神经节细胞层
NADPH氧化酶
标记法
再灌注损伤
免疫印迹
程序性细胞死亡
视网膜
视网膜
内核层
分子生物学
生物
神经保护
视网膜神经节细胞
活性氧
化学
细胞凋亡
缺血
细胞生物学
内科学
医学
生物化学
药理学
神经科学
基因
作者
Harumasa Yokota,S. Priya Narayanan,Wenbo Zhang,Hua Liu,Modesto Rojas,Zhimin Xu,Tahira Lemtalsi,Taiji Nagaoka,Akitoshi Yoshida,Steven E. Brooks,Robert W. Caldwell,Ruth B. Caldwell
摘要
Purpose.: The aim of this study was to determine whether NOX2, one of the homologs of NADPH oxidase, plays a role in neuronal cell death during retinal ischemia. Methods.: Ischemia reperfusion (I/R) injury was generated in C57/BL6 and NOX2−/− mice by increasing the intraocular pressure (IOP) to 110 mm Hg for 40 minutes followed by reperfusion. Quantitative PCR and Western blot analysis were performed to measure NOX2 expression. Reactive oxygen species (ROS) formation was assessed by dihydroethidium imaging of superoxide formation and Western blot analysis for tyrosine nitration. TUNEL assay was performed to determine cell death at 3 days after I/R. Survival of neurons within the ganglion cell layer (GCL) was assessed at 7 days after I/R by confocal morphometric imaging of retinal wholemounts immunostained with NeuN antibody. Activation of mitogen-activated protein kinases and nuclear factor κB (NF-κΒ) was measured by Western blot analysis. Results.: NOX2 mRNA and protein and ROS were significantly increased in wild-type I/R retinas. This effect was associated with a 60% decrease in the number of GCL neurons and a 10-fold increase in TUNEL-positive cells compared with the fellow sham control eyes. Phosphorylation of ERK and NF-κB was significantly increased in wild-type I/R retinas. Each of these effects was markedly attenuated in the NOX2−/− retina (P < 0.01). Conclusions.: These data demonstrate that the deletion of NOX2 can reduce I/R-induced cell death and preserve retinal GCL neurons after I/R injury. The neuronal cell injury caused by I/R is associated with the activation of ERK and NF-κB signaling mechanisms.
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