Research Day
RETINAL GANGLION CELL AND AXON REGENERATION IN ADULT MURINE GLAUCOMA
Document Type
Abstract
Date
2021
Abstract
Glaucoma is a neurodegenerative disease of the retina, causing loss of the retinal ganglion cells (RGCs) and ultimately vision. We previously demonstrated that an α7 nicotinic acetylcholine receptor agonist, PNU-282987 (PNU), works as a neurogenic compound in adult mammalian retinas. We hypothesized that PNU stimulates regeneration to restore lost RGCs in an induced model of glaucoma in adult mice and that newly regenerated RGCs send axons down the optic nerve. Glaucoma-like damage was induced in adult mice by injecting 1.2M hypertonic saline into the episcleral venous plexus. This injection causes scar tissue that reduces aqueous humor outflow in the trabecular meshwork, leading to an increase in intraocular pressure, a significant loss of RGCs, and de-fasciculation of their axon bundles. Glaucomatous retinas were treated with 100 mMPNU and/or BrdU over a timeline of several days. To identify regenerated RGCs, cells were double labeled with Thy1.2 and BrdU. New cells were prevalent after just 3 days of PNU treatment. Like other models of regeneration, we determined that the source of new RGCs were from the resident Müller glia. Also, we observed axonal reorganization after PNU treatment. To test the hypothesis that new RGCs axons would converge in the optic nerve, we used a transgenic mouse line for lineage tracing studies. Our findings support the hypothesis that PNU treatment causes regeneration of lost RGCs following glaucomatous-like damage and project axons into the optic nerve. Further work is currently underway to determine if these new RGCs can restore vision.