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

Abstract

BackgroundGlutamate-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.ResultsIn 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 μM and 0.834 μM, 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.ConclusionsOur 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.

Neuroprotective effect of epigallocatechin‐3‐gallate against N‐methyl‐D‐aspartate‐induced excitotoxicity in the adult rat retina

“…It is a powerful antioxidant exhibiting multifunctional properties, including anti-inflammatory, anti-apoptosis, neuroprotective effect (Sutherland et al 2006;Zhang et al 2007Zhang et al , 2008Peng et al 2008;Xie et al 2010). Recent researches showed that EGCG also reduced the glutamate excitotoxicity, promoted the viability of neuronal cells by inhibiting ionotropic Ca 2+ influx, reduced the excitotoxin-induced malondialdehyde (MDA) production and decreased the reactive oxygen species level in a dose-dependent manner (Lee et al 2004a,b;Fu & Koo 2006;Fang et al 2010;Yu et al 2010). Besides of that, EGCG was found to regulate the glutamate level by an increase in the glutamate uptake of astrocytes, and the activity of excitatory amino acid transporter 2 (EAAT2), the essential protein for the clearance of synaptically released glutamate.…”

Effects of Rhein Lysinate on H2O2-induced cellular senescence of human umbilical vascular endothelial cells

“…• The percentage of normal, early apoptotic, late apoptotic, and necrotic cells were calculated using FACS Calibur and Cell Quest software (Becton-Dickinson, Franklin Lakes, NJ, USA) [15] . …”

In vitro effect of adenosine A2A receptor antagonist SCH 442416 on the expression of glutamine synthetase and glutamate aspartate transporter in rat retinal M�ller cells at elevated hydrostatic pressure

“…Holcombe et al reported that IOP threshold of ~70 mmHg for the maintenance of retinal perfusion and IOPs elevated ≤70 mmHg was consistent with the maintenance of GLAST activity in rat glaucomatous model in vivo (30), which was consistent with our result (40 mmHg pressure). Woldemussie et al found that the expression of GLAST increased and remained high for 2 months, following the elevation of IOP (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) in rat glaucomatous models in vivo, however, the expression of GS showed little change for the first 3 weeks (13). Nonetheless, Zhang et al reported that the induced expression of GS was observed as early as 24 h following the IOP in elevation in the rat models of acute intraocular hypertension (31).…”