Systemic administration of a free radical scavenger, edaravone, protects against light-induced photoreceptor degeneration in the mouse retina.
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of acute cerebral infarction. In this study, we investigated the protective effects of edaravone against light-induced retinal damage in the mouse. Retinal damage in the mouse was induced by exposure to white light at 8000lx for 3h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5days after the light exposure and recording the electroretinogram (ERG). Retinal cell damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the expression of 8-hydroxy-2-deoxyguanosine (8-OHdG) and the phosphorylation of mitogen-activated protein kinases (MAPKs) such as extracellular signal regulated protein kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 were analyzed in the retinal samples by immunohistochemistry and immunoblotting. According to evaluation of outer nuclear layer thickness, 3mg/kg, i.p. of edaravone and 1mg/kg. i.v. of edaravone significantly protected against light-induced photoreceptor degeneration at 5days after exposure to light. In ERG measurement, 3mg/kg, i.p. of edaravone inhibited retinal dysfunction at 5days after exposure to light. In addition, 3mg/kg, i.p. of edaravone decreased the numbers of TUNEL-positive cells, 8-OHdG, phosphorylated JNK, and phosphorylated p38, but not that of phosphorylated ERK, in the whole retina at 6h after light exposure. These findings suggest that oxidative stress plays a pivotal role in light-induced retinal damage and that systemic administration of edaravone may slow the progression of photoreceptor degeneration.
Imai
Shunsuke
S
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Inokuchi
Yuta
Y
Nakamura
Shinsuke
S
Tsuruma
Kazuhiro
K
Shimazawa
Masamitsu
M
Hara
Hideaki
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D000077553:Edaravone; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000528:radiation effects; D004596:Electroretinography; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*
D016166:Free Radical Scavengers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D020928:Mitogen-Activated Protein Kinases; D003849:Deoxyguanosine; D000077553:Edaravone; D000983:Antipyrine