcescens with acriflavine. Visible, ultraviolet, infrared, and nuclear magnetic resonance spectra of purified pigment from the red strain were identical to those of the pigment from the orange strain, and the orange mutant was not due to a mutation affecting the structure of the pigment, prodigiosin. The color of the red strain was not affected by variations in pH between 5.0 and 8.0, whereas the color of the orange mutant changed from pink to orange over the same pH range. This variation was mimicked by the pH-induced variation in color of prodigiosin purified from either the red, wild-type or the orange, mutant strains. Density-gradient centrifugation of cell fragments after ultrasonic disintegration resulted in characteristic pigmented bands. Biochemical characterization of these pigmented bands showed that they contained pigment and a protein component, but no lipids, polysaccharides, sugars, glucosamine, or phosphates were detected. Further fractionation of these pigmented bands by zone electrophoresis on a sucrose density gradient indicated that some pigment in S. marcescens was specifically attached to protein components. Images PMID:4942763

  11. 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)

  12. Pigment Effector Cells in a Cnidarian.

    PubMed

    Mackie, G O

    1962-08-31

    Chromatophore complexes are described in the siphonophore Nanomia cara. The dispersion and concentration of pigment are related to variation in light intensity and do not appear to be endogenously influenced. The pigment, possibly an ommochrome, has an absorption maximum at 465 to 470 mmicro. PMID:17770957

  13. 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

  14. 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

  15. 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

  16. 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

  17. Bilateral pigmented villonodular synovitis of the knee.

    PubMed

    Shah, Samir H; Porrino, Jack A; Green, John R; Chew, Felix S

    2015-12-01

    Pigmented villonodular synovitis is a disorder resulting in a villous, nodular, or villonodular proliferation of the synovium, with pigmentation related to the presence of hemosiderin. These lesions are almost exclusively benign with rare reports of malignancy. Pigmented villonodular synovitis can occur in a variety of joints and at any age but most often occurs within the knee in the young adult. Pigmented villonodular synovitis is a rare disease entity, and bilateral synchronous or metachronous involvement of a joint is even more uncommon, with few reports previously described in the literature. We present a case of pigmented villonodular synovitis involving both the right and left knee in the same patient, with radiographic imaging, magnetic resonance imaging, photograph and video intraoperative imaging, and pathologic correlation. PMID:26649121

  18. 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

  19. 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

  20. Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment Epithelium Cells.

    PubMed

    Merl-Pham, Juliane; Gruhn, Fabian; Hauck, Stefanie M

    2016-01-01

    Age-related macular degeneration (AMD) is a medical condition usually affecting older adults and resulting in a loss of vision in the macula, the center of the visual field. The dry form of this disease presents with atrophy of the retinal pigment epithelium, resulting in the detachment of the retina and loss of photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases the risk of developing the disease by three times. In order to understand the influence of cigarette smoke on retinal pigment epithelial cells, cultured human ARPE-19 cells were treated with cigarette smoke extract for 24h. Using quantitative mass spectrometry more than 3000 proteins were identified and their respective abundances were compared between cigarette smoke-treated and untreated cells. Altogether 1932 proteins were quantified with at least two unique peptides, with 686 proteins found to be significantly differentially abundant with p>0.05. Of these proteins the abundance of 64 proteins was at least 2-fold down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up-regulated. The analysis of associated biological processes revealed an alteration of proteins involved in RNA processing and transport as well as extracellular matrix remodelling in response to cigarette smoke treatment. PMID:26427490

  1. Effect of Adding Oral Calcium Dobesilate to Laser Photocoagulation on the Macular Thickness in Patients with Diabetic Macular Edema: A Randomized Clinical Trial

    PubMed Central

    Feghhi, Mostafa; Farrahi, Fereydoun; Abbaspour, Mohammadreza; Takhtaeian, Akbar

    2014-01-01

    Purpose: To evaluate the effect of oral calcium dobesilate (Doxium) on macular thickness in clinically significant macular edema (CSME). Methods: Overall, 71 eyes of 40 patients with non-proliferative diabetic retinopathy and clinically significant macular edema were included. All patients were received laser treatment for macular edema. Coherence optical tomography was used to determine the retinal thickness. Patients were randomized into two groups: group A received three Doxium capsule daily and group B received three placebo capsule daily for six months. Results: The mean macular thickness before and after treatment in the group A was 340 and 257 micrometers respectively (24.5% reduced), and in the group B was 336 micrometers and 263 micrometers respectively (21.5% reduced). Macular thickness significantly decreased after treatment in both groups and the reduction in group A is higher but the difference of reduction between the two groups was not statistically significant (P>0.05). Conclusion: In respect to the effect of adding oral Doxium to Laser Photocoagulation on the macular thickness in patients with diabetic macular edema, this study showed no statistically significant difference between Doxium and placebo. PMID:25436194

  2. 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

    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

  3. 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

  4. 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 RPEparticularly subconfluent cellsrelative 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

  5. Diabetic macular edema: new concepts in patho-physiology and treatment

    PubMed Central

    2014-01-01

    Diabetic macular edema (DME), a serious eye complication caused primarily by hyperglycemia, is one of the major causes of blindness. DME, which is characterized by cystic retinal thickening or lipid deposition, is prone to relapse after successful treatment. DME is a complex pathological process caused by multiple factors, including breakdown of the inner and outer blood-retinal barriers, oxidative stress, and elevated levels of vascular endothelial growth factor which have been demonstrated in both preclinical and clinical studies. Starling’s law theory explains many of the features of DME. Early detection and treatment of DME can prevent vision loss. Current effective interventions for DME include treatment of systemic risk factors, such as elevated blood glucose, blood pressure and dyslipidemia. Ophthalmic treatments include laser photocoagulation, surgery and intraocular pharmacotherapy. New drugs, which are given by intraocular injection, have emerged in recent years to become first line treatment for DME that affects the central macula with loss of vision. Laser photocoagulation is still the gold standard of treatment for DME which does not involve the central macular. This review outlines these new treatments with particular emphasis on the optimal timing of how they are given. PMID:24955234

  6. 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

  7. 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 p