RT Journal Article
A1 Thaler, S.
A1 Schuettauf, F.
A1 Rejdak, R.
A1 Choragiewicz, T. J.
A1 Zarnowski, T.
A1 Zrenner, E.
A1 Wypych, Z.
A1 Knap, N.
A1 Wozniak, M.
A1 Grieb, P.
T1 Neuroprotective Effects of Tempol and Its Acyl Esters in a Rat Partial Optic Nerve Crush Model
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2007
VO 48
IS 13
SP 3286
OP 3286
SN 1552-5783
AB Purpose:To compare the efficacy of Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a superoxide dismutase mimetic, and its 4 acyl derivatives with different numbers of side-chain carbons (Tempol-C4, -C8, -C12, -C16) as retinoprotective agents in a rat model of partial optic nerve crush (PONC). Methods:Tempol in doses of 5.8, 29 and 116 micromole/kg (equivalent to 1, 5 and 20 mg/kg) or its acyl derivatives in doses 5.8 micromole/kg were administered intraperitoneally to Brown-Norway rats 6 hours before the calibrated partial optic nerve crush (PONC) and then once daily for 7 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 PONC. Eyes were enucleated 2 days later, RGC counting was performed on retinal wholemounts. Data are expressed as RGC counts per mm2 of retina +/- SE. Results:In vehicle-treated animals PONC reduced RGC counts by approx. 60%. Tempol significantly attenuated RGC loss after PONC in a dose of 20 mg/kg but not in a dose of 1mg/kg. In molar doses equivalent to 1mg/kg of Tempol, Tempol-C4 and in particular Tempol-C8 showed enhanced neuroprotective effects, similar to that of unmodified Tempol in a dose of 20 mg/kg. Tempol-C12 and C-16 did not produce neuroprotection. Conclusions:Our results indicate that short-chain (C4- and C8-) acyl esters of Tempol are much more potent neuroprotectants than Tempol, however further increase in acyl chain length results in a loss of neuroprotective effects. 
RD 3/5/2021