Authors: Himani Gubbi, Casey Keuthan, Lei Xu , John Ash
Faculty Mentor: John Ash
College: College of Medicine
The retina is a complex tissue that houses photoreceptors crucial to the visual process. It is hypothesized that disruptions to the metabolism of the retina can cause photoreceptor degeneration. Previous literature has shown the importance of AMPK as an important regulator of cell metabolism in different cell types. We have previously shown that metformin, an activator of AMPK, can protect photoreceptors in models of retinal degeneration; however, the mechanism of this protection is unclear. This project further characterizes metformin in the protection of photoreceptors from light damage and investigates the neuroprotective role of two downstream metabolic regulators of AMPK, PGC1-α and PGC1-βthrough genetic knockout studies. For the metformin studies, BalbC mice were treated with metformin for one week before being exposed to damaging light for various time intervals after the last day of treatment. Optical coherence tomography (OCT) was performed to monitor retinal morphology after light damage. Retinal structure and function were also assessed in retinal-specific PGC-1 knockout mice in normal and light damage conditions. Together, this work provides more insight into the important metabolic processes of the retina and AMPK-mediated protection from retinal degeneration.