Oxidation May Be a Factor in Age-linked Eye Disease

By Merritt McKinney, Proceedings of the National Academy of Sciences

  October 21, 2002 

In an analysis of the tiny deposits of debris that accumulate in the eyes with age, scientists have uncovered more evidence that a process called oxidation is involved in age-related macular degeneration (AMD), an eye disease that is the leading cause of blindness among the elderly in developed countries.

"Our work establishes a molecular link between oxidative damage and AMD," the study's lead author, Dr. John W. Crabb of the Cleveland Clinic Foundation in Ohio, told Reuters Health.

Macular degeneration occurs when light-sensitive cells in the macula, the tissue at the center of the retina, breaks down. This can make it difficult to read, drive or perform other activities that require sharp vision.

The form of macular degeneration that occurs in adulthood, before old age, is caused by gene mutations, but a mix of genetic influences and environmental risk factors, including cigarette smoking, are thought to contribute to the type that occurs later in life, AMD. There is no cure for AMD.

With age, tiny deposits known as drusen can accumulate below the surface of the retina. High levels of drusen increase the risk of AMD, but little is known about what drusen are made of and how they form.

Crabb and his colleagues at the Cleveland Clinic developed a method of analyzing drusen, and they put it to the test in eyes from 16 AMD patients and 29 healthy individuals. Everyone in the study was at least 56 years old.

The investigators identified 129 proteins in the drusen samples. Although some of the proteins were found in both healthy eyes and those of people with AMD, 21 proteins were found only in drusen taken from diseased eyes. It is too soon to say whether these proteins are unique to AMD, according to the researchers. But it might be possible, they suggest in a report in the early online edition of the journal Proceedings of the National Academy of Sciences, that specific proteins found in drusen might be good targets for drugs to prevent or treat AMD.

"The mechanism of drusen formation is not known," Crabb said, but "the progression of AMD might be slowed if the formation of drusen could be therapeutically controlled."

In a finding that bolsters the idea that oxidation is involved in AMD, Crabb and his colleagues detected signs that some proteins found in drusen contained modifications that can result from oxidation, a process in which cell-damaging substances called free radicals accumulate. Oxidation is suspected of increasing the risk of heart disease, stroke and several other diseases.

Although these apparently oxidation-related modifications were present in samples from healthy people, too, they were more abundant in tissue from AMD eyes, Crabb said.

Others have suggested, Crabb said, that drusen form when "unknown signals" trigger immune system activity. "Our results," he said, "suggest that oxidative protein modifications may be the unknown signals that are causally involved in drusen formation."

The study had several sources of funding, including the National Institutes of Health, The Foundation Fighting Blindness and the pharmaceutical company Merck, Inc.