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From St. Louis Post-Dispatch, Monday, Aug. 14, 2006, by Tina Hesman Saey

Scientists at Washington University have made a key discovery in a disease that is the leading cause of blindness in people over age 65.

The research also may have implications for vision loss associated with diabetes and premature birth.

The new study shows that an immune-system protein controls blood-vessel growth in the eye. Abnormal blood-vessel growth is an important step in the blinding disease called age-related macular degeneration. The protein could be a target for treatments to prevent the disease.

The picture above shown abnormal blood vessels and hemorrhage underneath the retina in the wet form of age-related macular degeneration.

Abnormal blood vessels and hemorrhage underneath the retina in the wet form of age-related macular degeneration.

Results of the new study, led by Dr. Rajendra S. Apte at Washington University, appear on-line in the August issue of the journal PLoS Medicine, a publication of the Public Library of Science.

Age-related macular degeneration affects the central part of the retina, called the macula. It is the part of the eye responsible for the central field of vision. The area around the macula provides peripheral vision. The disease has two stages, "dry" and "wet."

People with macular degeneration first go through the dry stage of the disease. It affects about 7 million people in the United States. In that phase, yellow deposits of pigment, called drusen, form under the macula. The clumps grow slowly and lead to gradual loss of vision.

As the disease progresses, abnormal blood vessels "sprout like little weeds" under the retina in the areas where the pigment clumps are found, Apte said. The blood vessels leak and damage the retina, leading to sudden and dramatic loss of vision. About 1 million people in the U.S. are blind from the disease and 100,000 to 200,000 people each year are diagnosed with it.

Laser therapies and drugs injected directly into the eye are now used to treat macular degeneration. The treatments stop blood vessels from growing and keep the disease from progressing. In about one-third of patients, some vision is restored.

Another 30 percent of patients continue to lose their sight, with about 5 percent experiencing severe loss of vision even after the treatments, said Dr. Robert Bhisitkul, an associate professor of clinical ophthalmology at the University of California, San Francisco. In order to stop the disease, scientists need to understand how it starts.

"We understand pieces of the disease, but I'd say we don't understand most of it," Bhisitkul said.

Researchers have had clues that the immune system might be involved in regulating the growth of blood vessels in the eye, said Dr. Peter Gehlbach, a retina specialist at the Wilmer Ophthalmological Institute at Johns Hopkins University School of Medicine in Baltimore. Some studies suggested that the immune system prevents blood vessels from growing into the eye. Others suggested the opposite _ the immune system promotes blood-vessel growth, he said.

"There was never any clear checkmate winner," Gehlbach said.

The Washington University team used a laser to create a defect in the eyes of mice. Blood vessels then could grow into the area, mimicking macular degeneration. The researchers measured blood-vessel growth in mice lacking certain immune-system proteins.

Mice lacking an anti-inflammatory protein called interleukin-10 (IL-10) had fewer blood vessels invading the retina, and more immune cells called macrophages. Injecting more IL-10 into the eyes increased blood-vessel growth, but injecting macrophages reduced their formation.

Those results mean that macrophages help protect the retina from abnormal blood vessels, but IL-10 blocks the macrophages' protective action. That turns thinking about the way macrophages affect blood-vessel growth on its head, said Dr. Quan Dong Nguyen, also of Johns Hopkins University.

Macrophages are cells that promote inflammation, which scientists have long thought would cause blood vessels to grow. But the new result shows that macrophages and IL-10 affect blood-vessel growth in the opposite direction from what anyone previously thought. The result is "important and extremely novel," Nguyen said.

If researchers can learn to control IL-10, they may be able to develop new drugs that could prevent dry macular degeneration from converting to the blinding, wet form, Bhisitkul said.

The finding also may apply to tumors and other places where abnormal blood vessels develop, Gehlbach said. Some researchers have found evidence that IL-10 may influence blood-vessel growth in the eyes of people with diabetes and in premature babies, Apte said.

The researchers don't yet know whether people with macular degeneration have alterations in IL-10 or if the protein's production changes with age, Apte said.


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