title: Neuroprotective effects of bis(7)-tacrine in a rat model of pressure-induced retinal ischemia.
abstract: The retinal ischemia-reperfusion model has been studied extensively and is an ideal animal model for studying clinical situations such as acute glaucoma and optic neuropathy. Our previous reports showed that bis(7)-tacrine had neuroprotective effects against glutamate-induced retinal ganglion cells damage through the drug's anti-NMDA receptor effects. Here, we investigated whether bis(7)-tacrine protects the retina from ischemic injury in a rat model. Retinal ischemia was induced by raising the intraocular pressure to 120 mmHg for 90 min. Rats received intraperitoneal injections of 0.2 mg/kg bis(7)-tacrine or saline at 30 min before ischemia, and then twice a day after retinal ischemia. Morphometric evaluation showed that bis(7)-tacrine dramatically reduced the retinal damage compared with the control group. Moreover, bis(7)-tacrine suppressed ischemia-induced reductions in a- and b-wave amplitudes of electroretinography. Protein levels of p53, the tumor suppressor gene known to induce apoptosis, were increased after ischemic injury, and treatment with bis(7)-tacrine reduced the expression of the protein. Our results suggest that bis(7)-tacrine has a neuroprotective effect against ischemic injury in the rat retina, possibly through the drug's anti-apoptotic effects. Bis(7)-tacrine may potentially be useful as a therapeutic drug in the management of ischemic retinal diseases.
authors.affiliation: Department of Ophthalmology, First Hospital of Jingzhou, Yangtze University, Jingzhou, 434000, Hubei, China.
authors.forename: Jing-bo
authors.initials: JB
authors.lastname: Li
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Zu-hai
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Jia-hua
authors.initials: JH
authors.lastname: Fang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D018696:Neuroprotective Agents; D016159:Tumor Suppressor Protein p53; D013619:Tacrine