Figure 6

The neuroprotective effect of galantamine in glaucoma is mediated by activation of ACh muscarinic receptors. (a) Co-injection of galantamine with scopolamine, an inhibitor of all mAChR types, abrogated the prosurvival effect of galantamine. In contrast, the α7 nAChR antagonist methyllycaconitine (MLA), the α4β2 nAChR antagonist dihydro-β-erythroidine (DHβ-E) or the antagonist of all nAChR mecamylamine (MMA) did not reduce galantamine-induced survival of axotomized RGCs (ANOVA, ^*P<0.001). (b) Co-administration of galantamine and scopolamine (SCO) completely inhibited galantamine-induced RGC neuroprotection in glaucomatous eyes at 5 weeks after OHT (ANOVA, ^*P<0.001). Administration of MLA, DHβ-E, MMA or SCO, by themselves, did not cause RGC death or adverse effects in non-injured retinas (c), nor did they promote survival in injured rat retinas (d) (n=3–6/group). (e) Injection of galantamine in combination with the M1 mAChR blocker pirenzepine (PRZ), the M2 mAChR antagonist DX116, the M3 mAChR blocker 4-DAMP or the M4 mAChR antagonist tropicamide (TRO), showed that galantamine-induced neuroprotection is mediated through activation of M1 and M4 mAChR (ANOVA, ^*P<0.001)