Genetic Clue Found To The Leading Cause Of Blindness In The United States

"I first noticed it about 15 years ago," said Oster, who lives in a rural area northwest of Portland. "I was trying to type a paper, and it just took tremendous effort to see the letters. The spot would move wherever I was trying to read." Now, Oster is unable to drive at night and she struggles to read music when playing the violin, one of her favorite activities. New research by a team at the Macular Degeneration Center at Oregon Health Sciences University's Casey Eye Institute shows the disease that's blurring Oster's vision has a genetic cause. The research was done in collaboration with scientists at the Laboratory of Statistical Genetics at Rockefeller University in New York.

Like Oster, millions of Americans suffer from a gradual fading-out of central vision known as age-related macular degeneration. Roughly 7 percent of Americans older than 75 have progressed to the late stage of the disease. The loss of vision comes from deterioration of a particularly sensitive area of the retina called the macula. The team of scientists has zeroed in on the location of a gene that causes an inherited form of the disease. Details of this research appear in the August edition of the Archives of Ophthalmology.

The team of researchers, led by Michael Klein, M.D., professor of ophthalmology at OHSU, studied 21 individuals from Oster's family; 10 of them with age-related macular degeneration.

"It has been difficult to find a genetic cause for this disease," said Klein. "It has a late age of onset, can take one of several forms and is difficult to diagnose early. By studying a large family affected by the disease, we could compare genetic information from family members and determine differences between affected and unaffected individuals."

The researchers employed a technique called "linkage analysis" to zero in on the location of the macular degeneration gene. The technique involves comparing short segments of DNA from affected and unaffected individuals. The affected individuals share variations in their genetic material that are not found in the general population.

"Starting with a genome-wide search, we narrowed down the location of the gene in this family to an area of chromosome 1," said Dennis Schultz, Ph.D., a research assistant professor of ophthalmology at OHSU. Specifically, the gene is located in an area referred to as chromosome 1q25-q31.

"It's a little like finding out the gene is living along a certain street, but not knowing which house it's in," said Schultz. "Further research will focus on uncovering the exact street address of the gene." Previous research has focused on a gene in a different area of chromosome 1 that causes a juvenile form of macular degeneration and also may be associated with age-related macular degeneration. But this is the first published research to identify the location of a genetic defect in a large family with age-related macular degeneration.

Age-related macular degeneration has been a major focus of genetic research both because it is so common and because it is so difficult to treat. The most effective current treatment is a technique called laser photocoagulation, in which a laser beam is used to slow down the so-called "wet" form of the disease. In this form, new blood vessels grow underneath the retina, than leak, bleed and form scar tissue. The degeneration process usually occurs rapidly, over weeks or months, and often profoundly affects central vision. But the wet form accounts for less than 20 percent of cases, and there is no treatment for "dry" age-related macular degeneration. The dry form of the disease results from progressive damage to the pigment cell layer of the retina. Vision loss occurs slowly, usually over years, and is less severe than that caused by the wet form of the disease. The ability to do genetic screening for the disease could help physicians anticipate which patients are at risk and take early preventative measures to head off a significant loss of vision. An ultimate goal of the research is to develop measures and therapies that can eliminate age-related macular degeneration.

"We believe this genetic research will help us accomplish this goal by leading us to a better understanding of the basic cause of the disease," said Klein.

Ruth Oster said she's glad her family was able to be part of this discovery, even though a cure for the disease may still be far off. "The whole family has sort of accepted it," she said. "It would be great if I can continue to play music and keep passing the driver's exam. And it's good to know that eventually they'll find a way to slow down or stop this disease."

The Macular Degeneration Center is interested in studying other families with a high incidence of age-related macular degeneration.

This study was supported by the George and Carolyn Goodall Foundation, the Joseph E. Paquet Fund, the Frances and Monroe Jubitz Fund, the Macular Degeneration Center Fund, the Collins Medical Trust, an unrestricted grant from Research to Prevent Blindness, the Foundation Fighting Blindness, the Heed Foundation and the Medical Research Foundation of Oregon.

In addition to Klein and Schultz, investigators on this project were Ted Acott, Ph.D.; Blair Berselli; Albert Edwards, M.D., Ph.D.; Richard Weleber, M.D.; and Mary Wirtz, Ph.D.; all of Oregon Health Sciences University. Also included are Tara Matise, Ph.D., and Jurg Ott, Ph.D., of the Laboratory of Statistical Genetics at Rockefeller University.