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Abstract #15262 Published in IGR 8-4
Acetylcholine neuroprotection against glutamate-induced excitotoxicity in adult pig retinal ganglion cells is partially mediated through α4 nAChRs
Thompson SA; Smith O; Linn DM; Linn CLExperimental Eye Research 2006; 83: 1135-1145
In the mammalian retina, excess glutamate release has been shown to be involved in retinal ganglion cell (RGC) death associated with various diseases. Recent studies have determined that activation of α7 nicotinic acetylcholine receptors (nAChRs) partially protect isolated RGCs from glutamate-induced excitotoxicity. In this study, we further classify the types of nAChRs involved in neuroprotection against glutamate-induced excitotoxicity using isolated adult pig RGCs. Cells were isolated with a modified two-step immunoselective panning technique designed to isolate RGCs from other retinal neurons. Once isolated, nAChR subunits were identified using a combination of pharmacological and immunocytochemical techniques. In cell culture experiments, a variety of α4 nAChR specific agonists were found to have a partial neuroprotective against glutamate-induced excitotoxicity. This neuroprotection was abolished in the presence of the α4 nAChR antagonist, dihydro-β-erythroidine (DHβE). Immunocytochemical results localized several nAChR subunits on isolated adult pig RGCs; in particular α4, α7 and β2 nAChR subunits. Large RGCs exclusively immunostained with antibodies against α7 nAChR subunits whereas α4 and β2 subunits exclusively immunostained only small RGCs. Double label experiments provided evidence that α4 and β2 subunits co-localize on small RGCs. Knowledge of the receptor subtypes responsible for neuroprotection may lead to treatments associated with glutamate-induced excitotoxicity.
Dr. S.A. Thompson, Department of Biological Sciences, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008, USA
Classification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
