The discovery of a crucial trigger for dry macular degeneration (AMD) – an enzyme called cGAS – could lead to the development of a drug to prevent disease progression.

This discovery, at the University of Virginia School of Medicine, was a surprise. Drs. Jayakrishna Ambati and Nagaraj Kerur had determined that cGAS plays an important role in the body's immune response to infections detecting foreign DNA, but its role in dry AMD was unexpected.

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

cGAS may also be an alarm for other problems that warrant responses from the immune system, and may play important roles in conditions like diabetes, lupus and obesity. “Because the target we're talking about is an enzyme, we could develop small molecules that could block it,” said Dr. Kerur. “There are many drugs already on the market that target specific enzymes, such as the statins.”

A drug to inhibit cGAS will take several years to develop. Researchers also hope to find a way to detect enzyme levels in patients' eyes, and determine when best to administer a treatment that blocks cGAS. “This is really precision medicine at the single-molecule level,” said Dr. Ambati.

The findings were published in Nature Medicine.