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Find video protocols related to scientific articles indexed in Pubmed.
Optical Coherence Tomography-Defined Changes Preceding the Development of Drusen-Associated Atrophy in Age-Related Macular Degeneration.
Ophthalmology
PUBLISHED: 08-08-2014
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To characterize the pathological changes preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT).
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Geographic atrophy: a histopathological assessment.
JAMA Ophthalmol
PUBLISHED: 03-15-2014
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Geographic atrophy (GA) is the major cause of blind registration in Western communities, although, with few exceptions, it is less common than choroidal neovascular disease. The variation of phenotype implies that age-related macular degeneration (AMD) does not follow the same course from one case to another and that phenotyping may be important before initiating a therapeutic trial.
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Reticular pseudodrusen: a risk factor for geographic atrophy in fellow eyes of individuals with unilateral choroidal neovascularization.
Ophthalmology
PUBLISHED: 02-08-2014
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To determine whether reticular pseudodrusen (RPD) confer an increased risk of progression to late-stage age-related macular degeneration (AMD) in fellow eyes of those recently diagnosed with unilateral choroidal neovascularization (CNV).
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Reticular macular disease is associated with multilobular geographic atrophy in age-related macular degeneration.
Retina (Philadelphia, Pa.)
PUBLISHED: 05-02-2013
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To investigate the incidence of reticular macular disease (RMD), a subphenotype of age-related macular degeneration, in multilobular geographic atrophy (GA) and its relation to GA progression.
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Temporal macular thinning associated with X-linked Alport syndrome.
JAMA Ophthalmol
PUBLISHED: 04-11-2013
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Optical coherence tomography (OCT) findings of temporal macular thinning are important in the diagnosis and prognosis of X-linked Alport syndrome (XLAS).
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Seven new loci associated with age-related macular degeneration.
Lars G Fritsche, Wei Chen, Matthew Schu, Brian L Yaspan, Yi Yu, Gudmar Thorleifsson, Donald J Zack, Satoshi Arakawa, Valentina Cipriani, Stephan Ripke, Robert P Igo, Gabriëlle H S Buitendijk, Xueling Sim, Daniel E Weeks, Robyn H Guymer, Joanna E Merriam, Peter J Francis, Gregory Hannum, Anita Agarwal, Ana Maria Armbrecht, Isabelle Audo, Tin Aung, Gaetano R Barile, Mustapha Benchaboune, Alan C Bird, Paul N Bishop, Kari E Branham, Matthew Brooks, Alexander J Brucker, William H Cade, Melinda S Cain, Peter A Campochiaro, Chi-Chao Chan, Ching-Yu Cheng, Emily Y Chew, Kimberly A Chin, Itay Chowers, David G Clayton, Radu Cojocaru, Yvette P Conley, Belinda K Cornes, Mark J Daly, Baljean Dhillon, Albert O Edwards, Evangelos Evangelou, Jesen Fagerness, Henry A Ferreyra, James S Friedman, Asbjorg Geirsdottir, Ronnie J George, Christian Gieger, Neel Gupta, Stephanie A Hagstrom, Simon P Harding, Christos Haritoglou, John R Heckenlively, Frank G Holz, Guy Hughes, John P A Ioannidis, Tatsuro Ishibashi, Peronne Joseph, Gyungah Jun, Yoichiro Kamatani, Nicholas Katsanis, Claudia N Keilhauer, Jane C Khan, Ivana K Kim, Yutaka Kiyohara, Barbara E K Klein, Ronald Klein, Jaclyn L Kovach, Igor Kozak, Clara J Lee, Kristine E Lee, Peter Lichtner, Andrew J Lotery, Thomas Meitinger, Paul Mitchell, Saddek Mohand-Saïd, Anthony T Moore, Denise J Morgan, Margaux A Morrison, Chelsea E Myers, Adam C Naj, Yusuke Nakamura, Yukinori Okada, Anton Orlin, M Carolina Ortube, Mohammad I Othman, Chris Pappas, Kyu Hyung Park, Gayle J T Pauer, Neal S Peachey, Olivier Poch, Rinki Ratna Priya, Robyn Reynolds, Andrea J Richardson, Raymond Ripp, Guenther Rudolph, Euijung Ryu, José-Alain Sahel, Debra A Schaumberg, Hendrik P N Scholl, Stephen G Schwartz, William K Scott, Humma Shahid, Haraldur Sigurdsson, Giuliana Silvestri, Theru A Sivakumaran, R Theodore Smith, Lucia Sobrin, Eric H Souied, Dwight E Stambolian, Hreinn Stefansson, Gwen M Sturgill-Short, Atsushi Takahashi, Nirubol Tosakulwong, Barbara J Truitt, Evangelia E Tsironi, André G Uitterlinden, Cornelia M van Duijn, Lingam Vijaya, Johannes R Vingerling, Eranga N Vithana, Andrew R Webster, H-Erich Wichmann, Thomas W Winkler, Tien Y Wong, Alan F Wright, Diana Zelenika, Ming Zhang, Ling Zhao, Kang Zhang, Michael L Klein, Gregory S Hageman, G Mark Lathrop, Kari Stefansson, Rando Allikmets, Paul N Baird, Michael B Gorin, Jie Jin Wang, Caroline C W Klaver, Johanna M Seddon, Margaret A Pericak-Vance, Sudha K Iyengar, John R W Yates, Anand Swaroop, Bernhard H F Weber, Michiaki Kubo, Margaret M DeAngelis, Thierry Léveillard, Unnur Thorsteinsdottir, Jonathan L Haines, Lindsay A Farrer, Iris M Heid, Gonçalo R Abecasis, .
Nat. Genet.
PUBLISHED: 03-03-2013
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Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.
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Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 02-14-2013
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To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Womens Health Initiative Observational Study.
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Inclusion of genotype with fundus phenotype improves accuracy of predicting choroidal neovascularization and geographic atrophy.
Ophthalmology
PUBLISHED: 02-07-2013
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The accuracy of predicting conversion from early-stage age-related macular degeneration (AMD) to the advanced stages of choroidal neovascularization (CNV) or geographic atrophy (GA) was evaluated to determine whether inclusion of clinically relevant genetic markers improved accuracy beyond prediction using phenotypic risk factors alone.
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Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration.
Hum. Genomics
PUBLISHED: 12-14-2011
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Vitamin D has been shown to have anti-angiogenic properties and to play a protective role in several types of cancer, including breast, prostate and cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective for risk of a number of conditions, including cardiovascular disease and chronic kidney disease, as well as numerous autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study performed by Parekh et al. was the first to suggest a role for vitamin D in age-related macular degeneration (AMD) and showed a correlation between reduced serum vitamin D levels and risk for early AMD. Based on this study and the protective role of vitamin D in diseases with similar pathophysiology to AMD, we examined the role of vitamin D in a family-based cohort of 481 sibling pairs. Using extremely phenotypically discordant sibling pairs, initially we evaluated the association of neovascular AMD and vitamin D/sunlight-related epidemiological factors. After controlling for established AMD risk factors, including polymorphisms of the genes encoding complement factor H (CFH) and age-related maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1), and smoking history, we found that ultraviolet irradiance was protective for the development of neovascular AMD (p = 0.001). Although evaluation of serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) was higher in unaffected individuals than in their affected siblings, this finding did not reach statistical significance. Based on the relationship between ultraviolet irradiance and vitamin D production, we employed a candidate gene approach for evaluating common variation in key vitamin D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family 24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1) in this same family-based cohort. Initial findings were then validated and replicated in the extended family cohort, an unrelated case-control cohort from central Greece and a prospective nested case-control population from the Nurses Health Study and Health Professionals Follow-Up Studies, which included patients with all subtypes of AMD for a total of 2,528 individuals. Single point variants in CYP24A1 (the gene encoding the catabolising enzyme of the vitamin D pathway) were demonstrated to influence AMD risk after controlling for smoking history, sex and age in all populations, both separately and, more importantly, in a meta-analysis. This is the first report demonstrating a genetic association between vitamin D metabolism and AMD risk. These findings were also supplemented with expression data from human donor eyes and human retinal cell lines. These data not only extend previous biological studies in the AMD field, but further emphasise common antecedents between several disorders with an inflammatory/immunogenic component such as cardiovascular disease, cancer and AMD.
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Pilot application of iTRAQ to the retinal disease Macular Telangiectasia.
J. Proteome Res.
PUBLISHED: 12-14-2011
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We used the comparative proteomic technique iTRAQ coupled with offline 2DLC-MS/MS to analyze a rare specimen of the poorly understood, potentially blinding ophthalmic condition Macular Telangiectasia type 2 (MacTel type 2). We refined the technique using an internal standard consisting of pooled samples for each iTRAQ experiment to allow for multiple comparisons between different regions of the retina and different tissue donors. A total of 594 nonredundant proteins were identified in the retina and 168 in the vitreous, of which approximately half were found in significantly different abundance in the various comparisons made. The most prominent differences were found within the glycolytic pathway, where 8 proteins were reduced in the diseased macula compared with peripheral retina of the same eye, and 10 were also reduced in comparison with the macula of a control eye. Furthermore, Müller cell-associated proteins, including GFAP, VIME, and GLNA, were also reduced in the diseased macula, consistent with a link between the glycolytic pathway and Müller cells. These changes were validated by Western blotting and immunohistochemical studies. Proteomic analysis of the vitreous revealed an increase of proteins that were reduced in the retina. This supports proteomic analysis of the more easily available vitreous, which may reveal retina-specific protein changes associated with disease. Furthermore, our study has highlighted changes in the glycolytic pathway as a possible component of MacTel type 2 pathobiology.
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Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration.
Hum. Genomics
PUBLISHED: 08-03-2011
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Predictive tests for estimating the risk of developing late-stage neovascular age-related macular degeneration (AMD) are subject to unique challenges. AMD prevalence increases with age, clinical phenotypes are heterogeneous and control collections are prone to high false-negative rates, as many control subjects are likely to develop disease with advancing age. Risk prediction tests have been presented previously, using up to ten genetic markers and a range of self-reported non-genetic variables such as body mass index (BMI) and smoking history. In order to maximise the accuracy of prediction for mainstream genetic testing, we sought to derive a test comparable in performance to earlier testing models but based purely on genetic markers, which are static through life and not subject to misreporting. We report a multicentre assessment of a larger panel of single nucleotide polymorphisms (SNPs) than previously analysed, to improve further the classification performance of a predictive test to estimate the risk of developing choroidal neovascular (CNV) disease. We developed a predictive model based solely on genetic markers and avoided inclusion of self-reported variables (eg smoking history) or non-static factors (BMI, education status) that might otherwise introduce inaccuracies in calculating individual risk estimates. We describe the performance of a test panel comprising 13 SNPs genotyped across a consolidated collection of four patient cohorts obtained from academic centres deemed appropriate for pooling. We report on predictive effect sizes and their classification performance. By incorporating multiple cohorts of homogeneous ethnic origin, we obtained >80 per cent power to detect differences in genetic variants observed between cases and controls. We focused our study on CNV, a subtype of advanced AMD associated with a severe and potentially treatable form of the disease. Lastly, we followed a two-stage strategy involving both test model development and test model validation to present estimates of classification performance anticipated in the larger clinical setting. The model contained nine SNPs tagging variants in the regulators of complement activation (RCA) locus spanning the complement factor H (CFH), complement factor H-related 4 (CFHR4), complement factor H-related 5 (CFHR5) and coagulation factor XIII B subunit (F13B) genes; the four remaining SNPs targeted polymorphisms in the complement component 2 (C2), complement factor B (CFB), complement component 3 (C3) and age-related maculopathy susceptibility protein 2 (ARMS2) genes. The pooled sample size (1,132 CNV cases, 822 controls) allowed for both model development and model validation to confirm the accuracy of risk prediction. At the validation stage, our test model yielded 82 per cent sensitivity and 63 per cent specificity, comparable with metrics reported with earlier testing models that included environmental risk factors. Our test had an area under the curve of 0.80, reflecting a modest improvement compared with tests reported with fewer SNPs.
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Influence of ROBO1 and RORA on risk of age-related macular degeneration reveals genetically distinct phenotypes in disease pathophysiology.
PLoS ONE
PUBLISHED: 06-23-2011
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ROBO1 is a strong candidate gene for age-related macular degeneration (AMD) based upon its location under a linkage peak on chromosome 3p12, its expression pattern, and its purported function in a pathway that includes RORA, a gene previously associated with risk for neovascular AMD. Previously, we observed that expression of ROBO1 and RORA is down-regulated among wet AMD cases, as compared to their unaffected siblings. Thus, we hypothesized that contribution of association signals in ROBO1, and interaction between these two genes may be important for both wet and dry AMD. We evaluated association of 19 single nucleotide polymorphisms (SNPs) in ROBO1 with wet and dry stages of AMD in a sibling cohort and a Greek case-control cohort containing 491 wet AMD cases, 174 dry AMD cases and 411 controls. Association signals and interaction results were replicated in an independent prospective cohort (1070 controls, 164 wet AMD cases, 293 dry AMD cases). The most significantly associated ROBO1 SNPs were rs1387665 under an additive model (meta P = 0.028) for wet AMD and rs9309833 under a recessive model (meta P = 6 × 10(-4)) for dry AMD. Further analyses revealed interaction between ROBO1 rs9309833 and RORA rs8034864 for both wet and dry AMD (interaction P<0.05). These studies were further supported by whole transcriptome expression profile studies from 66 human donor eyes and chromatin immunoprecipitation assays from mouse retinas. These findings suggest that distinct ROBO1 variants may influence the risk of wet and dry AMD, and the effects of ROBO1 on AMD risk may be modulated by RORA variants.
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Basement membrane changes in capillaries of the ageing human retina.
Br J Ophthalmol
PUBLISHED: 05-23-2011
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The ultrastructural appearance of retinal capillaries can yield important information about disease mechanisms, but is not well characterised in human post mortem samples. We therefore aimed to create a baseline for the appearance of capillaries and establish how this is influenced by post mortem fixation delays and donor age.
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Vitamin D status and early age-related macular degeneration in postmenopausal women.
Arch. Ophthalmol.
PUBLISHED: 04-13-2011
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The relationship between serum 25-hydroxyvitamin D (25[OH]D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated in participants of the Carotenoids in Age-Related Eye Disease Study.
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Fundus autofluorescence and spectral-domain optical coherence tomography characteristics in a rapidly progressing form of geographic atrophy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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To further characterize a previously described phenotypic variant of geographic atrophy (GA) associated with rapid progression and a diffuse-trickling appearance on fundus autofluorescence (FAF).
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Variants in the APOE gene are associated with improved outcome after anti-VEGF treatment for neovascular AMD.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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Anti-vascular endothelial growth factor (anti-VEGF) drugs have dramatically improved the treatment of neovascular AMD. In pivotal studies, almost 90% of patients maintain vision, with approximately 30% showing significant improvement. Despite these successes, 10% to 15% of patients continue to lose vision, even with treatment. It has been reported that variants in some AMD-associated genes influence treatment outcome. This study showed an association of treatment outcome with variants in the apolipoprotein E (APOE) gene.
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Serum VEGF and CFH in exudative age-related macular degeneration.
Curr. Eye Res.
PUBLISHED: 12-15-2010
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To determine serum vascular endothelial growth factor 165 (VEGF165) levels and the association of the complement factor H gene (CFH) Y402H polymorphism in patients with exudative age-related macular degeneration (AMD) in comparison to unaffected control subjects.
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Heparan sulfate, including that in Bruchs membrane, inhibits the complement alternative pathway: implications for age-related macular degeneration.
J. Immunol.
PUBLISHED: 09-27-2010
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An imbalance between activation and inhibition of the complement system has been implicated in the etiologies of numerous common diseases. Allotypic variants of a key complement fluid-phase regulatory protein, complement factor H (CFH), are strongly associated with age-related macular degeneration (AMD), a leading cause of worldwide visual dysfunction, although its specific role in AMD pathogenesis is still not clear. CFH was isolated from individuals carrying combinations of two of the nonsynonymous coding variants most strongly associated with AMD risk, V62/H402 (risk haplotype variants), I62/Y402 (nonrisk haplotype variants), and V62/Y402. These proteins were used in two functional assays (cell surface- and fluid-phase-based) measuring cofactor activity of CFH in the factor I-mediated cleavage of C3b. Although no variant-specific differences in the cofactor activity were detected, when heparan sulfate (HS) was added to these assays, it accelerated the rate of C3b cleavage, and this effect could be modulated by degree of HS sulfation. Bruchs membrane/choroid, a site of tissue damage in AMD, contains high concentrations of glycosaminoglycans, including HS. Addition of human Bruchs membrane/choroid to the fluid-phase assay accelerated the C3b cleavage, and this effect was lost posttreatment of the tissue with heparinase III. Binding of CFH variants to Bruchs membrane/choroid isolated from elderly, non-AMD donor eyes, was similar, as was the functional activity of bound CFH. These findings refine our understanding of interactions of HS and complement and support the hypothesis that these interactions play a role in the transition between normal aging and AMD in Bruchs membrane/choroid.
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Vitreoschisis in macular diseases.
Br J Ophthalmol
PUBLISHED: 06-28-2010
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Vitreoschisis is a possible pathogenic mechanism in macular diseases. Thus, the vitreoretinal interface was evaluated in monkey eyes and patients with various macular diseases in search of vitreoschisis. It is hypothesised that vitreoschisis is present in macular holes (MH) and macular pucker (MP), but not in other maculopathies.
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Complement, age-related macular degeneration and a vision of the future.
Arch. Ophthalmol.
PUBLISHED: 03-10-2010
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Age-related macular degeneration (AMD) is one of the most well-characterized late-onset, complex trait diseases. Remarkable advances in our understanding of the genetic and biological foundations of this disease were derived from a recent convergence of scientific and clinical data. Importantly, the more recent identification of AMD-associated variations in a number of complement pathway genes has provided strong support for earlier, paradigm-shifting studies that suggested that aberrant function of the complement system plays a key role in disease etiology. Collectively, this wealth of information has provided an impetus for the development of powerful tools to accurately diagnose disease risk and progression and complement-based therapeutics that will ultimately delay or prevent AMD. Indeed, we are poised to witness a new era of a personalized approach toward the assessment, management, and treatment of this debilitating, chronic disease.
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Perifoveal müller cell depletion in a case of macular telangiectasia type 2.
Ophthalmology
PUBLISHED: 03-09-2010
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To assess the histopathologic changes in a postmortem sample derived from an eye donor with macular telangiectasia (MacTel) type 2 to gain further insight into the cause of the disease.
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The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited.
Prog Retin Eye Res
PUBLISHED: 12-02-2009
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During the past ten years, dramatic advances have been made in unraveling the biological bases of age-related macular degeneration (AMD), the most common cause of irreversible blindness in western populations. In that timeframe, two distinct lines of evidence emerged which implicated chronic local inflammation and activation of the complement cascade in AMD pathogenesis. First, a number of complement system proteins, complement activators, and complement regulatory proteins were identified as molecular constituents of drusen, the hallmark extracellular deposits associated with early AMD. Subsequently, genetic studies revealed highly significant statistical associations between AMD and variants of several complement pathway-associated genes including: Complement factor H (CFH), complement factor H-related 1 and 3 (CFHR1 and CFHR3), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3). In this article, we revisit our original hypothesis that chronic local inflammatory and immune-mediated events at the level of Bruchs membrane play critical roles in drusen biogenesis and, by extension, in the pathobiology of AMD. Secondly, we report the results of a new screening for additional AMD-associated polymorphisms in a battery of 63 complement-related genes. Third, we identify and characterize the local complement system in the RPE-choroid complex - thus adding a new dimension of biological complexity to the role of the complement system in ocular aging and AMD. Finally, we evaluate the most salient, recent evidence that bears directly on the role of complement in AMD pathogenesis and progression. Collectively, these recent findings strongly re-affirm the importance of the complement system in AMD. They lay the groundwork for further studies that may lead to the identification of a transcriptional disease signature of AMD, and hasten the development of new therapeutic approaches that will restore the complement-modulating activity that appears to be compromised in genetically susceptible individuals.
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New era for personalized medicine: the diagnosis and management of age-related macular degeneration.
Clin. Experiment. Ophthalmol.
PUBLISHED: 11-03-2009
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It can be argued that age-related macular degeneration is one of the best characterized complex trait diseases. Extensive information related to genetic and environmental risk factors exists, and a number of different biological pathways are strongly implicated in its aetiology. Along with recent improvements in high throughput and relatively inexpensive genetic technologies, we are now in a position to consider developing a presymptomatic, personalized approach towards the assessment, management and treatment of this disease. We explore the applicability and challenges of this approach if it is to become commonplace for guiding treatment decisions for individuals with pre-existing disease or for those at high risk of developing it.
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Retinal basement membrane abnormalities and the retinopathy of Alport syndrome.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-22-2009
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To determine the effects of X-linked and autosomal recessive Alport syndrome on retinal basement membranes and how these result in the characteristic perimacular dot-and-fleck retinopathy, lozenge, and macular hole.
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Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: a systems biology based approach.
Vision Res.
PUBLISHED: 06-17-2009
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To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology.
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Rapid and sensitive method for detection of Y402, H402, I62, and V62 variants of complement factor H in human plasma samples using mass spectrometry.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 04-11-2009
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Variations in the complement factor H (CFH) gene are tightly associated with age-related macular degeneration (AMD) across diverse populations. Of the many nonsynonymous coding variants in CFH, two are most strongly associated with increased risk of AMD: isoleucine 62 to valine (I62V) and tyrosine 402 to histidine (Y402H). Detection of these variations in a patients blood is important for a risk assessment of AMD and disease prognosis. However, traditional methods of genetic analysis cannot be used for measuring CFH allotypes in some sources of human plasma and other biological fluids not containing DNA. The purpose was to develop a protein-based method of detecting CFH allotypes.
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Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia.
Br J Ophthalmol
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To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2.
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Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration.
Mol. Vis.
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Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress-mediated AMD pathology.
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Delay to treatment and visual outcomes in patients treated with anti-vascular endothelial growth factor for age-related macular degeneration.
Am. J. Ophthalmol.
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To investigate the potential influences that affect visual acuity (VA) outcome in a clinic-based cohort of age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) treatment for choroidal neovascularization.
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Prospective Study of Common Variants in CX3CR1 and Risk of Macular Degeneration: Pooled Analysis From 5 Long-term Studies.
JAMA Ophthalmol
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IMPORTANCE The CX3CR1 gene is implicated as a candidate gene for age-related macular degeneration (AMD) through several lines of evidence. There is uncertainty, however, as to whether common genetic variants in CX3CR1 alter risk of AMD, since prior studies have been inconsistent and mostly limited to evaluation of 2 nonsynonymous variants, T280M (rs3732378) and V249I (rs3732379). OBJECTIVE To determine if common variants in CX3CR1 predict future risk of AMD. DESIGN, SETTING, AND PARTICIPANTS Prospective nested case-control study within 5 large study populations with long-term follow-up. We measured genotypes for T280M, V249I, and 13 other common single-nucleotide polymorphisms (SNPs) of the CX3CR1 gene among people who developed AMD (n?=?1110, including 369 with neovascular AMD) and 2532 age- and sex-matched controls. MAIN OUTCOMES AND MEASURES We determined the incidence rate ratios (RR) and 95% CIs for incidence of AMD for each variant and examined interactions with other AMD-associated variants and modifiable risk factors. RESULTS In additive genetic models, we identified nonsignificant associations with AMD for T280M (RR, 0.87; P?=?.07) and 3 other SNPs, rs2853707 (RR, 0.88; P?=?.07), rs12636547 (RR, 0.85; P?=?.10), and rs1877563 (RR, 0.84; P?=?.06), 1 of which, rs2853707, is positioned in the CX3CR1 promoter region and was associated with neovascular AMD (RR, 0.75; P?=?.03). We observed that a recessive model was a better fit to the data for some SNPs, with associations between rs11715522 and AMD (RR, 1.27; P?=?.03) and between rs2669845 (RR, 3.10; P?=?.04), rs2853707 (RR, 0.48; P?=?.050), and rs9868689 (RR, 0.31; P?=?.02) and neovascular AMD. Moreover, in exploratory analyses, we identified a number of possible interactions including between V249I and rs2669845 and dietary intake of ?-3 fatty acids (P?=?.004 and P?=?.009, respectively) for AMD; between rs2669845 and obesity (P?=?.03) for neovascular AMD; between T280M and complement component 3 (C3) R102G for AMD (P?=?.03); between rs2669845 and Y402H in complement factor H for AMD (P?=?.04); and between rs2669845, rs2853707, and V249I and C3 R102G for neovascular AMD (P?=?.008; .04; and .002, respectively). CONCLUSIONS AND RELEVANCE This study failed to identify significant associations between common CX3CR1 variants and AMD after considering the number of SNPs analyzed and multiple comparisons. However, we observed evidence consistent with recessive modes of association and that an effect of CX3CR1 variants may depend on other factors including dietary intake of ?-3 fatty acids, obesity, and genotypes at CFH Y402H and C3 R102G. If replicated in other populations, these findings would support a role for CX3CR1 in AMD but also suggest that its role may involve mechanisms that are independent of the T280M/V249I variations.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.