Interindividual Variation in Retinal Pigmented Epithelium Energy Metabolism and Regulation of the Process

The nerves that sense light in the eye and the cells of the retinal pigment epithelium (RPE) form a critical partnership necessary for vision. Through our proposed research, we seek to understand how the capability of RPE cells to get energy from food molecules varies among human individuals due to differences in their genes and how RPE cells control this process. RPE cells are involved in the development and progression of the most common types of macular degeneration, including age-related macular degeneration (AMD). Successful completion of this project may help us to better understand why macular degeneration affects some people more than others, eventually leading to improved treatment for this disease.

RPE cells are thought to be the site of the initial damaging events that lead to nerve cell death in age-related macular degeneration (AMD). Evidence suggests that RPE cells may lose the ability to generate energy and that may be an important reason that nerve cells die in the disease. We are investigating how the capability of RPE cells to obtain energy from food molecules varies among humans due to genetic differences. We are carrying out a set of standardized tests of cellular energy metabolism on a panel of RPE cell lines, each of which has a unique genetic makeup. We are searching for specific genetic differences that explain the differences in RPE cell function that our tests detect. Our work is innovative because of our focus on RPE cellular energy metabolism and because we are studying the effects of common genetic differences directly on RPE cells. The success of this project will help us to better understand why AMD affects some people more than others, perhaps leading to personalized treatment for this disease.