Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage.

Jia Hua Fang, Xing Hua Wang, Zhi Rong Xu, Fa Gang Jiang

Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

BMC neuroscience 2010

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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. 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. 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.

Citation

Jia Hua Fang, Xing Hua Wang, Zhi Rong Xu, Fa Gang Jiang. Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage. BMC neuroscience. 2010;11:31