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New Discovery: Trigger for Macular Degeneration

view through eye with central vision obscured

Researchers at University of Virginia School of Medicine have discovered an important trigger for the inflammation causing macular degeneration. Dr. Jayakrishna Ambati, vice chairman for research in UVA’s Department of Ophthalmology and the founding director of UVA’s Center for Advanced Vision science, and Nagaraj Kerur, assistant professor in the Department of Ophthalmology, and their laboratories have determined that the culprit is an enzyme called cGAS. Findings were published in the scientific journal Nature Medicine.

Ambati noted that almost 200 million people in the world have macular degeneration. “For the first time,” he noted in a UVA today article, “we know in macular degeneration what is one of the very first events that triggers the system to get alarmed and start, to use an anthropomorphic term, hyperventilating. The overdrive of inflammation is what ultimately damages cells, and so, potentially, we have a way of interfering very early in the process.

The enzyme cGAS plays an important role in the body’s immune response to infections by detecting foreign DNA. It surprised the researchers to learn that cGAs has a role in the dry form of age-related macular degeneration.

“It’s really surprising that in macular degeneration, which, as far as we know, has nothing to do with viruses or bacteria, that cGAS is activated, and that this alarm system is turned on,” Ambati said. “This is what leads to the killing of the cells in the retina, and ultimately, vision loss.”

The researchers say that CGAS may be an alarm for harmful problems that warrant responses from the immune system. It may play important roles in conditions such as diabetes, lupus, and obesity, and researchers are working to create drugs that could inhibit its function.

Kerur noted that scientists may be able to develop small molecules that could block cGAS, though it could take several years, and the drug would then need to go through extensive testing to determine its safety and effectiveness for treating macular degeneration. The researchers also hope to develop the means for detecting the levels of the enzyme in patients’ eyes.   Knowing the levels would help doctors determine when it was best to administer a treatment that would block cGAS.

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