Understanding the Huge Impact of Single Base Variation on Gene in AMD
Recently, genome-wide association studies (GWAS) have identified four DNA variants that are strong age-related macular degeneration (AMD) risk factors. The ARMS2 and HTRA1 loci confer the most significant genetic risk in the history of human GWAS studies. However, until now, the physical genomic proximity of these two loci has frustrated efforts to study their independent contributions to AMD pathogenesis. In the research proposed here, we plan to circumvent these obstacles through the application of gene editing invalidated, patient-specific stem cells. Given that these rapidly proliferating cells more closely resemble embryonic cells than aged adult cells, they likely do not provide the appropriate environment to study the molecular biology of aging. We propose to use cells that have been pharmacologically aged, enabling our model to better recapitulate the conditions present in the older adult eye and ultimately identify appropriate areas of intervention. Using this innovative approach, we will develop a patient-specific disease model to test the particular mutations addressed in this application.