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In previous studies from this lab, an alpha7 nACh receptor was found to successfully modulate retinal ganglion cell neuroprotection against glutamate assault when bound to nicotinic acetylcholine receptors, or if an alpha7 nicotinic acetylcholine agonist, such as PNU-282987 was used in in vitro models (Wehrwein et al., 2004; Iwamoto et al., 2013). These in vitro studies support the hypothesis that activation of alpha7 nicotinic ACh receptors triggers neuroprotection against loss of retinal ganglion cells normally induced by excessive glutamate insult. The results from these in vitro studies instigated an in vivo study in our lab using a rat glaucoma model. However, further testing and manipulation of the specific alpha7 nAChR is required to confidently provide evidence concerning ACh receptor’s modulatory capabilities. Therefore in our lab, a variety of acetylcholine agonists that bind to ACh receptors, like PNU-282987 and PHA 568487, will be used to analyze alpha7 nAChR neuroprotection in a rat model of glaucoma. In addition, an acetylcholinesterase inhibitor, Donepezil, will be administered to determine if inhibition of the acetylcholinesterase that normally degrades ACh, elicits a neuroprotective
response normally associated with activation of ACh receptors. Adult Long Evans rats will be used in in vivo glaucoma models, and the survival of retinal ganglion cells will be visualized using a Zeiss confocal microscope with Metamorph software. ANOVA statistical analysis will be performed on retinal ganglion cell survival in glaucoma-induced retinas and compared to control untreated retinas to provide evidence that activation of alpha7 nAChRs prevents loss of retinal ganglion cells in glaucoma. The long-term aim of this study is to find therapeutic preventative treatments against glaucoma and other neurodegenerative diseases.
Kaliszak, Sara, "Neuroprotective effects of Retinal Ganglion cells by specific alpha 7 nicotine acetylcholine receptor agonists and an acetylcholineesterase inhibitor" (2014). Honors Theses. 2592.
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