Debra A. Thompson, Ph.D.
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 photoreceptor cells. Inherited retinal degeneration is caused by mutations in genes encoding proteins involved in critical aspects of the physiology of the photoreceptor cells, as well as the retinal pigment epithelium (RPE) that supports photoreceptor cell function. Her studies include analysis of the basic functions of the proteins encoded by retinal dystrophy genes, as well as the pathogenetic mechanisms resulting from genetic mutations. Her long-term goal is to contribute to the foundation needed to develop targeted therapies for inherited retinal degeneration.
One aspect of Dr. Thompson's research focuses on disease genes responsible for Leber congenital amaurosis (LCA), a childhood-onset form of severe visual handicap resulting in blindness in the first or second decade of life. Her studies led to the identification of three LCA genes – RPE65, LRAT, and RDH12 – that impact vitamin A metabolism involved in the synthesis and recycling of the visual pigment chromophore, 11-cis retinal. 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 rod and cone photoreceptor cells.
A related area of Dr. Thompson’s work focuses specifically on identifying of the molecular signals necessary for cone photoreceptor development and viability. The goal of these studies is to further understand the biology of the cone-rich central retina that is damaged in age-related macular degeneration, and to identify survival factors and pathways potentially relevant to the development of treatments.
Dr. Thompson is also part of a consortium focused on developing treatment strategies for X-linked retinal dystrophies. These are severe forms of retinal degeneration caused by mutations in genes on the X-chromosome. She studies the diseases resulting from mutations in the RPGR gene. The goal is to develop novel methods of small molecule intervention and reliable outcomes measures for treatment protocols.
Another aspect of Dr. Thompson’s research involves studying the phagocytic mechanism by which the RPE eliminates membranes shed from the photoreceptor outer segments as part of their continuous renewal. The MERTK gene encodes a receptor tyrosine kinase essential for RPE phagocytosis, which when mutated causes certain forms of retinitis pigmentosa. Her studies have identified novel MERTK mutations in patients and unusual patterns of inheritance of these mutations. They have provided functional analysis of the mutant MERTK protein. Current efforts are focused on identifying MERTK downstream signaling partners necessary for phagocytic uptake and critical for photoreceptor cell survival.