Date of Defense

12-7-2016

Date of Graduation

12-2016

Department

Biological Sciences

First Advisor

Cindy Linn

Second Advisor

Douglas Coulter

Third Advisor

Cynthia Gossman

Abstract

Recent discoveries from this lab have demonstrated that activation of alpha7 nicotinic acetylcholine receptors (α7 nAChRs) on retinal ganglion cells (RGCs) in the retina is linked to neuroprotection of RGCs that are typically lost in glaucoma-like conditions. Various chemical agents have been produced to increase overall neurotransmission of ACh from cholinergic neurons. DMP-543 is an agent that increases calcium release from cholinergic synaptic terminals. Donepezil is an acetylcholinesterase inhibitor that inhibits the breakdown of ACh in the synaptic cleft, prolonging ACh’s effect. In this study, the neuroprotective activity of these two agents was analyzed at the synapse between starburst amacrine cells and RGCs in adult Long Evans rats to determine if these agents can prevent the loss of RGCs associated with glaucoma. Glaucoma-like conditions were induced in-vivo via hypertonic saline injection into the episcleral vein of adult Long Evans rat eyes. Experiments were designed to induce glaucoma in both eyes of adult Long Evans rats. The right eye was also treated with eye drops containing various concentrations of DMP-543 or Donepezil while the left eye was untouched to serve as the internal control. RGC survival in a flat-mounted retina was quantified after immunostaining with an antibody against Thy 1.1 using a Nikon confocal microscope and ImageJ software. Neuroprotection against RGC loss occurred if 10 μM DMP-543 was applied to adult rat eyes and may also occur with the use of 100 μM DMP-543 and 10 μM Donepezil. Results supported the hypothesis that eye drop application of these agents can prevent glaucoma associated RGC loss in the mammalian retina and may have greater implications regarding other diseases involving ACh deficits and α7 nAChRs.

Access Setting

Honors Thesis-Open Access

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