Cholinergic activity modulates the survival of retinal ganglion cells in culture: the role of M-1 muscarinic receptors

The control of natural cell death is mediated by neurotrophins released by target, afferent and glial cells. In the present work we show that treatmen t of retinal cells 'in vitro' for 48 h with 25 muM carbamylcholine induced a two-fold increase in retinal ganglion cells survival. This effect was dos e-dependent and mediated by M-1 receptors since it could be blocked by 1 mu M telenzepine (a M-1 receptor antagonist) and mimicked by 200 muM oxotremor ine (a M-1 receptor agonist). The effect of carbamylcholine was abolished b y 10 muM BAPTA-AM (an intracellular Ca2+ chelator), 30 muM dantrolene (an i nhibitor of ryanodinic receptors), 500 nM H-89 (an inhibitor of PKA), 1.25 muM chelerythrine chloride (an inhibitor of PKC) and 50 muM PD-98059 (a MEK inhibitor). Treatment with 10 muM genistein (an inhibitor of tyrosine kina se), 25 muM LY-294002 (a PI-3 kinase blocker), 30 nM brefeldin-A (a blocker of polypeptides release), 50 nM K-252a (a Trk receptor inhibitor) and 20 m uM fluorodeoxyuridine (an inhibitor of cell proliferation) totally inhibite d the effect of carbamylcholine. Taken together our results indicate that m uscarinic activity controls the survival of retinal ganglion cells through a mechanism involving the release of polypeptides and activation of Irk rec eptors. (C) 2001 ISDN. Elsevier Science Ltd. All rights reserved.