title: Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage.
abstract: BACKGROUND
  Glutamate-mediated excitotoxicity, primarily through N-methyl-D-aspartate (NMDA) receptors, may be an important cause of retinal ganglion cells (RGCs) death in glaucoma and several other retinal diseases. Bis(7)-tacrine is a noncompetitive NMDA receptors antagonist that can prevent glutamate-induced hippocampal neurons damage. We tested the effects of bis(7)-tacrine against glutamate-induced rat RGCs damage in vitro and in vivo.
  
  
  RESULTS
  In cultured neonatal rats RGCs, the MTT assay showed that glutamate induced a concentration- and time-dependent toxicity. Bis(7)-tacrine and memantine prevented glutamate-induced cell death in a concentration-dependent manner with IC50 values of 0.028 microM and 0.834 microM, respectively. The anti-apoptosis effects of bis(7)-tacrine were confirmed by annexin V-FITC/PI staining. In vivo, TUNEL analysis and retrograde labeling analysis found that pretreatment with bis(7)-tacrine(0.2 mg/kg) induced a significant neuroprotective effect against glutamate-induced RGCs damage.
  
  
  CONCLUSIONS
  Our results showed that bis(7)-tacrine had neuroprotective effects against glutamate-induced RGCs damage in vitro and in vivo, possibly through the drug's anti-NMDA receptor effects. These findings make bis(7)-tacrine potentially useful for treating a variety of ischemic or traumatic retinopathies inclusive of glaucoma.
authors.affiliation: Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Jia Hua
authors.initials: JH
authors.lastname: Fang
authors.forename: Xing Hua
authors.initials: XH
authors.lastname: Wang
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Xu
authors.forename: Fa Gang
authors.initials: FG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D013619:Tacrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D013619:Tacrine; D008559:Memantine