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Abstract #20521 Published in IGR 10-1
Neuroprotection of muscarinic receptor agonist pilocarpine against glutamate-induced apoptosis in retinal neurons
Zhou W; Zhu X; Zhu L; Cui YY; Wang H; Qi H; Ren QS; Chen HZCellular and molecular neurobiology 2008; 28: 263-275
Neuroprotection offers potential as an alternative therapy for glaucoma. Pilocarpine, as a typical muscarinic receptor agonist, remains among the major intraocular pressure lowering drugs for the conventional treatment of glaucoma. However, whether pilocarpine also possesses neuroprotection against glutamate cytotoxicity in retinal neurons is still unknown. In rat primary retinal cultures, identification of neuron, cell viability, apoptosis, intracellular Ca2+ concentration, mitochondrial membrane potential, gene expression were studied by immunofluorescence, MTT, High Content Scanning, confocal microscopy, reverse-transcription PCR, and western blot analysis, respectively. Pretreatment of pilocarpine could prevent glutamate-induced neuron death, which was blocked by the non-selective antagonist atropine and the M1-selective muscarinic receptor antagonist pirenzepine. The antiapoptotic effect of pilocarpine was associated with maintaining calcium homeostasis, recovering mitochondrial membrane potential, and regulating the expression of Bcl-2 and Caspase-3. These studies demonstrated that pilocarpine had effective protection against glutamate-induced neuronal apoptosis through M1 muscarinic receptor. The results may provide an insight into the new mechanism of glaucoma therapy that pilocarpine may potentially act as a retinal neuroprotectant.
Dr. H.Z. Chen, Department of Pharmacology, Shanghai Jiao Tong University, School of Medicine, 280 South Chongqing Road, Shanghai 200025, China. yaoli@shsmu.edu.cn
Classification:
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)
11.2 Cholinergic drugs (Part of: 11 Medical treatment)
