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John Lelli ACF Abstract FY10

Multiple possible protective mechanisms associated with the alpha7 nAChR in pig retina: Agonist, modulator & feedback mechanisms

Conference Name: Neuroscience 2009

Retinal ganglion cells (RGCs) are responsible for transmitting visual information from the retina to visual centers in the brain. Previous research on RGCs has revealed their vulnerability to glutamate-induced excitotoxicity, a possible glaucomatic mechanism. However, activation of nicotinic acetylcholine receptors (nAChRs) located on RGCs has been shown to provide protection (Wehrwein et al., 2004). Previous results (Bader & Linn, 2007) showed that PNU-282987 displayed significant neuroprotective effects against glutamate toxicity. The α7-specific nicotinic antagonist, methyllycaconitine (MLA), blocked this neuroprotective effect at 100nM indicating a direct agonist action. We found further protective effects of α7 (nAChR) activation by applying a modulator with the agonist to RGCs. The selective allosteric modulator, PNU-120596, enhanced the protective action of the agonist in a dose-dependent manner with maximal effects exceeding survival seen under control conditions. Agonist and modulator, in the absence of glutamate, showed increase in cell survival. This suggests that the modulator provides protection against other causes of cell loss. In addition, evidence exists that α7 receptors may exist on the cholinergic amacrine cells themselves. Tropisetron was found to evoke labeled ACh release comparable to kainate with having a more potent and prolonged effect of increased basal release. These data suggest direct and indirect activation of neuroprotective mechanisms in RGCs.

Lead presenter: John Lelli.  Other presenters: David Linn

(Other names appearing on the poster but did not attend the conference were Kim Wisniewski & Viralkumar Patel)