Trigger for most common form of vision loss discovered

A team led by Indian origin researchers in the US has discovered a crucial trigger for macular degeneration, a condition which robs millions of their sight, an advance that may allow doctors to halt the inflammation early on.

"Almost 200 million people in the world have macular degeneration," said Jayakrishna Ambati, from the University of Virginia School of Medicine in the US.

"For the first time, 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," said Ambati.

"This overdrive of inflammation is what ultimately damages cells, and so, potentially, we have a way of interfering very early in the process," he said.
 

Ambati and Nagaraj Kerur, assistant professor at the University of Virginia School of Medicine, along with colleagues have determined that the culprit is an enzyme called cGAS.

The enzyme plays an important role in the body's immune response to infections by detecting foreign DNA.

However, the molecule's newly identified role in the "dry" form of age-related macular degeneration comes as wholly unexpected.

"It is 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," he said.

The researchers noted that cGAS may be an alarm not just for pathogens but for other harmful problems that warrant responses from the immune system.

The enzyme may also play important roles in conditions such as diabetes, lupus and obesity, and researchers already are working to create drugs that could inhibit its function.

"Because the target we are talking about is an enzyme, we could develop small molecules that could block it," Kerur said.

"There are many drugs already on the market that target specific enzymes, such as the statins (which are used to lower cholesterol levels)," he said.