OA1 Signaling and AMD

The studies proposed in this application investigate a molecular pathway in the retinal pigmented epithelium, RPE, that governs neurotrophic factor production. Activation of OA1 signaling is a valid and potentially import target for age-related macular degeneration (AMD) treatment. Data that support the hypothesis of this proposal will have the effect of illustrating a new and important treatment route for AMD.

RPE cells function to maintain the health of the retina throughout life, and failure in this important function is likely to be a part of age-related macular degeneration (AMD) pathology. How to control RPE support of the retina is an important goal for this laboratory because if we could find a way to increase this RPE function, we may be better able to treat or prevent AMD. We have identified a novel pathway likely to play an important role in controlling this RPE function. In this study, we will test whether up or down-regulation of this pathway protects the retina from damage. Our studies will identify the pathway and mechanism responsible for retinal survival. Once completed, this information can be used to develop drugs that could slow or prevent AMD. To accomplish this we are using several transgenic mice lineages with defects in specific genes. Using these mice, we are testing whether we can overcome this deficit using the novel pathway we have identified. Finally, we are using mice with a deletion of a specific gene that likely contributes to retinal protection to determine if this is how the RPE protects the retina. The novel pathway we have discovered has never been investigated in this manner, largely because we have only recently identified how to regulate the pathway and how it contributes to retinal health and survival.