Date of Award

6-2013

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Cindy L. Linn

Second Advisor

Dr. Christine Byrd-Jacobs

Third Advisor

Dr. John J. Jellies

Keywords

glaucoma, neuroprotection, excitotoxicity, Alpha7 agonists, PNU-282987

Access Setting

Masters Thesis-Open Access

Abstract

Acetylcholine (ACh) has been shown to have a neuroprotective effect against glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs) through activation of α7 nicotinic ACh receptors (nAChRs). In this study, the neuroprotective effects of the α7 nAChR agonist, PNU-282987, were investigated using an in vivo model of glaucoma in adult Long Evans rats. Hypertonic saline injections were used to induce a glaucoma model. After one month, retinas were removed, flat mounted, fixed and labeled with an antibody against Thy 1.1 to label RGCs and fluorescently tagged for visualization. Eye drop application of PNU-282987 resulted in neuroprotection against RGC loss in a dose-dependent manner compared to untreated controls when applied 3 days before hypertonic injections and for 30 days following the procedure. Liquid chromatography with mass spectroscopy with quad capabilities (LC/MSMS) demonstrated that PNU-282987 can be detected in the retina with small amounts in blood plasma and no detectable levels in heart samples. These results support the hypothesis that eye drop application of the α7 nAChR agonist, PNU-282987, can prevent loss of RGCs associated under glaucoma-like conditions. Copyright byCopyright by Copyright byCopyright by Copyright byCopyright by Copyright by David Mata David Mata 201

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