There was good news recently for the 6 million older Americans whose visionis being threatened or destroyed by the disease macular degeneration.
Researchers from the Massachusetts Eye and Ear Infirmary and three other institutions reported in the Sept. 22 journal Science that they had found a cluster of genetic mutations that appear to cause about a sixth of all age-related macular degeneration, or AMD. The mutations 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.
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 also might allow scientists to test prevention strategies in these people and alert them to avoid known risk factors such as smoking, fatty diets and exposure to ultraviolet light.
Though genetic testing would be too expensive for the near future, Gerald 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,” Chader said. “If people are getting this disease at 60 and we could learn how to slow it by, say, 20 years, that would be a cure.”
The Washington-based foundation is the largest non-governmental supporter of research on degenerative diseases of the retina.
The researchers who discovered the mutations are based at the National Cancer Institute in Frederick, Md., Baylor University in Texas, the University of Utah and the Massachusetts Eye and Ear in Boston.
They are 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 his 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 was inherited, but the new research is the first concrete 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 at Massachusetts Eye and Ear.
She is a co-author of the paper and provided blood samples for DNA analysis from members of New England families with a history of macular degeneration.
She cautioned the gene finding doesn’t directly point to a treatment or predict how severe the disease might be in someone with the 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 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 might become legally blind because their central vision is so poor, but they don’t become totally blind: Their peripheral 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 Frederick Cancer Research and Development Center, followed up that lead and discovered that 13 mutations of the same gene cause age-related macular degeneration.
Chader said the finding was a needed morale booster because scientists and physicians have largely been stymied in efforts to treat or prevent the disease.
At a recent conference in Boston, about 40 eye specialists and researchers discussed the discouraging results of several experimental treatments aimed at halting or preventing
the blood vessel growth in wet macular degeneration.
The meeting followed an unexpected report in July showing that the drug alpha interferon did not block the blood vessel growth. Earlier experiments had suggested it would.
“We were shocked,” said Dr. Robert D’Amato, an ophthalmologist at Harvard Medical School and Children’s Hospital in Boston who headed the meeting sponsored by International Business Communications Group.
