Role of Oxidative Stress in Retinal Photoreceptor Cell Death in N-Methyl-N-nitrosourea-Treated Mice
Role of Oxidative Stress in Retinal Photoreceptor Cell Death in N-Methyl-N-nitrosourea-Treated Mice
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DOI：
10.1254/jphs.11110fp
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发表时间：
2012-03-01
影响因子：
3.5
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Tsuruma, Kazuhiro;Yamauchi, Mika;Hara, Hideaki
本研究的目的是探讨氧化应激是否有助于视网膜细胞死亡的感光细胞变性的小鼠模型由N-甲基-N-亚硝基脲（MNU）。我们测量了在体外MNU诱导的自由基的产生在视网膜细胞培养的小鼠661 W光感受器衍生的细胞，RGC-5，小鼠神经节细胞系，和原代视网膜细胞。MNU诱导661 W和原代视网膜细胞产生氧化自由基，但在RGC-5细胞中没有。依达拉奉，自由基清除剂，在1 μ M减少MNU诱导的自由基产生661 W和原代视网膜细胞。为了诱导小鼠体内视网膜感光细胞变性，我们通过腹膜内注射给予60 mg/kg MNU。我们在MNU注射后立即和6 h静脉注射1 mg/kg依达拉奉。通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色和氧化应激标记物测量外核层（ONL）的厚度来评价视网膜光感受器变性。MNU给药后7天引起感光细胞损失。依达拉奉抑制ONL变薄，并减少TUNEL阳性细胞和氧化应激标志物。这些结果表明，MNU导致选择性光感受器降解通过氧化应激在体外和体内，可能有助于了解视网膜色素变性的致病机制。
This study aimed to investigate whether oxidative stress contributes to retinal cell death in a mouse model of photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU). We measured in vitro MNU-induced radical production in retinal cell cultures of murine 661W photoreceptor derived cells; RGC-5, a mouse ganglion cell line; and primary retinal cells. The addition of MNU induced oxidative radical generation in 661W and primary retinal cells, but not in RGC-5 cells. Edaravone, a free radical scavenger, at 1 mu M reduced MNU-induced radical production in 661W and primary retinal cells. To induce in vivo retinal photoreceptor degeneration in mice, we administered 60 mg/kg MNU by intraperitoneal injection. We intravenously administered 1 mg/kg edaravone immediately and at 6 h after the MNU injection. Retinal photoreceptor degeneration was evaluated by measuring the thickness of the outer nuclear layer (ONL) by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and by oxidative stress markers. MNU caused photoreceptor cell loss at 7 days after administration. Edaravone inhibited ONL thinning and reduced TUNEL-positive cells and the oxidative stress markers. These findings indicate that MNU leads to selective photoreceptor degradation via oxidative stress in vitro and in vivo and may help to understand the pathogenic mechanism of retinitis pigmentosa.