Date of Award

6-2021

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Cindy Linn

Second Advisor

Dr. Wendy Beane

Third Advisor

Dr. Pamela Hoppe

Keywords

Retina, glaucoma, regeneration, neurogenesis, DBA/2J Mice

Access Setting

Masters Thesis-Open Access

Abstract

Glaucoma is a degenerative retinal disease characterized by progressive loss of retinal ganglion cells (RGCs). Previous studies have shown that application of a specific α7 nicotinic acetylcholine receptor agonist, PNU-282987 (PNU), onto the murine retina induces neurogenesis of numerous retinal cell types, including RGCs. The aim of this study is to characterize the short-term and long-term effects of PNU in a glaucoma model. The effects of PNU were analyzed in a DBA/2J mouse model that auto-induces a glaucoma-like condition in adulthood. These mice manifest an elevated intraocular pressure (IOP) starting at 6 months, followed by loss of RGCs. To assess short-term regenerative effects, PNU treatment was applied daily as eye drops for 2 weeks to DBA/2J mice at various ages (3, 6, and 10 months). To assess the effects of early treatment, a chronic early treatment group began receiving PNU at either 3 or 6 months and received weekly treatment until the animals reached 10 months. An acute early treatment group received two-week daily treatment at either 3 or 6 months, then no further treatment until they reached 10 months. Following treatment, retinas were removed, fixed, processed using IHC procedures, and RGC regeneration was assessed and compared. Results showed a 29% loss of RGCs by 10 months of age in this DBA/2J colony. Two-week application of PNU induced a significant 21% increase in RGCs across all time points. Chronic early treatment produced a similarly significant increase in RGCs while acute early treatment had no effect on RGC numbers. 2-week treatment with PNU, as well as chronic long-term treatment, induced a significant increase in the number of RGCs in the DBA/2J retina, counteracting the effects of the DBA/2J genetic glaucoma-like condition. These results suggest the future clinical potential of PNU in the treatment of degenerative retinal diseases.

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