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Age-related Macular Degeneration (age-related + macular_degeneration)
Selected AbstractsAge-Related Macular Degeneration: Self-Management and Reduction of Depressive Symptoms in a Randomized, Controlled StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2006Barbara L. Brody MPH OBJECTIVES: To assess the effectiveness of a self-management program for age-related macular degeneration (AMD) in reducing depressive symptoms. DESIGN: Analysis of 6-month follow-up for a subset of participants in a randomized, controlled trial who were clinically depressed at baseline. SETTING: University ophthalmology clinic. PARTICIPANTS: Thirty-two depressed older adult volunteers (mean age 81.5) with advanced AMD who had been randomized to a self-management program (n=12) or one of two control conditions (n=20). Subjects were included if at baseline they met criteria from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis, I, Fourth Edition, Research Version, for major or minor depressive disorder with significant depressive symptoms (,5 points) on the 15-item Geriatric Depression Scale (GDS-15). INTERVENTION: AMD self-management program consisting of cognitive and behavioral elements including health education and enhancement of problem-solving skills. MEASUREMENTS: Primary outcome measure was GDS-15. Secondary outcome measures included National Eye Institute Visual Function Questionnaire (NEI-VFQ) and AMD Self-Efficacy Questionnaire. RESULTS: At 6-month follow-up, the self-management group had a significantly greater reduction in depressive symptoms on the GDS-15 than the controls (P=.03). The mean reduction of 2.92 points in the self-management group was more than the 2-point change threshold considered to be clinically meaningful. Change on the NEI-VFQ was nonsignificant. Reduction in depressive symptoms was associated with greater self-efficacy in the self-management group. CONCLUSION: These findings may support the effectiveness of an AMD self-management program for depressed older adults with advanced vision loss from AMD. [source] Spectral domain OCT of exudative AMDACTA OPHTHALMOLOGICA, Issue 2009N LEVEZIEL Age-related Macular Degeneration (AMD) is the main cause of vision loss in developed countries. Spectral domain OCT (SD-OCT) is a non invasive technique providing in vivo imaging of the retina, with a higher resolution than time domain OCT. This SIS will describe the clinical features of exudative AMD with SD-OCT, including occult choroidal neovascularization (CNV), classic CNV, idiopathic polypoïdal vasculopathy, and chorioretinal anastomosis. The improvement of the resolution of retinal imaging will provide a better classification and explanation of the pathological processes observed during AMD. [source] Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His,HUMAN MUTATION, Issue 9 2006Michael A. Grassi Abstract Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in the developed world. Previous studies have demonstrated that the c.1204T>C, p.Tyr402His allelic variant in the complement factor H (CFH) gene is associated with an approximately three-fold increased risk for AMD in Caucasians of predominantly European descent. Both the prevalence as well as the phenotypic spectrum of AMD varies widely among persons of different ethnicities. We hypothesized that populations with a lower prevalence of AMD might also have a lower prevalence of the CFH risk allele. In this study we sought to determine the frequency of this sequence variant in control populations of Caucasians, African Americans, Hispanics, Somalis, and Japanese. Normal control populations were assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African American (n=75), Hispanic (n=81), and Japanese (n=82). Individuals were genotyped using a restriction digest assay and the frequency of the C allele at nucleotide position 1204 of the CFH gene was determined. A bioinformatic approach was used to identify SNPs in linkage disequilibrium with rs1061170 (c.1204T>C, p.Tyr402His) from the human haplotype map project database (HapMap) in order to validate the findings. We found widely discordant frequencies of the risk allele between some of the different ethnic groups: Japanese 0.07±0.02, Hispanics 0.17±0.03, African-Americans 0.35±0.04, Caucasians 0.34±0.03, and Somalis 0.34±0.03. Allele frequencies generated by analysis of the HapMap database were consistent with these findings. This study suggests that there are other yet unidentified genetic factors important in the pathogenesis of AMD that may mitigate the effects of c.1204T>C, p.Tyr402His variant. Hum Mutat 27(9), 921,925, 2006. © 2006 Wiley-Liss, Inc. [source] Amyloid-,(1-42) alters structure and function of retinal pigmented epithelial cellsAGING CELL, Issue 2 2009Julien Bruban Summary Age-related macular degeneration (AMD) is characterized by the formation of drusen, extracellular deposits associated with atrophy of the retinal pigmented epithelium (RPE), disturbance of the transepithelial barrier and photoreceptor death. Amyloid-, (A,) is present in drusen but its role during AMD remains unknown. This study investigated the in vitro and in vivo effects of the oligomeric form of A,(1-42) , OA,(1-42) , on RPE and found that it reduced mitochondrial redox potential and increased the production of reactive oxygen species, but did not induce apoptosis in RPE cell cultures. It also disorganized the actin cytoskeleton and halved occludin expression, markedly decreasing attachment capacity and abolishing the selectivity of RPE cell transepithelial permeability. Antioxidant pretreatment partially reversed the effects of OA,(1-42) on mitochondrial redox potential and transepithelial permeability. Subretinally injected OA,(1-42) induced pigmentation loss and RPE hypertrophy but not RPE cell apoptosis in C57BL/6 J mice. Rapid OA,(1-42)-induced disorganization of cytoskeletal actin filaments was accompanied by decreased RPE expression of the tight junction proteins occludin and zonula occludens-1 and of the visual cycle proteins cellular retinaldehyde-binding protein and RPE65. The number of photoreceptors decreased by half within a few days. Our study pinpoints the role of A, in RPE alterations and dysfunctions leading to retinal degeneration and suggests that targeting A, may help develop selective methods for treating diseases involving retinal degeneration, such as AMD. [source] Obesity, Lutein Metabolism, and Age-Related Macular Degeneration: A Web of ConnectionsNUTRITION REVIEWS, Issue 1 2005Elizabeth J. Johnson PhD Age-related macular degeneration (AMD) is a major cause of visual impairment in the United States. Currently there is no effective cure for this disease. Risk factors include decreased lutein and zeaxanthin status and obesity. Obesity is also an increasing public health concern. The alarming increase in the prevalence of obesity further exacerbates the public health concern of AMD. The mechanism by which obesity increases the risk of AMD may be related to the physiologic changes that occur with this condition. These include increased oxidative stress, changes in the lipoprotein profile, and increased inflammation. These changes would also result in an increased destruction and a decreased circulatory delivery of lutein and zeaxanthin to the macula of the eye. Therefore, the mechanism by which obesity is related to AMD risk may be through indirect effects on changes in lutein and zeaxanthin status and metabolism. [source] The Pigmentation of Human Iris Influences the Uptake and Storing of ZincPIGMENT CELL & MELANOMA RESEARCH, Issue 5 2004Despina Kokkinou Age-related macular degeneration (AMD) is more prevalent among the elderly Caucasians than in Africans. A significant association between light iris colour, fundus pigmentation and incidence of AMD is reported, suggesting a possible correlation with melanin pigment. Zinc is known to bind to melanin in pigmented tissues and to enhance antioxidant capacity by function as a cofactor or gene expression factor of antioxidant enzymes in the eye. In this in vitro study, we investigated the uptake and storage of zinc in human irides. Irides of blue and brown human eyes were used. The number of melanocytes was measured. Tissues without any treatment served as controls. The irides were incubated with 100 ,M zinc chloride in culture medium for 24 h. Specimens of the tissues were stored for the uptake examination. The remained pieces were further incubated for 3 and 7 d to investigate the storage of zinc. The concentration of zinc was measured by inductively coupled plasma mass spectrometry (ICP-MS). Melanocytes count was significantly higher in the brown tissues (P < 0.0001). Zinc concentration of blue coloured irides after 24 h zinc treatment was close to the controls. We did not observe any significant storing. In contrast, the concentration of zinc in brown irides was significantly increased after 24 h (P , 0.01) and remained at a high level for 7 d. The uptake of zinc is likely dependent on the amount of pigmentation in human iris. Therefore, we assume that in patients suffering from AMD the degree of pigmentation of the irides and eventually fundi should be under consideration when the patients are treated with zinc supplementation. [source] Analysis of Single Nucleotide Polymorphisms in the NOS2A Gene and Interaction with Smoking in Age-Related Macular DegenerationANNALS OF HUMAN GENETICS, Issue 3 2010Juan A. Ayala-Haedo Summary Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P= 0.035). A significant interaction with smoking was detected at rs2248814 (P= 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible synergistic interaction of AA genotype with smoking, although the result bears replication in larger samples. Our data suggests that SNPs in the NOS2A gene are associated with increased risk for AMD and might modulate the effect of smoking on AMD. [source] 2231: Age-related modifications in RPE cellsACTA OPHTHALMOLOGICA, Issue 2010E MANNERMAA Age-related macular degeneration (AMD) is a multi-factorial polygenetic aging disease. It has been shown that RPE dysfunction predisposes neural retinal dysfunction and the development of choroidal neovascularization. The pathogenesis of age-related macular degeneration (AMD) essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells and extracellular drusen formation, as well as the presence of chronic inflammation. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. This presence of lipofuscin decreases lysosomal enzyme activity and impairs autophagic clearance of damaged proteins which should be removed from cells. Proteasomes are another crucial proteolytic machine which degrades especially cellular proteins damaged by oxidative stress. The cross-talk between lysosomes, autophagy and proteasomes in RPE cell protein aggregation, their role as a possible therapeutic target and their involvement in the pathogenesis of AMD is discussed. In addition, age related changes in Bruch's membrane and choroidal blood flow may take part in the pathogenesis of AMD. This will be also discussed. [source] Five-year incidence of visual impairment and blindness in older Icelanders: the Reykjavik Eye StudyACTA OPHTHALMOLOGICA, Issue 3 2010Elin Gunnlaugsdottir Abstract. Purpose:, This study examined age, sex and cause-specific 5-year incidence of visual impairment and blindness in a middle-aged and elderly Icelandic population. Methods:, The study cohort consisted of a population-based, random sample of citizens aged , 50 years. Of 1379 eligible subjects, 1045 underwent a baseline examination in 1996; 846 of the 958 survivors (88.2%) underwent a 5-year follow-up examination in 2001. All participants underwent an extensive ophthalmological examination including best corrected visual acuity (BCVA) using a Snellen chart. We used World Health Organization (WHO) criteria, which define visual impairment as BCVA in the better eye of < 6/18 and , 3/60 and blindness as BCVA in the better eye of < 3/60. We also used US criteria, which consider BCVA of < 6/12 and > 6/60 in the better eye to represent visual impairment and BCVA of , 6/60 in the better eye to represent blindness. The causes of incident visual loss in either eye were determined. Deterioration or improvement in vision were defined as a loss or gain of , 2 Snellen lines. Results:, According to WHO criteria, 5-year incidence of bilateral visual impairment and blindness were 1.07% (95% confidence interval [CI] 0.37,1.76) and 0.35% (95% CI 0.00,0.76), respectively. Using US criteria, equivalent incidence of bilateral visual impairment and blindness were 3.49% (95% CI 2.24,4.74) and 0.95% (95% CI 0.29,1.60), respectively. Age-related macular degeneration and cataract were the major causes of incident visual impairment and blindness. Conclusions:, Incidences of visual impairment and blindness increased significantly with age. Age-related macular degeneration, present in 75% of affected persons, was the most common cause of 5-year incident legal blindness in this middle-aged and elderly Icelandic population. [source] Age-related macular degeneration: hemodynamic changesACTA OPHTHALMOLOGICA, Issue 2009CJ POURNARAS Purpose Metabolic changes of the RPE associated to the dysfunction of choriocapillaries(CC)/RPE complex may induces the AMD-related changes. Additional vascular changes in the choroid potentially have deleterious effects on the RPE. Methods Quantification of CC number and lumen diameters in cross sections and alkaline phosphatase (APase) flat-embedding technique, expressing high constitutive APase activity in choriocapillaris and choroidal veins on human RPE/Bruch's Membrane/CC complex, significantly contributed to the analysis of the choroidal vasculature. Laser Doppler flowmetry (LDF) data provided additional information on the assessment of hemodynamic changes in AMD. Results Choroidal vascular density reduction and significant vasoconstriction of the choriocapillaries, occurs during the evolution of AMD. In eyes with geographic atrophy, the RPE degenerates first while CC loss is secondary to RPE degeneration. In eyes with exudative AMD, degeneration of the CC layer occurs while RPE is still functional. LDF data indicated choroidal blood flow decrease according to age and the degree of severity of AMD; the decrease in flow preceding the formation of choroidal CNV, strongly suggest that these changes may have a role in the development of CNV. As a result of vascular dysfunction, the choroidal blood flow is dysregulated in patients with neovascular AMD. The choroidal watershed zone (WZ) courses through the fovea more often in patients suffering from AMD than in age-matched controls, particularly in the presence of CNV. Choroidal neovascularisation usually arises within these WZ. Conclusion The role of choroidal ischemia in the pathophysiology of AMD is supported by the observed choroidal microcirculation anatomical and fucntional abnormalities. [source] The epidemiology of age-related macular degeneration in the Indian subcontinentACTA OPHTHALMOLOGICA, Issue 3 2009Jyh Haur Woo Abstract. Context:, The Indian subcontinent is one of the most populous regions in the world. Given the projected rapid population growth and ageing of the population, age-related macular degeneration (AMD) is likely to emerge as a major public health threat in the near future. However, existing literature on AMD in the region is scarce. Methods:, This paper reviews the epidemiology and risk factors of AMD in the Indian subcontinent. Results:, Data on AMD in India show prevalences ranging from 1.8% to 4.7%. Blindness prevalence studies in Pakistan, Bangladesh and Nepal have also reported rates of 2.1% to 8.7% for all blindness attributable to AMD. Age-related macular degeneration is therefore a significant cause of visual morbidity in these countries. To date, no reliable epidemiological data on AMD or blindness have been published for Sri Lanka, Afghanistan, Maldives or Bhutan. Conclusions:, The prevalence of AMD in the region is likely to follow a trend similar to that seen in the developed world in the coming years. Eye care policies should therefore make provisions for this chronic age-related eye disease. In addition, there is an urgent need for more data on the epidemiology of AMD in the Indian subcontinent. [source] Inflammation in AMD pathologyACTA OPHTHALMOLOGICA, Issue 2008JZ NOWAK Age-related macular degeneration (AMD) is a progressive retinal disease that leads to substantial irreversible vision loss in elderly patients. Two clinical categories of AMD are distinguished: the "dry" atrophic form and the exudative neovascular or "wet" form. There is neither a preventive therapy nor a cure for both forms, although recent efforts succeeded in a more effective treatment of the wet AMD with PDT and anti-VEGF drugs. AMD is a multifactorial pathology which involves complex interaction of metabolic, genetic and environmental factors, with major biochemical-clinical abnormalities seen in four functionally interrelated tissues: photoreceptors, retinal pigment epithelium, Bruch's membrane and choriocapilaries. Four processes specifically contribute to the development of AMD pathology: lipofuscinogenesis (in RPE cells), drusogenesis (with drusen located between RPE and Bruch's membrane), inflammation (local) and choroidal neovascularization (in wet form). Although the role of immune system and inflammation has been implicated in AMD pathogenesis for many years, an impetus to intensify the research in this direction gave a recent discovery of polymorphisms in genes that encode for elements of the complement system, including factor H (CFH; Y402H), factor B, and complement component 2. An increased activity of the complement alternative pathway due to the lack of or insufficient control by CFH appears to contribute to AMD progression via immunologic mechanism which drives inflammatory response. An arising question is whether blockade of overactive complement system will be a therapeutic strategy safe for patients and effective to prevent or slowing down the macula-devastating and vision-threatening disease. Supported by grant no. 503-1023-1 from Medical University of Lodz. [source] Age-related macular degeneration and geneticsCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 1 2010Nagahisa Yoshimura MD PhD No abstract is available for this article. [source] The Y402H variant of complement factor H is associated with age-related macular degeneration but not with diabetic retinal disease in the Go-DARTS studyDIABETIC MEDICINE, Issue 5 2009A. S. F. Doney Abstract Aims, The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening. Methods, Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models. Results, The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 × 10,11). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 × 10,7). The life-time hazard ratio was 3.4 (P = 2.1 × 10,16). We found no association of Y402H with development of referable diabetic retinal disease. Conclusion, The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions. [source] Oxidative damage of retinal pigment epithelial cells and age-related macular degenerationDRUG DEVELOPMENT RESEARCH, Issue 5 2007Suofu Qin Abstract Damage to the retinal pigment epithelial (RPE) cells is an early and crucial event in the molecular pathways leading to clinically relevant age-related macular degeneration (AMD) changes. Oxidative stress, the major environmental risk factor for atrophic AMD, causes RPE injury that results in a chronic inflammatory response, drusen formation, and RPE atrophy. RPE degeneration ultimately leads to a progressive irreversible degeneration of photoreceptors. In vitro studies show that oxidant-treated RPE cells undergo apoptosis, a possible mechanism by which RPE cells are lost during the early phase of atrophic AMD. The main target of oxidative injury appears to be mitochondria, an organelle known to accumulate genomic damage during aging. Addition of GSH, the most abundant intracellular thiol antioxidant, protects RPE cells from oxidant-induced apoptosis. Similar protection occurs with dietary enzyme inducers that increase GSH synthesis. In addition, enhancing survival signaling preserves RPE cells under oxidative stress. These results indicate that therapeutic or nutritional intervention to enhance the antioxidant capacity and survival signaling of RPE may provide an effective way to prevent or treat AMD. This review describes major molecular and cellular events leading to RPE death, and presents currently used and new experimental, forthcoming therapeutic strategies. Drug Dev Res 68:213,225, 2007. © 2007 Wiley-Liss, Inc. [source] Pegaptanib sodium for age-related macular degenerationFUTURE PRESCRIBER, Issue 3 2006Phil Hykin FRCOphth, Sobha Sivaprasad FRCS [source] Testing association for markers on the X chromosome,GENETIC EPIDEMIOLOGY, Issue 8 2007Gang Zheng Abstract Test statistics for association between markers on autosomal chromosomes and a disease have been extensively studied. No research has been reported on performance of such test statistics for association on the X chromosome. With 100,000 or more single-nucleotide polymorphisms (SNPs) available for genome-wide association studies, thousands of them come from the X chromosome. The X chromosome contains rich information about population history and linkage disequilibrium. To identify X-linked marker susceptibility to a disease, it is important to study properties of various statistics that can be used to test for association on the X chromosome. In this article, we compare performance of several approaches for testing association on the X chromosome, and examine how departure from Hardy-Weinberg equilibrium would affect type I error and power of these association tests using X-linked SNPs. The results are applied to the X chromosome of Klein et al. [2005], a genome-wide association study with 100K SNPs for age-related macular degeneration. We found that a SNP (rs10521496) covered by DIAPH2, known to cause premature ovarian failure (POF) in females, is associated with age-related macular degeneration. Genet. Epidemiol. 2007. Published 2007 Wiley-Liss, Inc. [source] Interpreting analyses of continuous covariates in affected sibling pair linkage studiesGENETIC EPIDEMIOLOGY, Issue 6 2007Silke Schmidt Abstract Datasets collected for linkage analyses of complex human diseases often include a number of clinical or environmental covariates. In this study, we evaluated the performance of three linkage analysis methods when the relationship between continuous covariates and disease risk or linkage heterogeneity was modeled in three different ways: (1) The covariate distribution is determined by a quantitative trait locus (QTL), which contributes indirectly to the disease risk; (2) the covariate is not genetically determined, but influences the disease risk through statistical interaction with a disease susceptibility locus; (3) the covariate distribution differs in families linked or unlinked to a particular disease susceptibility locus. We analyzed simulated datasets with a regression-based QTL analysis, a nonparametric analysis of the binary affection status, and the ordered subset analysis (OSA). We found that a significant OSA result may be due to a gene that influences variability in the population distribution of a continuous disease risk factor. Conversely, a regression-based QTL analysis may detect the presence of gene-environment (G × E) interaction in a sample of primarily affected individuals. The contribution of unaffected siblings and the size of baseline lod scores may help distinguish between QTL and G × E models. As illustrated by a linkage study of multiplex families with age-related macular degeneration, our findings assist in the interpretation of analysis results in real datasets. They suggest that the side-by-side evaluation of OSA and QTL results may provide important information about the relationship of measured covariates with either disease risk or linkage heterogeneity. Genet. Epidemiol. 2007. © 2007 Wiley-Liss, Inc. [source] Case,control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD),HUMAN MUTATION, Issue 4 2007Sheila A. Fisher Abstract This article reports a well-powered age-related macular degeneration (AMD) case,control association study in the HMCN1 gene, showing that common variants do not account for a substantial proportion of AMD cases. Thus, the consistent linkage peak observed by several genome-wide linkage scans within the 1q32 region is unlikely to be attributed to polymorphisms at the HMCN1 locus. In addition, the analysis provides comprehensive data suggesting that low-frequency variants encoding possible functional amino acid polymorphisms in the HMCN1 gene may not contribute substantially to disease, although HMCN1 mutations may still confer disease susceptibility in a small subset of patients. Interestingly, the HMCN1 p.Gln5346Arg mutation, which is thought to be a causal mutation in a large AMD pedigree segregating the disease as a single-gene trait, appears to occur in our control cohort as a low-frequency polymorphism with an allele frequency of approximately 0.0026. Hum Mutat 28(4), 406,413, 2007. © 2007 Wiley-Liss, Inc. [source] Dip-Pen Nanolithography of Bioactive Peptides on Collagen-Terminated Retinal Membrane,ADVANCED MATERIALS, Issue 19 2008Rizaldi Sistiabudi Dip-pen nanolithography is used to directly modify freshly dissected eye tissues with biologically active collagen-binding peptide molecules. The results address the challenge of surface heterogeneity and utilize dip-pen nanolithography to control the localization and concentration of molecules on a collagen-terminated tissue-derived surface. This method can allow the development of scaffolds for treatment of age-related macular degeneration. [source] Age-Related Macular Degeneration: Self-Management and Reduction of Depressive Symptoms in a Randomized, Controlled StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2006Barbara L. Brody MPH OBJECTIVES: To assess the effectiveness of a self-management program for age-related macular degeneration (AMD) in reducing depressive symptoms. DESIGN: Analysis of 6-month follow-up for a subset of participants in a randomized, controlled trial who were clinically depressed at baseline. SETTING: University ophthalmology clinic. PARTICIPANTS: Thirty-two depressed older adult volunteers (mean age 81.5) with advanced AMD who had been randomized to a self-management program (n=12) or one of two control conditions (n=20). Subjects were included if at baseline they met criteria from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis, I, Fourth Edition, Research Version, for major or minor depressive disorder with significant depressive symptoms (,5 points) on the 15-item Geriatric Depression Scale (GDS-15). INTERVENTION: AMD self-management program consisting of cognitive and behavioral elements including health education and enhancement of problem-solving skills. MEASUREMENTS: Primary outcome measure was GDS-15. Secondary outcome measures included National Eye Institute Visual Function Questionnaire (NEI-VFQ) and AMD Self-Efficacy Questionnaire. RESULTS: At 6-month follow-up, the self-management group had a significantly greater reduction in depressive symptoms on the GDS-15 than the controls (P=.03). The mean reduction of 2.92 points in the self-management group was more than the 2-point change threshold considered to be clinically meaningful. Change on the NEI-VFQ was nonsignificant. Reduction in depressive symptoms was associated with greater self-efficacy in the self-management group. CONCLUSION: These findings may support the effectiveness of an AMD self-management program for depressed older adults with advanced vision loss from AMD. [source] Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cellsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Tuomas Ryhänen Abstract The pathogenesis of age-related macular degeneration involves chronic oxidative stress, impaired degradation of membranous discs shed from photoreceptor outer segments and accumulation of lysosomal lipofuscin in retinal pigment epithelial (RPE) cells. It has been estimated that a major part of cellular proteolysis occurs in proteasomes, but the importance of proteasomes and the other proteolytic pathways including autophagy in RPE cells is poorly understood. Prior to proteolysis, heat shock proteins (Hsps), agents that function as molecular chaperones, attempt to refold misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. In the present study, the roles of the Hsp70 molecular chaperone and proteasomal and lysosomal proteolytic pathways were evaluated in human RPE cells (ARPE-19). The Hsp70 and ubiquitin protein levels and localization were analysed by Western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. Hsp70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. The proteasome inhibitor MG-132 evoked the accumulation of perinuclear aggregates positive for Hsp70, ubiquitin-protein conjugates and the lysosomal membrane protein LAMP-2. Interestingly, the hsp70 mRNA depletion significantly increased cell death in conjunction with proteasome inhibition. We found that the accumulation of lysosomes was reversible: a cessation of proteasome inhibition led to clearance of the deposits via a mechanism believed to include autophagy. The molecular chaperone Hsp70, proteasomes and autophagy have an important regulatory role in the protein turnover of human RPE cells and may thus open new avenues for understanding degenerative processes in retinal cells. [source] Age-related reduction in retinal deimination levels in the F344BN ratAGING CELL, Issue 3 2008Sanjoy K. Bhattacharya Summary Increased deimination and peptidyl arginine deiminase type 2 (PAD2) expression has been observed in age-related neurodegenerative diseases without discrimination between their aging and disease component. Here, we describe reduced levels of deimination commensurate with reduced protein, mRNA and activity of peptidylarginine deiminase type 2 in the retina, optic nerve and plasma of aged rats when compared to young rats. The decrease was significant in the ganglion cell layer, inner plexiform layer and inner nuclear layer. Because our observations suggest reduced deimination is a consequence of aging, we conclude that increased deimination must be a consequence of disease. Our findings are important to understand late-onset and progressive diseases such as glaucoma, pseudoexfoliation syndrome, age-related macular degeneration and Oguchi's disease. [source] Increased expression of glial cell line-derived neurotrophic factor protects against oxidative damage-induced retinal degenerationJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Aling Dong Abstract Oxidative damage contributes to retinal cell death in patients with age-related macular degeneration or retinitis pigmentosa. One approach to treatment is to identify and eliminate the sources of oxidative damage. Another approach is to identify treatments that protect cells from multiple sources of oxidative damage. In this study, we investigated the effect of increased expression of glial cell line-derived neurotrophic factor (GDNF) in three models of oxidative damage-induced retinal degeneration. Double transgenic mice with doxycycline-inducible expression of GDNF in the retina were exposed to paraquat, FeSO4, or hyperoxia, all sources of oxidative damage and retinal cell death. Compared to controls, mice with increased expression of GDNF in the retina showed significant preservation of retinal function measured by electroretinograms, reduced thinning of retinal cell layers, and fewer TUNEL-positive cells indicating less retinal cell death. Mice over-expressing GDNF also showed less staining for acrolein, nitrotyrosine, and 8-hydroxydeoxyguanosine, indicating less oxidative damage to lipids, proteins, and DNA. This suggests that GDNF did not act solely to allow cells to tolerate higher levels of oxidative damage before initiation of apoptosis, but also reduced damage from oxidative stress to critical macromolecules. These data suggest that gene transfer of Gdnf should be considered as a component of therapy for retinal degenerations in which oxidative damage plays a role. [source] Effects of lutein and zeaxanthin on aspects of eye healthJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 1 2010Le Ma Abstract Lutein and zeaxanthin are members of the oxygenated carotenoids found particularly in egg yolks and dark-green leafy vegetables. A great deal of research has focused on their beneficial roles in eye health. The present article summarises the current literature related to the bioactivity of these carotenoids, emphasising their effects and possible mechanisms of action in relation to human eye health. Available evidence demonstrates that lutein and zeaxanthin are widely distributed in a number of body tissues and are uniquely concentrated in the retina and lens, indicating that each has a possible specific function in these two vital ocular tissues. Most of epidemiological studies and clinical trials support the notion that lutein and zeaxanthin have a potential role in the prevention and treatment of certain eye diseases such as age-related macular degeneration, cataract and retinitis pigmentosa. The biological mechanisms for the protective effects of these carotenoids may include powerful blue-light filtering activities and antioxidant properties. Although most studies point towards significant health benefits from lutein and zeaxanthin, further large-scale randomised supplementation trials are needed to define their effects on ocular function in health and disease. Copyright © 2009 Society of Chemical Industry [source] Custom-devised and generic digital enhancement of images for people with maculopathyOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 4 2009Susan J. Leat Abstract Aim:, The purpose of this study was to compare the effectivity, in terms of the potential usefulness, of digital filters based on either contrast sensitivity (CS) or supra-threshold contrast matching (CM) in enhancing pictures images for people with maculopathy and to investigate whether generic filters (not based on an individual's vision loss) are equally as effective. Effectivity is measured by changes in perceived visibility. Methods:, Thirty-five subjects with maculopathy, aged 20,92 years, took part [13 atrophic age-related macular degeneration (ARMD), 14 exudative ARMD, and 8 juvenile macular dystrophy (JMD)]. CS and supra-threshold CM were measured. A range of CS filters (1 or 2-octave wide band-pass filter using a Gabor or polynomial envelope) with different strengths were developed based on the ratio of the individual's contrast threshold and that of a normal age-related group. Similarly filters were developed based on CM at 3.6% and 27.9% contrast. The following generic filters were also applied with different ,strengths': edge enhancement; sharpening; contrast enhancement; Peli's adaptive enhancement; difference of Gaussian; and an equi-emphasis band-pass filter. The filters were applied to images of faces and general scenes. Subjects were asked to rank the perceived visibility of images (to obtain the best version of each filter) and then to rate the perceived visibility of each image filtered with a particular filter. Results:, In general, subjects with atrophic ARMD and JMD preferred the weaker versions of most of the filters, while those with exudative ARMD did not show such a clear preference. Generally, images of faces were preferred with less enhancement than scenes. The filters based on CM were rated as giving significant improvement, while those based on CS and peak emphasis were not preferred. Of the generic filters, the Peli adaptive enhancement filter was most frequently rated as giving a significant improvement (p < 0.05) followed by the contrast enhancement filter. They gave the same perceived enhancement as the custom-devised filters. Conclusions:, Generic filters, which are easier to apply than the custom-devised filters, are appropriate for rehabilitation purposes. [source] The Neovessel Occlusion Efficacy of 151 -Hydroxypurpurin-7-Lactone Dimethyl Ester Induced with Photodynamic TherapyPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2010Siang Hui Lim In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 151 -hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 ,L volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 ,g per embryo of G2 and a light dose of 20 J cm,2 at a fluence rate of 40 mW cm,2 filtered at 400,440 nm,a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light,an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer. [source] OT-674 Suppresses Photooxidative Processes Initiated by an RPE Lipofuscin FluorophorePHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2008Jilin Zhou The pathological processes involved in age-related macular degeneration (AMD) include retinal pigment epithelial (RPE) cell degeneration; oxidative mechanisms likely contribute to the demise of these cells. Indeed, RPE cells may be particularly susceptible to photooxidative mechanisms since they accumulate retinoid-derived photoreactive compounds that constitute the lipofuscin of the cell. Thus we undertook to test the capacity of OT-674, the reduction product (Tempol-H) of the nitroxide Tempol, to suppress photooxidative processes initiated by the RPE lipofuscin fluorophore A2E. Accordingly, when ARPE-19 cells that had accumulated A2E were irradiated at 430 nm, pretreatment with OT-674 (0.01,10 mm) was found to confer a resistance to cell death. Monitoring by quantitative HPLC also showed that OT-674 reduced A2E photooxidation in a cell-free system. Moreover, when presented with a singlet oxygen generator, OT-674 served as a quencher of singlet oxygen that was more effective than Trolox and ,-tocopherol. We conclude that OT-674 is a potent antioxidant that suppresses photooxidative processes generated in cultured RPE cells by the lipofuscin fluorophore A2E. As oxidative damage to RPE cells is considered to be a risk factor for AMD, antioxidant therapy with OT-674 may serve a protective role. [source] Retinal and Optic Nerve DiseasesARTIFICIAL ORGANS, Issue 11 2003Eyal Margalit Abstract:, A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device. [source] Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin®) in neovascular age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 6 2010Philippe Bonnin Acta Ophthalmol. 2010: 88: 641,645 Abstract. Purpose:, Angiogenic inhibitors, alone or combined with other therapies, are believed to represent a promising treatment for neovascularization in age-related macular degeneration (wet AMD). They can maintain or improve visual acuity (VA), at least for the first 2 years. However, evolution to retinal atrophy cannot be ruled out and it may be useful to assess the effects of antiangiogenic therapy on retinal and choroidal circulation. Methods:, We carried out a pilot study in 15 patients with wet AMD. Time-averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before and 4 weeks after a single intravitreal injection of 1.25 mg bevacizumab in 0.05 ml. Patients underwent two ophthalmic examinations, before and 4 weeks after injection, including VA measurement and optical coherence tomography (OCT3) examination. Results:, In treated eyes, bevacizumab injection was followed by a significant improvement in VA (from 20/125 to 20/80; p = 0.0214), and a decrease in mean central macular thickness (from 392 ± 96 ,m to 271 ± 50 ,m; p = 0.0038). Mean BFV decreased by 10% in the CRA (p = 0.0226), 20% in the TPCA (p = 0.0026) and 20% in the OA (p = 0.0003). No effect was observed in fellow eyes. Conclusions:, Intravitreal bevacizumab acutely improved VA and reduced central macular thickness in wet AMD. Ultrasound imaging revealed that BFVs decreased in all retrobulbar arteries, suggesting that after local diffusion, bevacizumab exerts a short-term regional effect. Bevacizumab might therefore induce hypoperfusion of the whole eye, which may correspond to a vascular side-effect. [source] | ||||||||||||||||