Date of Defense

12-5-2013

Date of Graduation

12-2013

Department

Biological Sciences

First Advisor

Cindy Linn

Second Advisor

Sherine Obare

Third Advisor

Gellert Mezei

Abstract

PURPOSE: This study was designed to investigate the neuroprotective effects of a specific nicotinic ACh agonist, PNU-282987, on the loss of retinal ganglion cells (RGCs) in a rat glaucoma model. A time-dependent study using 2 mM PNU-282987 was performed to determine the neuroprotective effect in the vertebrate retina.

METHODS: Hypertonic saline solution (2M NaCl) was injected into the episcleral vein of the rat’s eye to reduce the numbers of RGCs and mimic the effect of glaucoma. In one set of studies, PNU-282987 was applied to the right eye of each experimental animal as eye drops in combination with the NaCl saline injections to determine if activation of nicotinic ACh receptors has a neuroprotective effect in the vertebrate retina. In addition, PNU-282987 was tested by itself without the hypertonic saline injection surgery, to investigate the physiological effect on the RGCs.

RESULTS: The results from this study provided evidence that short-term treatment with PNU-282987 before NaCl injection, provided neuroprotection against the loss of RGCs that is normally associated with the procedure. Longer-term treatment resulted in a proliferation of RGCs compared to their internal controls by an average of 28.97%. In addition, when PNU-282987 was applied by itself without the NaCl injection to induce glaucoma-like conditions, it caused a short-term decrease of RGCs, which was followed by proliferation of RGCs. Four weeks of PNU 282987 treatment induced an increase of RGCs by an average of 30.7%.

CONCLUSION: 2 mM PNU-282987 has direct effect on RGCs and was shown to prevent the loss of RGCs normally associated with glaucoma-like conditions. It is possible that PNU-282987 could be developed in the future as a treatment for the loss of RGCs that are associated with a number of retinal diseases.

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Honors Thesis-Open Access

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