Characterization of a Cholinergic Synapse in a Model of Glaucoma

Date of Award

4-2018

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. Cindy Linn

Second Advisor

Dr. Wendy Beane

Third Advisor

Dr. David Linn

Fourth Advisor

Dr. Christine Byrd-Jacobs

Keywords

Neuroprotection, glaucoma, rat, acetylcholine, retinal ganglion cell, starburst amacrine cell

Abstract

This research analyzes changes that occur at a retinal cholinergic synapse in a rat glaucoma model. Using this glaucoma model, evidence is presented to suggest a novel neuroprotective role for the release of acetylcholine (ACh) in the adult mammalian retina. Specifically, evidence is presented for changes at the synapse between two groups of neuronal cells within the adult mammalian retina, the starburst amacrine cells (SACs) and the retinal ganglion cells (RGCs). This synapse was analyzed under glaucomatous conditions and after inducing neuroprotection. The studies presented in this thesis will show that ACh released from SACs initiates neuroprotection against insult in RGCs in retinas induced with glaucoma-like conditions using a hypertonic saline injection to the episcleral vein. We believe our studies will demonstrate that cholinergic communication between these two cell types is reduced prior to the loss of RGCs in an in vivo glaucoma model but can be restored with the use of ACh enhancing pharmacological agents. Lastly, we propose a potential cell-survival signaling cascade triggered by an ACh-activated mechanism. These results can provide valuable insight into neuroprotective treatments for diseases involving neuronal cell death such as glaucoma.

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