Yale Team Identifies Macular Degeneration Gene

On the very day that Yale was celebrating the completion of the macular degeneration research campaign, an announcement went out world-wide that scientists at Yale had identified a gene for age-related macular degeneration (ARMD). The paper describing this work was published in the March 10, 2005 issue of the journal Science. Dr. Colin Barnstable, Vice-Chair of Research in the Department of Ophthalmology and Visual Science and Director of the Macular Degeneration Research Center, joined team leader Dr. Josephine Hoh, of the Department of Epidemiology and Public Health, and Dr. Caroline Zeiss, of the Department of Comparative Medicine, along with scientists at Rockefeller University and the National Eye Institute, in pinpointing a gene that increases the risk of ARMD by more than sevenfold.

The gene is located on chromosome 1 and codes for Complement Factor H (CFH). Since announcing this finding to the scientifc community, the role of CFH in ARMD has been confirmed by at least four other groups. "This is the first study to identify a common variant of the specific gene associated with ARMD," said Dr. Hoh, although she cautioned that "We can't say that this is the single gene for ARMD. This is one of the genes that contributes." Dr. Barnstable noted that "This is a very important advance. We found a molecule that plays a substantial role in many cases of ARMD."

Having discovered a gene for a disease is only the beginning of a long process in understanding what the gene does, how it is involved in the disease and what treatment can prevent it's effect. Already, however, the identification of CFH in ARMD has given insight into the mechanism of macular degeneration. Since the protein limits the inflammatory response, it lends support to the idea that there is an inflammatory component in the cause of ARMD. "Drugs regulating the inflammatory process may be of value in controlling this disease," stated Dr. Barnstable.

Dr. Barnstable, in collaboration with Dr. Joyce Tombran-Tink of the University of Missouri and a visiting Associate Professor in our department, has made yet another potentially important discovery with regard to the wet form of ARMD. In this, the most severe form of the disease, abnormal blood vessels grow beneath the macular portion of the retina, where they leak and bleed. Growth of these vessels is stimulated by the molecule Vascular Endothelial Growth Factor (VEGF), and preventing that growth is critical in the management of ARMD. Drs. Barnstable and Tombran-Tink have shown that the molecule Pigment Epithelial Derived Factor (PEDF) inhibits VEGF and they have identified the molecular target that PEDF interacts with to stop VEGF from signaling growth of vessels.

Early clinical trials are underway to evaluate PEDF as a therapy for wet ARMD. "This work will provide new ways of measuring the effectiveness of treatment and of designing new generations of drugs that work in the same way," noted Dr. Barnstable.