Novel Tools to Identify and Target Astrocytic Subtypes to Treat Glaucoma

Vision loss in glaucoma results from damage to the retinal ganglion cells (RGCs), which are the neurons that connect the eye to the brain. RGC axons from throughout the retina converge at the optic nerve head to exit the eye. A critical insult to RGC axons occurs at the optic nerve head, where they interact extensively with another resident cell type, astrocytes. Astrocytes are thought to play both neuroprotective and neurotoxic roles in complex neurodegenerative diseases, such as glaucoma and Alzheimer's. Our studies will provide important molecular information and tools for manipulating optic nerve head astrocytes to understand and treat glaucoma. We will use cutting edge single-nuclear RNA sequencing technology to dissect out the molecular pathways that define neurotoxic versus neuroprotective astrocytes in optic nerve heads of glaucoma and normal mouse eyes. We will also develop new viral tools for selectively manipulating genes in optic nerve head astrocytes that can be used for gene therapy approaches by the glaucoma research community. These studies will pave the path for the development of a new avenue of glaucoma therapies directed towards optic nerve head astrocytes.