Oxygen Damage May Trigger Age-Related Blindness

Protein heaps in eye show signs of oxidative stress

MONDAY, Oct. 21, 2002 (HealthDayNews) -- Oxidized proteins that build up in the retina may be a missing link in the development of age-related macular degeneration, the leading cause of blindness in adults.

That's according to a new study that finds signs of oxidative stress in molecular waste heaps called drusen, which accumulate in the eyes of patients early in old-age blindness. While drusen haven't been proven to cause the condition, some researchers speculate they can slow the progression of the ailment by unmasking the content of these clumps and preventing their formation.

Age-related macular degeneration, or AMD, affects more than 10 million Americans over age 55. Roughly 10 percent of people have the "wet" form of the condition, in which an area beneath the retina is overrun by leaky blood vessels. This version accounts for 90 percent of cases of serious vision loss.

While everyone with AMD has drusen, not everyone with drusen gets AMD, says John Crabb, a Cleveland Clinic ophthalmologist and leader of the latest research.

"Nobody has proven that drusen has anything to do with AMD, but to most people it is the strongest risk factor," says Crabb, whose group reports their findings in tomorrow's issue of the Proceedings of the National Academy of Sciences.

The case for the role oxidative stress plays in AMD is similarly circumstantial but also fairly strong, Crabb says. The retina is an ideal place for oxidative damage because of its exposure to air and sunlight. The tissue is also rich in a substance called docosahexaenoic acid, a fatty acid especially vulnerable to the ravages of oxygen radicals.

Recent evidence has suggested a "supporting role" for oxidative damage in AMD, Crabb adds, including the finding that smokers are more prone to the condition and that in some people high doses of antioxidants -- like zinc and vitamins C and E -- can slow its advance.

In the latest study, Crabb and his colleagues dissected drusen from 18 people with healthy eyes and five with AMD. Using a technique called liquid chromatography to analyze the proteins, they found 129 different molecules, up to two-thirds of which were shared in normal and abnormal drusen. Many had never before been linked to the lumps.

Looking further, they saw structural signs of oxidative damage in some of the molecules, hinting that what makes good drusen go bad may be exposure to oxygen radicals.

Drusen accumulate on a structure in an area of the middle eye called the Bruch's membrane. The researchers saw that damaged proteins were more abundant in this region in AMD patients than in those with healthy retinas.

Some eye doctors are convinced that eradicating drusen can improve symptoms of AMD and they've taken to vaporizing the clumps with lasers. "The jury's still out" on that procedure, says Dean Bok, a vision expert at the University of California, Los Angeles School of Medicine. However, Bok, author of an editorial accompanying the journal article, says the new work adds much to what's known about the function of drusen.

In addition to these masses, Bok says, AMD is also marked by the accumulation inside eye cells of a substance called lipofuscin, or "old-age pigment." The two may prove connected, since they both appear to be generated by the same tissue layer, the retinal pigment epithelium.

What To Do

To learn more about age-related macular degeneration, visit the American Macular Degeneration Foundation or the AMD Alliance International.

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