title: Bis(7)-tacrine protects retinal ganglion cells against excitotoxicity via NMDA receptor inhibition.
abstract: OBJECTIVE
  To investigate whether bis(7)-tacrine, a multifunctional drug, inhibits N-methyl-D-aspartate (NMDA) -activated current in retinal ganglion cells(RGC) and provides neuroprotection against retinal cell damage.
  
  
  METHODS
  Purified RGC cultures were obtained from retinas of 1-3 days old Sprague-Dawley(SD) rats, following a two-step immunopanning procedure. After 7 days of cultivation, the inhibition of NMDA-activated current by bis(7)-tacrine was measured by using patch-clamp recording techniques. In animal experiments, RGCs were damaged after intravitreal injection of NMDA (5µL, 40nmol) in adult rats. Bis(7)-tacrine(0.05, 0.1, 0.2mg/kg) or memantine(20mg/kg) was intraperitoneal administered to the rats fifteen minutes before intravitreally injection of NMDA. RGC damage was analyzed by histologic techniques, TUNEL and retrograde labeling techniques.
  
  
  RESULTS
  Whole-cell patch-clamp recordings demonstrated that NMDA (30µmol/L) resulted in approximately -50 pA inward currents that were blocked by bis(7)-tacrine(1µmol/L). Histological examination and retrograde labeling analysis revealed that bis(7)-tacrine induced a significant neuroprotective effect against NMDA-induced cell damage 7 days after NMDA injection. TUNEL staining showed that pretreatment with bis(7)-tacrine was effective in ameliorating NMDA-induced apoptotic cell loss in the retinal ganglion cell layer 18 hours after injection.
  
  
  CONCLUSIONS
  Bis(7)-tacrine possesses remarkable neuroprotective activities against retinal excitotoxicity through inhibition of NMDA receptors.
authors.affiliation: Department of Ophthalmology, the First Hospital of Jingzhou, Yangtze University, Jingzhou 434000, Hubei Province, China.
authors.forename: Zu-Hai
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Liu
authors.forename: Fa-Gang
authors.initials: FG
authors.lastname: Jiang
authors.forename: Xiang
authors.initials: X
authors.lastname: Tian
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Zhu
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Fang