Genetic Role Seen in Chief Cause of Blindness

Mutations tied to age-related macular degeneration

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HealthDay Reporter

WEDNESDAY, July 21, 2004 (HealthDayNews) -- For two decades, scientists have suspected that genes may play a role in the development of age-related macular degeneration (AMD), the leading cause of blindness in the developed world.

Now researchers have found that mutations in a specific gene are sometimes associated with the vision-robbing disease.

"This gene causes 1.7 percent of what a well-trained clinician would call 'typical' macular degeneration," said Dr. Edwin M. Stone, director of the Center for Macular Degeneration at the University of Iowa. His report appears in the July 22 issue of the New England Journal of Medicine.

"This we think will lead us to an understanding of a mechanism of the disease," he said, emphasizing it is probably only one of several mechanisms. AMD may actually be 50 different diseases, said Stone, who is also investigator at the Howard Hughes Medical Institute at the University of Iowa.

In AMD, deposits of fat and protein accumulate in the eye, affecting the part of the back of the eye called the macula, which is the central part of the retina. It can cause the central part of vision to become blurry or wavy and can also result in a blind spot. AMD often strikes those aged 60 and older, but a rare, inherited form strikes about 20 years earlier, Stone said.

Stone's team studied 402 patients with age-related macular degeneration and 429 patients without the problem. They took blood samples from the subjects, then extracted DNA to examine it for variations in genes that code for proteins called fibulins.

Previous research by Stone and his colleagues had found a mutation in the fibulin 3 gene in a disease resembling AMD. In the current study, "we looked at fibulin 1, 2, 4, 5 and 6," Stone said. "We asked what changes in these five fibulin genes were found in people with AMD and the controls. In virtually all the genes, we found changes in the macular degeneration patients, but we also found them in the controls."

But in the case of fibulin 5, Stone's team found changes in the AMD patients but not the controls.

Seven of the 402 AMD patients each had a different change in the fibulin 5 gene that wasn't found in the healthy subjects. Six of the seven changes changed an amino acid in the fibulin 5 protein.

Next, Stone's group will repeat the study in another large group of patients to see if the findings hold up.

Another expert calls the finding a potential small clue to the puzzle of AMD. But just seven of the patients were found to have the variant, and that is a fairly small number, said Dr. Richard Bensinger, a spokesman for the American Academy of Ophthalmology.

That misses the point, countered Stone. An estimated 7 million people in the United States alone have AMD, and 1.7 percent of that -- approximately 119,000 -- is still a significant number.

Bensinger said further research may add weight to the finding, and noted that it is a new avenue of research. "No one has looked at this before -- mutations in the fibulin 5 gene," he said.

But additional research is crucial, Bensinger added: "All of this may be meaningless information. There may be no inheritance going on at all."

Even if the finding doesn't hold up, Bensinger noted, "this may be a stimulus for researchers to look at this whole set of proteins" and find out other clues to the disorder."

For now, Stone said, it's important for people to understand this is a laboratory finding at the moment.

"This does not mean you should have any sort of genetic testing right now," he said. "Although we are hopeful that this discovery will lead us closer to treatment, there is no specific new treatment based on this finding."

More information

To learn more about macular degeneration, visit Prevent Blindness America.

SOURCES: Edwin M. Stone, M.D., Ph.D., professor of ophthalmology and director, University of Iowa Center for Macular Degeneration, and investigator, Howard Hughes Medical Institute, University of Iowa, Iowa City; Richard Bensinger, M.D., spokesman, American Academy of Ophthalmology and Seattle ophthalmologist; July 22, 2004, New England Journal of Medicine

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