Drug Screening to Modulate RPE Lysosomal Dynamics in AMD

Age-related macular degeneration (AMD) is a disease that stems from a variety of factors and exhibits several different features. This makes it difficult to gain insight into the disease process that is essential for designing drug therapies. It is now believed that the primary insult in AMD occurs in cells of the retinal pigment epithelium (RPE) that underlie the photoreceptors or the light-sensing cells of the retina. While researchers have shown that a by-product of the visual cycle known as “A2E” may damage the RPE, a complete understanding of how this occurs is still lacking. It is known that A2E accumulates in organelles called lysosomes, which are the degradative compartments of the cell. Our laboratory work has shown that A2E interferes with lipid metabolism in the RPE. The research proposed in this application aims to use a powerful technique called high-throughput screening to examine the potential of 20,000 chemical compounds to either remove A2E from the cell or restore normal lipid metabolism in the RPE. We hope that our research will not only identify potential drug candidates but also open new lines of inquiry into understanding how vision loss occurs in AMD.