By Cassie Ferguson

Gazette Staff

Scientists have for the first time identified gene defects responsible for age-related macular degeneration, an incurable eye disease that steals the sight of one in four elderly Americans.

A research group including scientists from the Massachusetts Eye and Ear Infirmary (MEEI) found that one in six patients has a set of genetic mutations, a number significant enough to link the defects to the eye disorder. The researchers reported their findings in a recent issue of Science.

Pinpointing the gene responsible for the disorder will allow researchers to develop ways to identify people at risk for the disease. Those with the faulty gene could then minimize or even ward off the damage it causes. Co-author Johanna M. Seddon, associate professor of ophthalmology at MEEI, and associate professor of epidemiology at the School of Public Health, said, "Most importantly, our findings should lead to ways to prevent and treat this eye disorder that affects so many adults in their later years."

In the United States, age-related macular degeneration afflicts 11 million people, a number predicted to rise as baby boomers reach advanced ages. "As people live longer," Seddon said, "the disorder will become much more common."

Seddon said that while having the gene defects does not predict the severity of the disorder, people with parents who had the disease should try to minimize their risk. For example, they should avoid cigarette smoking, which is a known cause of the disease, as demonstrated by one of Seddon's studies last fall. Consumption of fatty foods, which may be linked to the disease, should be reduced, she said, while increased consumption of fruits and vegetables may be helpful.

Age-related macular degeneration gradually destroys the light-sensitive cells lining a region at the back of the eyeball called the macula. Without those cells, a blurry spot blocks the center of the sufferer's visual field. As the disease progresses, the spot spreads, obscuring all but peripheral vision. Although most victims don't lose their sight entirely, they can no longer drive, recognize faces, or read.

The disease occurs in two forms. In the more common "dry" version, yellow deposits build up at the back of the eye, disabling and killing the cells in the macula. About 20 percent of patients develop the more severe "wet" version, in which abnormal blood vessels scar the macula, ruining vision. In Seddon's study, the gene was linked almost exclusively to the dry form.

Neither form can be cured, though magnifying and telescopic lenses can sometimes improve the sight of people with the "dry" form. Laser treatment helps a small percentage of those with the "wet" form, but it only marginally improves or delays the damage.

The study followed up the discovery of a gene responsible for Stargardt's disease, a severe form of macular degeneration that strikes during childhood. Comparing the similarities of Stargardt's and age-related macular degeneration, the researchers suspected the same gene might be responsible for both.

Their hunch turned out to be correct, though the diseases correlate to different parts of the same gene. Of the 167 patients in the age-related study, 26 had the gene defects. Seddon's previous research had demonstrated that the disease aggregates in families. "Now we have proof of a genetic link," said Seddon. For those without the mutations, the researchers surmised that other genes and environmental factors such as cigarette smoking and diet may lead to the disease.

Researchers at the Massachusetts Eye and Ear Infirmary, the Medical School, Baylor College of Medicine in Houston, the National Cancer Institute in Bethesda, and the University of Utah in Salt Lake City collaborated on the study.

Finding the gene defects is far from the end of the search for the scientists, who have already started looking into the precise role of the defects in macular degeneration. "There's clearly more work to do," said Seddon, who has been studying the disease for 12 years, "and we've now reached an exciting crossroads in our investigation."