Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Degeneration of the light-sensitive cells within the eye (photoreceptors) results in irreversible vision loss, and inherited photoreceptor degenerations affect ~1/3000 individuals. Typically, degenerations impact either cone photoreceptors (responsible for daytime/colour vision) or rod photoreceptors (responsible for dim-light vision). Specific mutations in the gene Retinitis Pigmentosa 1-Like 1 (RP1L1) have been found to cause a rare cone degeneration, Occult Macular Dystrophy (OMD). Conversely, loss of RP1L1 leads to a rod degeneration, retinitis pigmentosa (RP); RP is the most common photoreceptor degeneration. The underlying disease mechanisms causing photoreceptor death when RP1L1 is mutated or lost are not known, which makes intervention to prevent vision loss challenging. How and why disease can lead to death of one photoreceptor type and not the other is unclear, which makes the development of photoreceptor type-specific therapies difficult. This work will provide unique insights into the fundamental differences between rods and cones and how this impacts disease. Zebrafish are an ideal model for studying photoreceptors, as they have a diversity of cones similar to that of the human retina and many tools available for photoreceptor study. Zebrafish models of RP and OMD will allow for characterization of disease progression, including early disease indicators, and elucidation of disease mechanism(s). This project will explore what RP1L1 is doing in healthy rods versus cones, how this changes in disease models, and what makes rods and cones distinct. Appreciating disease mechanism, as well as the molecular distinctions between rods and cones that make them differentially susceptible to disease, will allow for targeted intervention. Information about the fundamental differences between rods and cones and how this impacts disease can be applied to a broad range of photoreceptor diseases, allowing for development of new therapeutics.