Sight for sore eyes: a glaucoma gene.

A decade after they began studying a family plagued by an aggressive form of the eye disorder glaucoma, researchers have identified the mutant gene responsible. The scientists estimate that mutations in this gene may account for nearly 10 percent of all cases of glaucoma, including an estimated 100,000 in the United States.

"This is a treatable disease, and the hope is that this [discovery of the gene] will make it possible to find patients who need to be treated," says Val C. Sheffield of the University of Iowa College of Medicine in Iowa City.

Sheffield and his colleagues had been looking for the gene since the mid-1980s, when a glaucoma patient named Alan Rogers walked into their -ffices and described how the disease had affected five generations of his family. By studying the DNA in blood samples from this family, the Iowa group narrowed its gene search to a small span of chromosome 1 (SN: 6/12/93, p. 376).

Glaucoma takes on many forms and is the second most common cause of blindness in the United States. Though it strikes most people in their 50s and 60s, some families, such as Alan Rogers', suffer from juvenile open-angle glaucoma, which can begin in the teens.

Like other glaucomas, this early-onset form results from elevated pressure inside the eye. The pressure damages the optic nerve, which carries visual information to the brain. Glaucoma patients suffer gradual loss of peripheral vision and can ultimately go blind.

"Glaucoma is a disease that's insidious. You often don't know you have it until it's really advanced," notes Janey L. Wiggs of the New England Eye Center in Boston. Caught early, however, glaucoma-induced vision loss can usually be prevented by surgery or drugs that lower pressure inside the eye.

In most cases of glaucoma, pressure builds up because the eye cannot properly drain away the clear fluid that circulates through the front of the organ, bathing the lens and cornea. This fluid normally flows out of the eye through a drainage system called the trabecular meshwork.

Several years ago, Jon R. Polansky and Thai D. Nguyen of the University of California, San Francisco isolated a gene that is active in the trabecular meshwork and the ciliary body, the ocular structure that makes the clear fluid.

Working with the UCSF pair, Sheffield and his colleagues have now found that this gene is located in the same chromosome 1 region they had already pinpointed and that it is mutated in several families with juvenile open-angle glaucoma, including Rogers'. In the Jan. 31 Science, they also report finding mutations in the gene, now called GLCA1, in a family beset with adult-onset glaucoma and in a few glaucoma patients with no obvious family history of the disease.

GLCA1 mutations may be too rare to make widespread gene testing practical. In glaucoma-prone families whose disease traces to chromosome 1, however, members would probably benefit from having the gene examined. "We can tell at birth who in that family is going to get glaucoma," says Wallace L.M. Alward of the University of Iowa.

Further research, he adds, should reveal GLCA1's role in regulating eye pressure, suggest new ways to combat glaucoma, and point to genes causing other forms of the disease.