TEMPOL, a superoxide dismutase mimic, ameliorates light-induced retinal degeneration.
The efficacy of 4-hydroxy-2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPOL), a metal independent superoxide dismutase (SOD) mimic, in ameliorating light-induced retinal degeneration was investigated. Thirty-six Lewis albino rats were exposed to green fluorescent light (490-580 nm, 160-180 foot-candles) for 24 hr, after dark adaptation for 24 hr. The animals received six intraperitoneal (IP) injections of TEMPOL (100 mg/kg) or an equivalent volume of saline solution (vehicle-treated control groups) at 6 hr intervals starting 6 hr before the light exposure and ending 24 hr after light exposure. Another six rats were used as unexposed controls. The animals were killed at 6 hr, 6 days and 14 days after light exposure. Retinal damage was assessed by light and electron microscopy, measurements of outer nuclear layer (ONL) thickness and rhodopsin levels and counting of macrophages in the subretinal space. After light exposure, the TEMPOL-treated rats showed mild edema of the retinal pigment epithelium (RPE), less densified inner segments (IS) at 6 hr and better preserved photoreceptors at 6 days and 14 days compared with vehicle-treated control groups. Morphometrically the ONL was thicker in the TEMPOL-treated rats than in the vehicle-treated control at 6 days (p<0.01) and 14 days (p<0.05) but no significant difference occurred at 6 hr (p>0.05). Rhodopsin levels in the TEMPOL-treated rats were significantly higher at 6 days (p<0.05) but not at 6 hr (p>0.05) or 14 days (p>0.05). Our results demonstrated that TEMPOL ameliorated light-induced retinal degeneration in rats. These findings are consistent with the hypothesis that superoxide radicals may play a crucial role in mediating light-induced retinal degeneration.
Wang
M
M
Georgiana Dvorak Theobald Ophthalmic Pathology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, USA.
Lam
T T
TT
Fu
J
J
Tso
M O
MO
D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D008027:Light; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects* / Q000648:ultrastructure*; D012162:Retinal Degeneration; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors
D003497:Cyclic N-Oxides; D011500:Protein Synthesis Inhibitors; D013113:Spin Labels; D013482:Superoxide Dismutase; C001803:tempol