UCLA

Diseases that cause photoreceptor degeneration such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP) affect millions of people and lead to blindness. The degeneration of photoreceptor cells in AMD or cone photoreceptors in RP is caused by stress in their environment and/or lack of trophic support, not by direct genetic mutation targeting of the photoreceptor cells. Therefore, providing effective trophic support can delay or prevent photoreceptor degeneration. It has been known for more than 20 years that natural trophic factors exist in the retina that protect photoreceptor cells, but these factors have never been identified. Recent gene therapy studies have revealed that targeting genetic mutations is not sufficient and that there is an urgent need to identify trophic factors that can maintain photoreceptor survival in the treatment of photoreceptor degeneration. Identification and mechanistic study of trophic factors naturally present in the retina will lead to a better understanding of the photoreceptor protection mechanism and help to develop new therapeutic strategies. My thesis project aims to identify new natural trophic factors that protect photoreceptor cells and to test them using in vitro and in vivo models.

We found that natural trophic factors in the retina strongly protect photoreceptor cells from retinal-mediated light damage or chemically induced oxidative damage. Using classic techniques combined with advanced mass spectrometry and genome-wide database searching, we identified several candidate photoreceptor protective factors. These factors effectively protect primary cone photoreceptor cells from light damage and oxidative damage in vitro. We cloned candidate genes into lentiviral vectors and delivered them to the retina and RPE (retinal pigment epithelium) in vivo by subretinal injection. Using two mouse models of retinal degeneration: a light-induced retina degeneration model and a genetic retina degeneration model, we found that one factor almost completely protect retina from light-induced damage in vivo. In summary, we have identified a novel factor that can prevent photoreceptor cell degeneration in vitro and in vivo. This factor has potential therapeutic values in treating retina degenerative diseases.