Bis(7)-tacrine protects retinal ganglion cells against excitotoxicity via NMDA receptor inhibition  

作　　者：Zu-Hai Zhang, Jia-Hua Fang 

机构地区：[1]Department of Ophthalmology, the First Hospital of Jingzhou, Yangtze University, Jingzhou 434000, Hubei Province, China [2]Wuhan Institute of Neuroscience & Drug Research, Jianghan University, Wuhan 430056, Hubei Province, China [3]Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China

出　　处：《International Journal of Ophthalmology(English edition)》2011年第2期125-130,共6页国际眼科杂志（英文版）

基　　金：National Natural Science Foundation of China (No.81000380H1204);Natural Science Foundation of Hubei Province,China (No.2008CDA053);Scientific Research Fund of the Ministry of Health,Hubei Province,China (No.QJX2010-53)

摘　　要：AIM: 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 (5 mu L, 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 (30 mu mol/L) resulted in approximately -50 pA inward currents that were blocked by bis (7)-tacrine (1 mu mol/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. CONCLUSION: Bis (7)-tacrine possesses remarkable neuroprotective activities against retinal excitotoxicity through inhibition of NMDA receptors.AIM: 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 (5 mu L, 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 (30 mu mol/L) resulted in approximately -50 pA inward currents that were blocked by bis (7)-tacrine (1 mu mol/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. CONCLUSION: Bis (7)-tacrine possesses remarkable neuroprotective activities against retinal excitotoxicity through inhibition of NMDA receptors.

关 键 词：bis(7)-tacrine N-methyl-D-aspartate receptors EXCITOTOXICITY NEUROPROTECTION 

分 类 号：R774.1[医药卫生—眼科]