Funding outcome

The retinal pigment epithelium is an essential layer of cells inside the eye involved in the maintenance of photoreceptors, the light-sensing elements of the retina. Peroxisomes and lysosomes are components of the cell that are critical in breaking down old photoreceptors, facilitating their turnover. These subcellular components interact and enable the movement of lipids such as cholesterol from lysosomes to peroxisomes. Children with disorders of peroxisome function develop retinal degeneration for which there is no treatment. This has massive implications on a child's life as they cannot see and perform tasks on their own. Our lab has shown that RPE cells that are missing peroxisome function cannot effectively break down photoreceptors. I hypothesize that this is caused by secondary dysfunction of lysosomes, the major digestive compartments of the cell. Our objective is to determine if cells lacking peroxisome function accumulate cholesterol in lysosomes, resulting in their dysfunction. To further support our hypothesis, I will assess if chemically lowering cholesterol in lysosomes can enhance lysosome function. If successful, this may inform the development of vision-saving treatments for children with disorder of peroxisome function. Methods used include culturing human-derived RPE cells, confocal immunofluorescence microscopy for localization of cholesterol in RPE cells, and western blotting for lysosome/RPE functionality analysis (phagocytosis assay). My project will enhance our understanding of how peroxisomes and lysosomes interact in RPE cells to regulate photoreceptor turnover.