Photoreceptor cells are a highly specialized cell type in the eye. They capture light and transform the light signals into chemical signals that are delivered to other types of neurons in the eye. Vision is thus initiated by photoreceptors and relies completely upon proper photoreceptor survival. In many inherited diseases that lead to blindness, the disease gene directly affects photoreceptor cells. One such disease, retinitis pigmentosa (RP), has disease genes that directly affect rods, the photoreceptor type that mediates vision in dim light. People born with RP are thus night blind. Subsequent to rod dysfunction and death, the cone photoreceptors, which mediate color and daylight vision, also lose function and die. We have suggested a model wherein cones are affected due to dysregulated metabolism, which occurs after rods die. Cones do not express most RP disease genes, but they do experience a greatly altered environment following rod death. The outer segments of the cone collapse lose their intimate association with their support cells and are exposed to a hyperoxic environment. We have begun to develop gene therapy to combat some of these problems. Our approach is to use adenovirus-associated vectors (AAV) to deliver genes that help cones fight oxidation and other forms of stress. Our progress in treating RP mice using such vectors will be presented.
Dr. Cepko is the Bullard Professor of Genetics and Neuroscience at Harvard Medical School and an Investigator of the Howard Hughes Medical Institute. She received her Ph.D. degree from the Massachusetts Institute of Technology, working with Phillip Sharp, and remained at MIT as a postdoctoral fellow in the laboratory of Richard Mulligan, where she helped develop the technology of retrovirus-mediated gene transduction. Her current research is focused on the development of the central nervous system, with an emphasis on the retina. Her laboratory has also been working to develop gene therapy for prolonging vision in genetic forms of blindness, and in developing viral vectors for tracing neuronal circuitry. She is a member of the National Academy of Sciences and the American Academy of Arts and Sciences.