Gene link to eye disease is found Health: Rare progress in fighting macular degeneration is built on earlier discovery at Hopkins.

October 14, 1997|By Richard Saltus | Richard Saltus,BOSTON GLOBE

In yesterday's Today section, the location of the headquarters of The Foundation Fighting Blindness was misidentified. The foundation is in Hunt Valley.

The Sun regrets the error.

For the 6 million older Americans whose vision is being threatened or destroyed by a disease called macular degeneration, and for the doctors who have long been frustrated in their efforts to treat it, last month brought a rare dose of good news.

Researchers from the National Cancer Institute in Frederick and three other institutions reported in the journal Science that they had found a cluster of genetic mutations that appear to cause about one-sixth of all age-related macular degeneration, or AMD. The mutations all affect the same gene, which the researchers were able to pinpoint.


Other undiscovered genes and environmental factors probably are involved in the other 5 million cases of AMD, they said, but the discovery represents the first major advance against the vision-damaging disease, which in developed countries leaves more people legally blind than any other cause.

Discovery of the mutations could lead to a test to identify people at high risk before the disease process begins. It may also allow scientists to test prevention strategies in these people and alert them to avoid known risk factors like smoking, fatty diets and exposure to ultraviolet light.

Though genetic testing would be too expensive for the near future, Gerald J. Chader, chief scientific officer for The Foundation Fighting Blindness, said the gene find is "a blockbuster."

"Now that we know the gene and can begin understanding what the protein is doing, we can possibly design some drug interventions," said Chader. "If people are getting this disease at and we could learn how to slow it by, say, 20 years, that would be a cure!"

The Washington-based foundation is the largest nongovernmental supporter of research on degenerative diseases of the retina.

The researchers who discovered the mutations are based at the National Cancer Institute, Baylor University in Texas, and the University of Utah, as well as the Massachusetts Eye and Ear Infirmary in Boston. They are now studying the mutant gene for clues to the nature of the protein it causes to be produced. They believe the protein plays a major role in destroying the macula, the critical central portion of the retina.

When the disease strikes, the light-sensitive cells in the macula begin to atrophy and fail, often leaving a blank space in the center of a person's visual field.

"It robs the patient of the most important part of their vision that is needed for driving, reading and recognizing faces," said Dr. Norman Zabriskie, a University of Utah ophthalmologist and one of the authors of the Science paper.

Because it sometimes runs in families, scientists had suspected that at least some macular degeneration is inherited, but the new research is the first proof.

Linking the disease to a particular gene "is a giant step forward in understanding the ultimate mechanism of why people get this disease," said Dr. Johanna Seddon, an ophthalmologist and epidemiologist. She is an author of the paper and provided blood samples from members of New England families with a history of macular degeneration for DNA analyses.

But she cautioned the gene finding doesn't directly point to a treatment or predict how severe the disease might be in someone with the gene mutation.

The great majority of affected people have the so-called "dry" form, in which flecks of yellow material, called "drusen," form on the surface of the retina, and some vision cells subsequently begin to atrophy.

Only 10 to 15 percent have the most serious form, known as "wet" macular degeneration, caused by inappropriate growth of blood vessels under the retina at the back of the eye. The vessels leak fluids and buckle the light-sensitive cells of the retina, much as tree roots can lift and distort a section of pavement.

People with this form of the disease may become legally blind because their central vision is so poor, but they don't become totally blind: their peripheral, or side, vision usually remains. The "wet" form also progresses much faster.

The scientists homed in on the gene mutations after Dr. Jeremy Nathans and colleagues at the Johns Hopkins School of Medicine reported last March that they had found a mutant gene for Stargardt disease, a rare genetic disease that causes macular degeneration in children and young adults.

A consortium of scientists led by Michael Dean at the NCI's Frederick Cancer Research and Development Center followed up that lead and discovered that different mutations of the same gene -- 13 of them in all -- cause age-related macular degeneration.

Attempts to stop the invading blood vessels with radiation, lasers, anti-angiogenesis drugs, monoclonal antibodies and other means have proven unsuccessful or haven't been tested enough to show whether they work.

"We're really in the dark ages with this condition, but there are little glimmers of light," said Dr. Allen C. Ho, an ophthalmologist at the University of Pennsylvania School of Medicine who headed a laser treatment study.

The success of lasers in treating diabetic retinopathy, in which blood vessels proliferate on the front of the retina, rather than behind it, led to hopes that the high-energy light beams could be used to destroy vessels in more macular degeneration. The problem, said researchers, is that because the vessels grow behind the retina, laser bursts to destroy the blood vessels also destroy vision cells.

Pub Date: 10/14/97

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