The gene responsible for age-related macular degeneration (AMD) – the leading cause of vision loss in the elderly – was recently identified by scientists at the BU School of Medicine , the University of Texas Southwestern Medical Center at Dallas , and Sequonom, Inc. Two additional studies published simultaneously – one by a team led by Margaret A. Pericak-Vance at Duke University Medical Center, and the other by Josephine Hoh at the Yale University School of Medicine found similar results.

The BU team, which includes Lindsay Farrer, professor and chief of the genetics program at the School of Medicine and Albert O. Edwards, president of the Institute for Retina Research at the Presbyterian Hospital of Dallas, searched through nearly 14 million base pairs on a region of chromosome one in an area that has long been suspected of harboring a gene responsible for the disease. They employed Sequonom’s MassARRAY technology, a highly-automated genetic amplification and analysis system that was developed by Charles Cantor, Sequonom’s chief scientific officer and director of BU’s Center for Advanced Biotechnology.

The researchers analyzed genetic material from two groups of test subjects – one comprised of people with early stage AMD, the other without the disease. They searched for single nucleotide polymorphisms, known as SNP’s –the genetic equivalent of a typo in a sentence – that were present in the chromosome of those with AMD and absent in those who were disease free.

They discovered a specific SNP located on chromosome one that interferes with production of a protein called Complement Factor H (CFH), a protein that is involved in controlling inflammation. According to the researchers, the presence of the genetic defect may increase a person’s chances of developing AMD by almost three-fold, and may be responsible for fifty percent of all cases of AMD.

According to the Macular Degeneration Foundation, a case of AMD is diagnosed every three minutes in the United States – one in six people between the ages of 55 and 64 in the U.S. has AMD; one in four between the ages of 64 and 74; and one in three over the age of 75. And, the number of people with the disease is likely to reach 3 million by 2020.

People with AMD experience deteriorating sight in the center of their field of view, vision that is essential to everyday activities such as reading and driving. The loss of vision results from damage to the macula, the central part of the retina that is rich in photosensitive cells. In affected individuals yellow deposits known as drusen, composed of inflammatory proteins, accumulate in the macula. The scientists speculate that the inflammatory reaction and destruction of healthy cells may, in individuals with the genetic variation, result from compromised production of CFH.

There are two forms of macular degeneration. The more common "dry" form progresses relatively slowly. The less common "wet" form, involving bleeding in the eye, can destroy vision rapidly. Both forms appear to be associated with the CFH gene variation.

According to Farrer, “Although environmental factors such as smoking and obesity also play a significant role in the development of AMD, we hope that our identification of the genetic anomaly associated with AMD will result in new and effective interventions for a significant number of people afflicted with the genetically linked form of this disease.”

The study appeared in the March 10, 2005 issue of the journal, Science.

— Joan Schwartz and Elana Hayasaka

Image: Example of how an individual with macular degeneration might see an image. Image courtesy of VisionCare.