Project description:We profiled using single cell RNA sequencing the peripheral blood mononuclear cells from control patients and patients with age-related macular degeneration (AMD).
Project description:Age-related macular degeneration (AMD) is a leading cause of vision loss, with its dry form characterized by retinal pigment epithelium (RPE) degeneration and photoreceptor loss. However, the underlying mechanisms driving these pathological changes remain poorly understood. Here, we identify a critical role for microglia-RPE cell interactions mediated by the SPP1-ITGAV signaling axis in dry AMD pathogenesis.
Project description:In age-related macular degeneration (AMD), both systemic and local zinc concentrations are decreased. Elevating zinc levels by nutrition or oral supplementation has a positive impact on delaying the progression to end-stage AMD in clinical studies. Here we set out to identify key regulatory pathways involved in this beneficial effect.
Project description:Multi-site, cross-sectional study, including subjects with Age-related Macular Degeneration (early, intermediate and late disease) and a control group of subjects without any macular diseases. Plasma metabolomic profiles were assessed using Nuclear Magnetic Resonance Spectroscopy (NMR). Multivariate statistics were performed to compare metabolomic profiles of AMD patients vs controls.
Project description:We report that decreased expression and activity of AhR exacerbates murine neovascular age-related macular degeneration, and increases cell migration and tube formation. The mechanism involves increased expression of pro-angiogenic mediators and altered matrix degradation. The results of our study suggest that the AhR signaling pathway may be important in multiple AMD related pathways. Gene expression analysis in the retinal pigment epithelium (RPE)-choroid tissue from AhR knockout mice contrasted against wild-type age-matched controls.
Project description:<p>Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. To further our understanding of AMD genetics, we examined the contribution of common and rare genetic variation in the International AMD Genomics Consortium that included ~50,000 samples of 26 AMD case - control cohorts that were jointly genotyped. Analyzing 16,144 patients with late stage AMD and 17,832 controls, we identified 52 independently associated common and rare variants distributed across 34 loci. Besides these single variant signals, we also observed gene-based enrichment of very rare coding variants (frequency < 0.1%) in cases that implicated causal roles for <i><a href="http://www.ncbi.nlm.nih.gov/gene/3075">CFH</a></i>, <i><a href="http://www.ncbi.nlm.nih.gov/gene/3426">CFI</a></i> and <i><a href="http://www.ncbi.nlm.nih.gov/gene/7078">TIMP3</a></i> in three of the known AMD risk loci. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.</p>
Project description:Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. In this study we investigated changes in differentated human retinal pigmented epithelial (RPE) cells to acute compared to chronic wounding. There are many interesting phenotypic and transcriptomic changes that occur after chronic wounding compared to acute wounding conditions which may have implications for AMD.
Project description:We performed a proteomic analysis of a retinal pigment epithelium cell line (ARPE-19) exposed to long-term sublethal levels of H2O2 to mimic low-level pro-oxidative insult in age-related macular degeneration (AMD). using a wide range of biochemical analyses and cell culture techniques, we highlighted changes in energy metabolism, extracellular matrix organization and inflammation-related processes, which may help in understanding the molecular pathogenesis of AMD.
