October 24, 2024 | 3-4.30 p.m. | HNO Lecture Hall

Retinal ganglion cells (RGCs) degenerate in irreversible blinding disease like glaucoma and optic neuropathy. To be understand the pathology of RGCs that leads to cell death, we have developed in vivo biosensor imaging to track cellular traits and dynamics in individual RGCs over the course of degeneration induced by axon damage. Measuring Ca 2+ levels chronically in RGCs, we observed that well-surviving RGCs tend to have higher baseline Ca2+ levels, and maintain these higher levels during the degenerative time course. To begin dissecting the mechanisms that link intracellular Ca 2+ to survival, we are beginning to examine specific Ca 2+ subdomains within RGCs. Doing so, we have observed that mitochondrial Ca2+ levels are also a feature more common in well-surviving RGCs, and that elevating mitochondrial Ca2+ with AAV2 based gene therapy mildly protects RGCs from degeneration. We are currently performing experiments to determine how mitochondrial Ca2+ may protect RGCs from degeneration with a focus on cellular metabolism and energetics.

Dr Philip Williams is an Assistant Professor, Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine