Systemic administration of a free radical scavenger, edaravone, protects against light-induced photoreceptor degeneration in the mouse retina
Systemic administration of a free radical scavenger, edaravone, protects against light-induced photoreceptor degeneration in the mouse retina
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DOI：
10.1016/j.ejphar.2010.05.057
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发表时间：
2010-09-10
影响因子：
5
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Imai, Shunsuke;Inokuchi, Yuta;Hara, Hideaki
依达拉奉（3-甲基-1-苯基-2-吡唑啉-5-酮）是一种自由基清除剂，临床上用于治疗急性脑梗死。在这项研究中，我们研究了依达拉奉对光诱导的小鼠视网膜损伤的保护作用。在小鼠暗适应后，通过暴露于8000 lx的白色光3 h诱导小鼠视网膜损伤。通过在光暴露后5天测量外核层厚度并记录视网膜电图（ERG）来评价光感受器损伤。采用TUNEL法检测视网膜细胞损伤，免疫组化和免疫印迹法检测视网膜标本中8-羟基-2-脱氧鸟苷（8-OHdG）的表达和细胞外信号调节蛋白激酶（ERK）、c-Jun N-末端激酶（JNK）和p38等丝裂原活化蛋白激酶（MAPK）的磷酸化。根据外核层厚度的评价，3 mg/kg，i. p.依达拉奉和1 mg/kg。四.在暴露于光后5天，依达拉奉显著保护光诱导的光感受器变性。在ERG测量中，3 mg/kg依达拉奉i. p.在暴露于光后5天抑制视网膜功能障碍。此外，3 mg/kg依达拉奉腹腔注射可降低光暴露后6 h整个视网膜中TUNEL阳性细胞、8-OHdG、磷酸化JNK和磷酸化p38的数量，但不降低磷酸化ERK的数量。这些结果表明，氧化应激在光诱导的视网膜损伤中起关键作用，依达拉奉全身给药可减缓感光细胞变性的进展。(C)2010 Elsevier B. V.保留所有权利。
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. iv. 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. (C) 2010 Elsevier B.V. All rights reserved.