Systemic administration of a free radical scavenger, edaravone, protects against light-induced photoreceptor degeneration in the mouse retina

Abstract

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 8000 lx for 3 h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5 days 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, 3 mg/kg, i.p. of edaravone and 1 mg/kg. i.v. of edaravone significantly protected against light-induced photoreceptor degeneration at 5 days after exposure to light. In ERG measurement, 3 mg/kg, i.p. of edaravone inhibited retinal dysfunction at 5 days after exposure to light. In addition, 3 mg/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 6 h 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.