Illness that blinds millions linked to genetic mutation

WASHINGTON -- The leading cause of blindness in the elderly, age-related macular degeneration, has been linked to a gene mutation, raising hopes of earlier detection and possible treatment.

Fifteen million Americans have the disease, and that number is expected to double as baby boomers age.

Being able to relate a gene mutation to the likelihood of developing the illness may lead to better tests and eventually treatments, the scientists hope.

"I don't think it's going to be a year or two ... but I'd guess less than 10 years" before a treatment might become available, said Albert O. Edwards, the lead researcher for one of three sets of researchers reporting on the link.

Macular degeneration causes the central region of the eye's retina to deteriorate, damaging or destroying vision. For now, there are no broadly effective treatments, though a recently approved drug can slow the disease for some patients.

The new gene findings are reported in separate papers in this week's online issue of the journal Science. The three research groups were led by Edwards, at the University of Texas Southwestern Medical Center, Josephine Hoh of Yale University School of Medicine and Margaret A. Pericak-Vance of Duke University Medical Center.

"Overall, this is a significant and novel finding," said Radha Ayyagari, a research investigator at the University of Michigan who studies age-related macular degeneration.

While one mutated gene is not the only factor in macular degeneration, the discovery "is an important finding and will help in identifying individuals at risk, provide information to design future therapies [and] understand the process of degeneration," said Ayyagari, who was not part of any of the three research teams.

The teams studied the genes of patients with AMD and others without the disease. Researchers found that people with a variation in the CFH gene were more likely to have the illness.

The CFH gene is involved in the production of a protein called complement factor H that helps regulate inflammation in a branch of the immune system.

The researchers said their study indicated as many as half of AMD cases in the elderly could be related to the gene variant.

Edwards, who is now the president of the Institute for Retina Research at Presbyterian Hospital of Dallas, noted that risk factors for AMD are similar to those for cardiovascular illness, including obesity, lack of exercise and smoking.

Pericak-Vance, director of the Duke Center for Human Genetics, said her study indicated that the gene variant could account for about 43 percent of the risk of developing AMD for older adults.

"This gene opens the door to a whole new understanding of the factors that contribute to this disease," she said in a statement. "The finding may ultimately lead to new methods for identifying those at high risk for macular degeneration and suggests new pathways for drug development."

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 were associated with the CFH gene variation.

Hoh, an assistant professor in the Department of Epidemiology and Public Health at Yale, reported that "Caucasian AMD patients are at least four times more likely to have one particular alteration in the CFH gene that produces a different form of the CFH protein, compared to individuals without the disease."

Dennis Schultz of Oregon Health and Science University, who two years ago identified a different gene involved in some cases of AMD, said the studies are an important finding, though not yet the whole story.

"It's complex, very difficult to understand, there are many genes involved and the environment plays a role as well," said Schultz, who was not part of the three study teams.

In December, the Food and Drug Administration approved the drug Macugen for treatment of the wet form of AMD. In studies for the drug, untreated patients had about a 45 percent chance of significant vision loss in a year compared with 30 percent for patients treated with Macugen. In addition, supplements including zinc and vitamins E, C and A have been shown to help some AMD patients.

The researchers was funded by the Raymond and Beverly Sackler Fund for the Arts and Sciences, the National Eye Institute, the National Institute on Aging, the National Center for Research Resources and Research to Prevent Blindness.

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