The overall goal of this laboratory is to determine the molecular factors involved in age-related macular degeneration (AMD), a leading cause of blindness in the US. The pathophysiology of AMD is complex involving the natural aging process, genetics and environmental factors. Presently we are concentrating our efforts on studying the effects of oxydized cholesterol and the oxysterol binding proteins (OSBPs) in the retina and pigment epithelium. Oxydized forms of cholesterol are known to have potent toxic pharmacological effects that can inhibit cholesterol synthesis and induce apoptosis in cells. We are investigating the possibility that the accumulation of these oxysterols in the retina (drusen deposits) may be contributing to the pathology of AMD by poisoning the pigment epithelium. The OSBPs are a family of proteins that share similar structural domains. We have isolated a member of this family that is expressed almost exclusively in the retina and pigment epithelium. We are also pursuing other approaches to studying AMD. We are screening 1100 AMD patients and age-matched controls for mutations in known retinal genes in an attempt to find a genetic correlation to the disease. This could help determine which biochemical pathways are failing and to formulate strategies for treatment and/or prevention. We are also continuing to search for novel genes expressed in the retina and macula. - macula retina macular degeneration pigment epithelium degeneration genes
