WEDNESDAY, Aug. 27 (HealthDay News) -- Scientists from the United States and China have identified the first gene directly associated with the onset of severe "dry" macular degeneration, one of two forms of age-related macular degeneration that currently threatens the vision of up to nine million older Americans.
The discovery, based on work with both human and mice cells, centers on a specific immune system protein called TLR3. Although helpful in fending off illness when confronted with certain viral infections, this molecule, when routinely activated, was also found to raise the risk for "dry" macular degeneration by attacking infected retinal cells.
But, the study authors also found a genetic silver lining in the form of a mutated version of TLR3 -- a so-called "inactive" or "less active" TLR3 -- that suppresses this retinal death process, seemingly protecting people from the eye disease.
"This represents a major step forward in our understanding of the dry form of macular degeneration," said study co-author Dr. Kang Zhang, a professor of ophthalmology and human genetics at the Shiley Eye Center at the University of California, San Diego, School of Medicine. "And with the identification of this potential target, we can try to develop treatments for a disease which, for the moment, we can't treat."
The findings were expected to be published online Aug. 28 in the New England Journal of Medicine.
But celebration over isolating TLR3's role in dry age-related macular degeneration (AMD) has been tempered by some potentially troubling implications that the new findings seem to have for a cutting-edge investigational treatment recently unveiled to target the so-called "wet" form of AMD.
The treatment in question, known as "RNA interference," or RNAi, works by "silencing" genes that bring about wet AMD. Unfortunately, the treatment appears to simultaneously activate TLR3 -- resulting in a 60 percent spike in retinal cell death among mice and humans genetically susceptible to developing dry AMD. The result: RNAi may help protect against wet AMD while boosting the risk for dry AMD, the study authors said.
"This raises particular concerns regarding RNAi therapy for wet AMD," Zhang said. "But by establishing this link between the treatment for the wet form of AMD and the potential harmful effect on the dry form of the disease, we can perhaps better understand the mechanisms of both diseases."
Age-related macular degeneration is the leading cause of blindness in adults over the age of 60, according to the U.S. National Eye Institute. The progressively worsening disease affects the macula portion of the eye, located in the center of the retina, which enables detailed vision.
The disease can strike in two ways: wet and dry. In its wet form --sometimes referred to as "advanced AMD" -- loss of vision occurs rapidly due to the growth of abnormal blood vessels under the macula, leading to leakage of blood and fluids. In its more slowly progressing dry form, light-sensitive macular cells begin to break down, leading to a blurring of vision in one or both eyes, according to the eye institute.
Addressing the new findings, Rando Allikmets, a professor of ophthalmology, pathology and cell biology at Columbia University, urged restraint.
"I think these results have to be taken with caution, because the association effect of TLR3 with AMD is very small when compared to the disease's association with some other genes," he said. "And there has been already one study saying there is absolutely no association of the TLR3 genetic variant with AMD. So, this raises a question and a need for further edification. It could be that this is just a spurious finding, and there is, in fact, no association with AMD."
For more on age-related macular degeneration, visit the National Eye Institute.
SOURCES: Kang Zhang, M.D., Ph.D., professor of ophthalmology and human genetics, Shiley Eye Center, University of California, San Diego; Rando Allikmets, Ph.D., professor, ophthalmology, pathology and cell biology, Columbia University, New York City; Aug. 28, 2008, New England Journal of Medicine, online