Protection of retinal pigment epithelium by OT-551 and its metabolite TEMPOL-H against light-induced damage in rats.
OT-551 (1-hydroxy-4-cyclopropanecarbonyloxy-2,2,6,6-tetramethylpiperidine hydrochloride), is a novel small molecule with antioxidant and anti-inflammatory effects. Protective efficacy of OT-551 and its metabolite TEMPOL-H (TP-H) against light-induced degeneration of retinal pigment epithelium (RPE) was tested. Albino rats were intraperitoneally injected with OT-551, TP-H, or water approximately 30 min prior to a 6 h exposure to 2700 lux white fluorescent light. Retinal protection was evaluated histologically by counting the RPE cell nuclei and measuring the extent of RPE damage on the retinal sections as RPE damage index (%). Following light exposure, the number of RPE cell nuclei was significantly reduced in light-exposed eyes from water-treated animals, while the number was not significantly different between light-exposed and unexposed eyes from the animals treated with 100 mg/kg TP-H or with any dose of OT-551 in the inferior hemisphere, and with 100 mg/kg OT-551 in the superior hemisphere. RPE damage index was significantly lower in the animals treated with any dose of OT-551 compared to water-treated animals both in the inferior and superior hemispheres. Systemic administration of OT-551 and TP-H provides RPE cell protection against acute light damage, and the protection by OT-551 was greater than by TP-H.
Tanito
Masaki
M
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States. tanito-oph@umin.ac.jp
Li
Feng
F
Anderson
Robert E
RE
D000818:Animals; D002452:Cell Count; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D019811:Hydroxylamine / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008027:Light; D010880:Piperidines / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*
D003497:Cyclic N-Oxides; C550190:OT-551; D010880:Piperidines; D011837:Radiation-Protective Agents; D019811:Hydroxylamine; C505333:TEMPOL-H