LA JOLLA
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An international team led by a UCSD eye researcher has found the first genetic link to dry age-related macular degeneration, the most common form of progressive blindness.
A study by the team describes a genetic variant in about 66 percent of the population that appears to protect people from certain kinds of viral damage, a leading suspect in the development of the eye disease. People who lack this variant are not protected and thus more vulnerable to dry macular degeneration.
The discovery was spearheaded by Dr. Kang Zhang of the Shiley Eye Center at the University of California San Diego School of Medicine in La Jolla.
About 900,000 people in the United States have been diagnosed with dry macular degeneration, and up to 10 million are at risk.
In a separate finding, Zhang's study sounds a warning for makers of some drugs being used in clinical trials for treatment of other diseases, including wet age-related macular degeneration, the same type of blindness caused by a different process.
These experimental medications, which spur a phenomenon called RNA interference, or RNAi, may suppress a process that helps protect people from dry macular degeneration, Zhang said.
“Ironically in some individuals, using RNAi to cure wet age-related macular degeneration might actually increase the risk” of getting dry macular degeneration, he said.
The study by Zhang and his colleagues is being published today in the online edition of the New England Journal of Medicine. The release date was moved up from October because of the study's possible implications for the safety of the RNAi clinical trials.
Zhang collaborated with researchers from institutions such as the Utah School of Medicine, Johns Hopkins University in Maryland and Sichuan Academy of Medical Sciences in China.
Experts at the National Eye Institute, which helped fund Zhang's work, expressed cautious enthusiasm for the findings.
This paper “is the first to implicate a specific genetic variation” that might lead to age-related macular degeneration, said Hemin Chin, the institute's acting director in ocular genetics.
But Chin said its conclusions are preliminary and should not be used to cancel or curtail clinical trials that use RNAi technology. In science, Chin said, a discovery “has to be confirmed, and confirmed, and confirmed.”
The UCSD-led report contains no data regarding RNAi, said Antonin de Fougerolles, senior research director for Alnylam Pharmaceuticals, a company in Cambridge, Mass., that makes an RNAi compound being used in a clinical trial for respiratory viral infections.
“It doesn't add any information to the applications of RNAi therapeutics in eye diseases or elsewhere,” de Fougerolles said.
Dry age-related macular degeneration is a relatively slow disease process that accounts for 90 percent of all cases of macular degeneration. It causes blurred central vision and erosion of detail, impairing the ability to read or see small objects. Straight lines may appear warped.
All this occurs because over time, tiny proteins called drusen accumulate beneath photoreceptors, which are light-sensing cells in the macula that convert light to electrical impulses so they can be transferred through the optic nerve to the brain. Drusen somehow damage photoreceptors, leading to loss of vision.
It's thought that viruses work with the drusen to bring about the disease.
Wet age-related macular degeneration is usually more severe than the dry form and can develop more rapidly. Damage is caused by abnormal growth of blood vessels that leak blood and fluid into the macula.
Cheryl Clark: (619) 542-4573; cheryl.clark@uniontrib.com
