Genes shed light on common blindness cause.

Newly identified genes responsible for two rare, degenerative diseases of the retina could help researchers target the cause of age-related macular degeneration, an eye disorder that constitutes the leading cause of blindness among older individuals in developed countries.

Two independent groups of researchers have pinpointed the genes that, when altered, lead to Best's disease and North Carolina macular dystrophy--two inherited forms of macular degeneration that affect individuals early in life. A team led by ophthalmologist Edwin M. Stone and pediatrician Val C. Sheffield of the University of Iowa in Iowa City report in the July NATURE GENETICS that the Best's disease gene lies on chromosome 11. In the July GENOMICS, researchers led by ophthalmologist Kent W. Small of Duke University in Durham, N.C., report tracing the North Carolina macular dystrophy gene to chromosome 6.

Macular degeneration is a group of largely untreatable disorders characterized by destruction of the macula, the central portion of the retina responsible for fine visual detail. Patients with age-related macular degeneration often develop progressively widening distortions or blank spots in their vision, beginning in their 50s or 60s. According to the National Eye Institute, each year 16,000 people in the United States with age-related macular degeneration become legally blind, which means that eyeglasses cannot correct their vision.

In Best's disease, the macula becomes coated with a yellowish substance called lipofuscin, which obstructs progressively larger regions of the retina as an individual ages. Researchers estimate that this inherited disorder causes only 1 percent of all cases of macular degeneration. However, they cannot accurately assess the prevalence of Best's disease because many cases are misdiagnosed as age-related macular degeneration.

The Iowa researchers found the gene responsible for Best's disease by analyzing DNA taken from 45 members of a five-generation family with 29 Best's disease patients. By comparing the DNA from affected and unaffected family members, they narrowed down the genetic defect responsible for the disorder to a specific region on the long arm of chromosome 11.

The Duke researchers used a similar strategy to pin down the gene for North Carolina macular dystrophy, which affects 96 members of various ages from a single large family whose ancestors first settled in that state in 1830. Small and his colleagues pinpointed the cause of this early-onset form of macular degeneration to the long arm of chromosome 6.

The discoveries are the first steps toward developing tests and treatments for Best's disease and North Carolina macular dystrophy, says Iowa's Stone. But even more important, he adds, the findings will lead to a better understanding of all types of macular degeneration, of which he estimates "well over 50 percent" have a genetic cause.

"We want to find five or six different genes that affect the central retina and then see how they relate to age-related macular degeneration," Stone says.

Duke's Small agrees that the new genes "could have far-reaching ramifications for age-related macular degeneration and other, similar eye disorders." --C. Ezzell