{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:03:15Z","timestamp":1790128995243,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,11,27]],"date-time":"2013-11-27T00:00:00Z","timestamp":1385510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Muscarinic acetylcholine receptor agonist pilocarpine reduces intraocular pressure (<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>) of glaucoma mainly by stimulating ciliary muscle contraction and then increasing aqueous outflow. It is of our great interest to know whether pilocarpine has the additional properties of retinal neuroprotection independent of <jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content> lowering <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In rat primary retinal cultures, cell viability was measured using an <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content> assay and the trypan blue exclusion method, respectively. Retinal ganglion cells (<jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s) were identified by immunofluorescence and quantified by flow cytometry. For the <jats:italic>in vivo<\/jats:italic> study, the retinal damage after retinal ischemia\/reperfusion injury in rats was evaluated by histopathological study using hematoxylin and eosin staining, transmission electron microscopy, and immunohistochemical study on cleaved caspase\u20103, caspase\u20103, and Ch<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pretreatment of pilocarpine attenuated glutamate\u2010induced neurotoxicity of primary retinal neurons in a dose\u2010dependent manner. Protection of pilocarpine in both retinal neurons and <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s was largely abolished by the nonselective muscarinic receptor antagonist atropine and the M1\u2010selective muscarinic receptor antagonist pirenzepine. After ischemia\/reperfusion injury in retina, the inner retinal degeneration occurred including ganglion cell layer thinning and neuron lost, and the optic nerve underwent vacuolar changes. These degenerative changes were significantly lessened by topical application of 2% pilocarpine. In addition, the protective effect of pilocarpine on the ischemic rat retina was favorably reflected by downregulating the expression of activated apoptosis marker cleaved caspase\u20103 and caspase\u20103 and upregulating the expression of cholinergic cell marker Ch<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, this highlights pilocarpine through the activation of muscarinic receptors appear to afford significant protection against retinal neurons damage and optic nerve degeneration at clinically relevant concentrations. These data also further support muscarinic receptors as potential therapeutic neuroprotective targets in glaucoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12187","type":"journal-article","created":{"date-parts":[[2013,11,27]],"date-time":"2013-11-27T12:19:33Z","timestamp":1385554773000},"page":"227-236","source":"Crossref","is-referenced-by-count":27,"title":["Activation of Muscarinic Receptors Protects against Retinal Neurons Damage and Optic Nerve Degeneration <i>In Vitro<\/i> and <i>In Vivo<\/i> Models"],"prefix":"10.1111","volume":"20","author":[{"given":"Pan\u2010Pan","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Pharmacology Institute of Medical Sciences Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Hong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shanghai Institute of Health Sciences Shanghai 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