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M. Fiedorowicz, S. Thaler, R. Rejdak, F. Schuettauf, E. Zrenner, M. Wozniak, P. Grieb; Age-Dependent Neuroprotection of Retinal Ganglion Cells by Tempol C8-acyl Ester in a Rat NMDA Toxicity Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):868.
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Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a superoxide dismutase mimetic, and Tempol acyl esters were shown previously to be neuroprotective on retinal ganglion cells (RGC) in rat partial optic nerve crush (PONC) model. Here, we compare the efficacy of Tempol and its most effective acyl derivative (Tempol-C8) as retinoprotective agents in a rat model of NMDA (N-methyl-D-aspartate) toxicity, using sexually immature and mature animals.
Tempol at doses of 116, 290 and 580 µmol/kg (equivalent to 20, 50 and 100 mg/kg) or Tempol-C8 at doses 2.9, 5.8 and 29 µmol/kg were administered intraperitoneally to male Brown-Norway rats (6 weeks of age, 100-120 g BW and 9-10 weeks of age, 190-210 g BW) 24 hours and 30 minutes before the intravitreous NMDA injection then once daily for 6 consecutive days. Control rats were treated with vehicle (5% ethanol in PBS, pH 7.2). RGC were retrogradely labeled with the fluorescent tracer Fluorogold 5 days after NMDA injection. Eyes were enucleated 2 days later, RGC counting was performed on retinal wholemounts.
In vehicle-treated animals NMDA injection reduced RGC counts by about 90% independently of age. Tempol administration did not affect significantly RGC counts in any group of animals in any dose. In young animals Tempol-C8 showed a neuroprotective effect in a dose-dependent manner with peak activity at a molar dose equivalent to 1 mg/kg of Tempol(increasing RGC counts by approx. 75%). No significant neuroprotection was observed in older animals in doses up to molar doses equivalent to 5 mg/kg of Tempol.
Tempol did not show significant neuroprotective effect on RGC in NMDA toxicity model contrary to its strong protective effect in PONC. Interestingly, Tempol C8-acyl ester is neuroprotective in both PONC and NMDA toxicity models. In NMDA model, however its neuroprotective was only evident in immature rats.
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