A Genetic Model of RPE Dysfunction in ARMD

This project will analyze the effects of vacuolar ATPase mutations in zebrafish, an animal model system in which human diseases can be studied. Zebrafish vacuolar ATPase mutants show severe AMD-like pathologies in their eyes and are, therefore, an excellent animal model system in which AMD progression can be further understood.

Grantee institution at the time of this grant: The University of Texas at Austin

In patients with the dry form of age-related macular degeneration (ARMD), a substance called drusen builds up in cells of the retinal pigment epithelium (RPE) – the pigmented layer at the back of the eye. Drusen poisons RPE cells by inhibiting their ability to degrade protein and lipid components of photoreceptors – the light-sensitive cells of the retina. Normally, RPE cells help to maintain the survival of photoreceptors by continually removing their tips, which have accumulated cellular damage over time. Dr. Gross will study the mechanisms that RPE cells utilize to facilitate photoreceptor degradation, focusing on a protein complex called the vacuolar ATPase that is necessary for degradative processes in other cell types. Dr. Gross predicts that mutations in the vacuolar ATPase complex lead to ARMD in humans.