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Age-related macular degeneration is the leading cause of blindness in people over the age of 65, and it affects more than 10 million people in the United States. The disease erodes the macula, the center of the retina, slowly eclipsing central vision and potentially causing blindness. Currently, there is no treatment for dry macular degeneration, the most common form, in which more and more cells within the macula slowly die off.

Now a team of researchers from multiple institutions, including the Shiley Eye Institute, at the University of California, San Diego (UCSD), have identified a genetic link associated with dry macular degeneration, which they say may lead to treatments for the debilitating disease. However, they caution that an experimental therapy for another form of macular degeneration may cause adverse effects in patients who possess the genetic variant.

Kang Zhang, a professor of ophthalmology and human genetics at UCSD, led the study, which is published in the online edition of the New England Journal of Medicine. In their experiments, Zhang and his colleagues zeroed in on the genetic expression of a key molecule involved in the body’s immune response. This molecule, called tlr3, jumps to action in the presence of RNA, which can take the form of invading viruses. As part of the immune response, the molecule kills infected cells, preventing the virus from spreading further. But in some cases, this defense can go haywire in the eye.

The molecules’ “role in life is to kill cells to protect the universe around healthy cells,” says Nico Katsanis, Zhang’s collaborator on the study and an associate professor of ophthalmology, molecular biology, and genetics at the Johns Hopkins School of Medicine. “But if they are too sensitive towards viral insults, they might kill cells a little too eagerly, and that might be a predisposing factor that leads to macular degeneration.”

The group hypothesized that a gene that increases the activity of tlr3 may in fact lead to overeager cell death in response to RNA and viruses, and it may increase a person’s risk for dry macular degeneration.

To investigate this potential link, the team first performed a genetic association study, and obtained blood samples from three groups of patients, each with a different form of macular degeneration, including those with wet macular degeneration, a severe form characterized by an overgrowth of blood vessels behind the retina. The researchers also included more than 300 samples of unaffected controls.

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Credit: Kang Zhang/UCSD

Tagged: Biomedicine, genetics, blindness, macular degeneration, eye disease, vision loss

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