A team of scientists, including a researcher from the University of Kentucky, has identified a gene that is directly related to an incurable eye disease that affects more than 8 million Americans. The discovery might be the first step toward a treatment for the disease, which causes permanent vision loss.
The researchers, who will report their results Thursday in the online edition of the New England Journal of Medicine, identified a link between toll-like receptor 3 (TLR3), a protein that alerts the body's immune system to infections, and the dry form of age-related macular degeneration (AMD).
"This is yet another breakthrough in our continuing appreciation that AMD is a genetic disease," said Dr. Philip Rosenfeld, a professor of ophthalmology at the Boscum Palmer Eye Institute at the University of Miami. He was not involved in the study.
The study also identified a mutated form of TLR3 that protects against dry AMD. That mutation might point to a treatment, said Dr. Jayakrishna Ambati, a retinal surgeon in UK's Department of Ophthalmology and Visual Sciences.
When TLR3 is activated, it causes infected cells to die.
"If you have this mutation, your TLR3 gene doesn't work properly," Ambati said. "These people are protected."
Researchers suspect that a virus triggers TLR3.
Ambati led the study — which used human and mouse models — along with Dr. Kang Zhang, a professor of ophthalmology and human genetics at Shiley Eye Center at the University of California, San Diego, and Nicholas Katsanis, a professor of ophthalmology, molecular biology and genetics at Johns Hopkins School of Medicine.
The study is significant because it is the first to link a specific gene with a specific form of AMD, said Dr. Hemin Chin, director of the Ocular Genetics Program for the National Eye Institute. Chin cautioned, however, that the study's results would need to be replicated.
"One report by no means will lead to any kind of diagnostic, treatment strategies," Chin said. "This is the first step toward getting to that point."
The National Eye Institute is one of many funding providers for the project.
The results also suggest that RNA interference, a type of treatment that is now in clinical trials for the wet form of AMD, might "turn on" TLR3 in some people, causing dry AMD, Ambati said.
Rosenfeld said that it was premature to assume that short-interfering RNAs, as the drugs are called, would predispose people to dry AMD. The risk should be tracked but it doesn't negate the potential of the drugs, he said.
"We must await the study results before jumping to any conclusions," said Rosenfeld, who is doing phase I clinical trials for an siRNA.
Ambati raised questions about siRNAs in another paper published this spring in the British journal Nature. That paper reported that siRNAs, a class of drugs that are supposed to "silence" or prevent expression of a gene, don't work as originally thought. Ambati's research suggests that drugs for wet AMD prevent blood vessel growth not only in the eye but also elsewhere in the body.
Ambati is working on a drug that would inhibit the expression of TLR3. The first phase of clinical trials could begin as early as next year.