Congenital Disorders, Genetics and Epigenetics

Dr. Debra Thompson studies the molecular basis of inherited forms of retinal degeneration, a constellation of diseases resulting in the death of the rod and cone photoreceptors, the light-sensing cells of the retina.  The long-term goal of her studies is to contribute to the development targeted therapies for these diseases.

Inherited retinal degeneration is caused by mutations in the genes necessary for critical aspects of the physiology of the rods and cones, as well as the retinal pigment epithelium (RPE) that supports their function.  Leber congenital amaurosis (LCA) is a particularly severe form of inherited retinal degeneration resulting in blindness in the first or second decade of life.  Dr. Thompson’s studies led to the identification of three LCA genes – RPE65, LRAT, and RDH12 – that impact vitamin A metabolism necessary for the synthesis and recycling 11-cis retinal that is used a chromophore by the rods and cones to absorb light.  Current efforts focus on defining the factors that regulate the efficiency of the vitamin A cycle, as well as the links between defects in this pathway and the resulting death of the rod and cones.  Another aspect of her research focuses on the phagocytic activity of the retinal pigment epithelium that is essential for the mechanism of photoreceptor cell renewal needed to maintain rod and cone function.  Current studies involve characterization of the signaling mechanism downstream of the phagocytosis receptor MERTK whose gene is mutated in some cases of retinitis pigmentosa.

Dr. Thompson is involved internationally in collaborative studies of small molecule and gene-therapy approaches for treating inherited retinal degeneration.  The ultimate goal of the work is to identify strategies for improving outcomes in individuals with retinal degeneration that can rescue both early- and late-onset forms of these blinding diseases.