Jason Miller, M.D., Ph.D., the James Grosfeld Endowed Professor and Assistant Professor of Ophthalmology and Visual Sciences, has been selected as the 2025 recipient of the prestigious Edward N. and Della L. Thome Memorial Foundation Award for his research in combating age-related macular degeneration. More specifically, Dr. Miller is recognized for his novel work in reducing the toxic fatty deposits that accumulate in the retina’s macula—the part of the eye responsible for sharp, detailed vision. “Macular degeneration causes vision loss because deposits of fat build up around certain cells in the back of the eye, interfering with their ability to detect light,” he says. “The goal of our work is to decrease the buildup of these deposits.” In his work Dr. Miller and his team have explored cells' waste disposal systems, much like a built-in trash compactor, called autophagy. “Typically, scientists have turned on autophagy by manipulating a master regulatory protein called mTOR, but this can disrupt normal cell function,” says Dr. Miller. “We are, therefore, interested in turning on autophagy in a way that does not directly involve mTOR. We want to activate this cellular clean-up system to get rid of the harmful ‘trash-like’ fats that accumulate in macular degeneration.” The project has two components: the first is to find new drug-like molecules that turn on autophagy without harmful side effects; and the second is to test a promising autophagy-promoting molecule called flubendazole that the lab previously discovered to see if it can work not just in a dish of retinal cells but actually in the eye. “This means figuring out creative ways of delivering the flubendazole payload, since flubendazole doesn’t get well-absorbed into the body (and eye) when taken as a pill,” he says. Their work represents the chance to take a potential therapeutic and figure out how to deliver it into animals as a step toward testing it in humans. “Projects like this aim to increase the shots on goal for desperately needed AMD therapies. The more shots on goal you have, the more likely it is that one of them will work,” says Dr. Miller. “Biology is so complicated that we never know what unexpected side effect may arise with a particular drug or therapeutic approach. Our approach with turning on autophagy in macular degeneration represents a distinctly different alternative therapeutic approach compared to the current drugs in clinical trials for macular degeneration, providing a more diversified therapeutic approach to the disease.”