Rochester wins NIH AMD project

Age-related macular degeneration damages the macula, the part of the eye that handles sharp central vision for reading, driving, and recognizing faces. It is a leading cause of vision loss in older adults. (nei.nih.gov) University of Rochester Medicine said April 27 that Flaum Eye Institute researcher Ruchira Singh won a National Institutes of Health grant to push that work earlier in the disease process. The project aims to find a treatment before later-stage retinal damage is established. (urmc.rochester.edu) Current treatment options are mostly built for advanced disease. Rochester said Food and Drug Administration-approved therapies have limited benefit, can cause side effects, and do not address every stage of age-related macular degeneration. (urmc.rochester.edu) The Rochester team is focusing on secretory phospholipase A2-IIA, or sPLA2-IIA, a protein Singh’s lab identified as a possible early driver of age-related macular degeneration and related macular dystrophies. The lab linked elevated levels of that protein to harmful retinal changes, including drusen, the deposits that mark early disease. (urmc.rochester.edu) Drusen are clumps of lipids and proteins that build up under the retina’s support layer, called the retinal pigment epithelium. In age-related macular degeneration, those deposits are one of the earliest visible signs that the tissue is under stress. (nei.nih.gov 1) (nei.nih.gov 2) Singh’s group got to this target by using patient-derived stem cells, which let researchers grow lab models of retinal tissue from human cells instead of relying only on animal models. Rochester said those models showed a biological signal tied to how the disease starts and progresses. (urmc.rochester.edu) (nei.nih.gov) That grant builds on Rochester’s October 2, 2024 paper in *Developmental Cell*, which identified a related inflammatory pathway in age-related macular degeneration. In that study, the team reported that excess TIMP3 disrupted enzymes needed for eye health and helped drive drusen formation in the model. (urmc.rochester.edu) (nei.nih.gov) The newer project shifts from mapping the pathway to trying to block it. Rochester said the lab is developing a small-molecule therapy designed to eliminate the disease-related protein at lower doses and with fewer off-target side effects than broader drugs. (urmc.rochester.edu) The group has also been testing the biology beyond stem-cell dishes. A 2025 abstract in *Investigative Ophthalmology & Visual Science* reported that mice engineered to overexpress PLA2G2A developed drusen-like deposits, inflammation, retinal pigment epithelium loss, and abnormal blood vessel growth associated with advanced disease. (iovs.arvojournals.org) The bet in Rochester is that treating the trigger earlier could change the course of a disease that often becomes obvious only after retinal damage has started. The next step is turning that protein signal into a therapy that can be tested beyond the lab. (urmc.rochester.edu)