Akiyama Goichi, Azuchi Yuriko, Guo Xiaoli, Noro Takahiko, Kimura Atsuko, Harada Chikako, Namekata Kazuhiko, Harada Takayuki
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4908-4914. doi: 10.1167/iovs.17-22250.
To assess the therapeutic potential of edaravone, a free radical scavenger that is used for the treatment of acute brain infarction and amyotrophic lateral sclerosis, in a mouse model of optic nerve injury (ONI).
Two microliters of edaravone (7.2 mM) or vehicle were injected intraocularly 3 minutes after ONI. Optical coherence tomography, retrograde labeling of retinal ganglion cells (RGCs), histopathology, and immunohistochemical analyses of phosphorylated apoptosis signal-regulating kinase-1 (ASK1) and p38 mitogen-activated protein kinase (MAPK) in the retina were performed after ONI. Reactive oxygen species (ROS) levels were assessed with a CellROX Green Reagent.
Edaravone ameliorated ONI-induced ROS production, RGC death, and inner retinal degeneration. Also, activation of the ASK1-p38 MAPK pathway that induces RGC death following ONI was suppressed with edaravone treatment.
The results of this study suggest that intraocular administration of edaravone may be a useful treatment for posttraumatic complications.
在视神经损伤（ONI）小鼠模型中评估依达拉奉（一种用于治疗急性脑梗死和肌萎缩侧索硬化的自由基清除剂）的治疗潜力。
ONI后3分钟，将2微升依达拉奉（7.2 mM）或赋形剂眼内注射。ONI后进行光学相干断层扫描、视网膜神经节细胞（RGCs）逆行标记、组织病理学以及视网膜中磷酸化凋亡信号调节激酶-1（ASK1）和p38丝裂原活化蛋白激酶（MAPK）的免疫组织化学分析。用CellROX Green试剂评估活性氧（ROS）水平。
依达拉奉改善了ONI诱导的ROS产生、RGC死亡和视网膜内层变性。此外，依达拉奉治疗抑制了ONI后诱导RGC死亡的ASK1-p38 MAPK通路的激活。
本研究结果表明，眼内给予依达拉奉可能是治疗创伤后并发症的一种有效方法。
