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New Glaucoma Gene Discovered

Mutated protein linked to nerve damage

THURSDAY, Feb. 7, 2002 (HealthDayNews) -- A genetic discovery has provided at least a partial answer to a great puzzle about glaucoma, a leading cause of blindness in the United States, researchers say.

The research shows that a gene mutation can cause optic nerve damage, a finding that could lead to better methods of early detection and treatment of the condition, says Mansoor Sarfarazi, professor of human genetics at University of Connecticut Health Center and leader of the group reporting on the work in tomorrow's issue of Science.

Glaucoma, known as the "sneak thief of sight" because it arrives without symptoms, affects about 3 million Americans, half of whom aren't aware they have it, according to the Glaucoma Research Foundation. About 120,000 people are blind from the disease, which is much more prevalent among blacks than among whites. It is treatable if caught in time.

The most common form of glaucoma is the result of a progressive deterioration of the optic nerves, which carry signals from the eye to the brain, starting at age 40 or later. That deterioration is conventionally attributed to a buildup of excess fluid in the eye, resulting in increased pressure on the optic nerves. Glaucoma treatment centers on detecting this excess pressure, and giving medications to reduce that pressure.

However, a significant number of glaucoma patients, 30 percent or more, have normal intraocular pressure. Now, Sarfarazi and his colleagues report that mutations in a gene that codes for a protein they call optineurin can cause the optic nerve damage seen in glaucoma.

"We believed that not only intraocular pressure was involved in glaucoma," Sarfarazi explains. "There must be some protein circulating in the eye, which probably has a neuroprotective effect. We believe that the product of this gene has this effect. If the gene is mutated, over the decades of life, this protection becomes less and less. When it crosses a threshold, glaucoma results."

The gene was found by studying the genetic material of members of 54 families with a history of inherited glaucoma. The Sarfarazi team is doing a larger study, which will include more than 1,000 patients with all kinds of glaucoma, including the kind that occurs suddenly and early in life, to determine the exact role of optineurin in the disease.

It is a complex picture, Sarfarazi acknowledges. For example, 18 percent of the individuals in the initial study had the mutated gene and elevated intraocular pressure. However, Sarfarazi is already thinking about how the finding can be used to detect and treat glaucoma.

"Discovery of these mutations will help find those individuals who would not otherwise be diagnosed, which includes 50 percent of persons with familial glaucoma, and up to 70 percent of patients in Japan," he says. "As to treatment, we ultimately will identify a molecule, either synthetic or natural, that can substitute for the mutated form of the protein."

Sarfarazi says "some companies are interested in this technology," but he says it is too early to discuss any commercial implications.

The discovery is almost certainly just the beginning of identification of genes involved in glaucoma, says Michael A. Walter, associate professor of medical genetics and ophthalmology at the University of Alberta in Canada and co-author of an accompanying editorial.

"If a condition is rare, meaning 1 in 50,000, it is probably caused by a single gene," Walter says. "If it is extremely common, there are probably multiple causes. Today, we have already identified three genes that cause the purest form of glaucoma and other genes that are associated with an elevated risk of the condition."

The best known of those genes, designated TIGR, is associated with elevated intraocular pressure, Walter says. He is studying members of families with a rare form of inherited glaucoma in hopes of identifying other genes.

"Sarfarazi's group has found the most significant one to date, but any disease that has the same incidence as heart disease will have multiple causes," he says.

What To Do

Conventional testing for excess intraocular pressure is advisable for all older persons, Walter says. It is easily done and will detect most cases early, when treatment is most effective.

Basic information about glaucoma is available from the Glaucoma Research Foundation or the National Eye Institute.

SOURCES: Interviews with Mansoor Sarfarazi, Ph.D, professor, human genetics, University of Connecticut Health Center, Farmington; Michael A. Walter, Ph.D, associate professor, medical genetics and ophthalmology, University of Alberta, Edmonton, Canada; Feb. 8, 2002, Science
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