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

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    Abstract:

    AIM: To investigate whether bis(7)-tacrine, a multifun- ctional 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. CONCLUSION: Bis(7)-tacrine possesses remarkable neur- oprotective activities against retinal excitotoxicity through inhibition of NMDA receptors.

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Zu-Hai Zhang, Yu-Wei Liu, Fa-Gang Jiang, et al. Bis(7)-tacrine protects retinal ganglion cells against excitotoxicity via NMDA receptor inhibition. Int J Ophthalmol, 2011,4(2):125-130

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