A Genetic Model of RPE Dysfunction in ARMD

Project Summary

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. To test this prediction, Dr. Gross 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 ARMD-like pathologies in their eyes and are therefore an excellent animal model system in which ARMD progression can be further understood.