Lev Prasov, M.D., Ph.D., Assistant Professor of Ophthalmology and Visual Sciences and Assistant Professor of Human Genetics, has been awarded a National Institutes of Health (NIH) R01 grant for his work on the role of the retinoic acid-inducible gene I (RIG-I) in glaucoma and viral infection “This project aims to understand how a gene called RIG-I (also called DDX58), which normally helps the body detect and respond to viral infections, could play a role in causing glaucoma,” says Dr. Prasov. “We are especially interested in families where certain changes in this gene are passed down.” RIG-I works like an alarm system for viruses. It finds a special type of genetic material, called double-stranded RNA, which shows up when viruses are present, and then helps the body get rid of the virus. Dr. Prasov and his team have found a change, or mutation, in the RIG-I gene and have shown in the laboratory that this change can make the body’s immune system overreact, even when there isn’t a virus present. This overreaction can lead to a whole-body condition, called Singleton-Merten Syndrome, and can affect the eyes, skin, heart, and joints. “We are trying to understand why patients with a RIG-I gene change get glaucoma and how RIG-I can trigger glaucoma in general,” he says. “We want to know which cells in the eye are involved, how this extra immune response can hurt the part of the eye that drains fluid, and how this can raise the pressure in the eye and cause damage to the optic nerve, the cable that sends visual signals to the brain.” The team also wants to learn why some people in these families have only glaucoma, while others experience health problems in other parts of the body. They are partnering with Pawan Singh, Ph.D., Assistant Professor of Ophthalmology at the University of Missouri School of Medicine, to test whether a viral infection, such as the Zika virus, can trigger or exacerbate these issues. Other collaborations involve Michelle Kahlenberg M.D., Ph.D., Professor of Internal Medicine, Rheumatology and Dermatology at U-M, who is helping Dr. Prasov investigate whether these changes in RIG-I can also lead to other forms of systemic autoimmunity. “We are testing drugs and other treatments to see if they can fix the problems caused by the RIG-I gene changes in animals and cells in the laboratory,” says Dr. Prasov. “We have found that some treatments could block this overactive pathway, and we are testing those treatments in our animal models.” Ultimately, this research could lead to new ways to treat certain types of glaucoma, especially those not caused solely by high pressure in the eye. “We have found a new way that glaucoma could occur, which does not depend only on eye pressure,” he says. “Increasing evidence shows that inflammation driven by the immune system is important in how glaucoma develops.”