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Abstract #25948 Published in IGR 12-2
Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage
Fang JH; Wang XH; Xu ZR; Jiang FGBMC Neuroscience 2010; 11: 31
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.
J.H. Fang. Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
