Grant: Project Grant

Inherited retinal degenerative diseases are a heterogeneous group of disorders that are a major cause of blindness in Canada and the developed world. They are typically characterized by progressive loss in vision resulting from mutations in genes encoding proteins essential for the survival of rod and cone photoreceptor cells. Stargardt macular degeneration (STGD1) linked to mutations in the membrane transporter ABCA4 is the most common monogenic inherited retinal degenerative disease. Affected individuals typically experience loss in central vision in their first decade of life often progressing to total blindness in later years. Mutations in ABCA4 are also associated with other severe retinal diseases including retinitis pigmentosa and age-related macular degeneration. My lab has shown that ABCA4 functions in the removal of vitamin A derivatives known as retinoids that are produced as part of the visual process. Disease-associated mutations cause a loss in the ability of ABCA4 to remove retinoids. As a result toxic retinoid compounds accumulate causing photoreceptor cell death and a loss in vision. The goal of this research is to further understand the molecular structure and function of ABCA4 and determine how mutations in this protein cause a loss in vision. This information together with our expertise in retinal degenerative diseases will be used to design and develop novel pharmaceutical agents (drugs) as promising treatments for STGD1. This research will increase our knowledge of the visual system and retinal degenerative diseases and lead to therapeutic treatments that will improve the health care and quality of life of individuals with STGD1 and related diseases, and reduce their economic burden on society. Our research program will also train graduate students and postdocs for future careers in basic science and translational medicine and produce new intellectual property and commercialization that will benefit Canada.