N -methyl- N -nitrosourea-induced retinal degeneration in mice
N -methyl- N -nitrosourea-induced retinal degeneration in mice
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N-甲基-N-亚硝基脲诱导小鼠视网膜变性
DOI：
10.1016/j.exer.2013.12.019
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发表时间：
2014-04-01
影响因子：
3.4
通讯作者：
Shen, Yin
中科院分区：
文献类型：
--
作者：
Chen, Yuan-Yuan;Liu, Shi-Liang;Shen, Yin
小鼠视网膜变性模型已经研究了很多年，希望了解感光细胞死亡的机制。N -甲基- N -亚硝基脲（MNU）以前已被证明可诱导小鼠视网膜外变性. C57/BL小鼠腹腔注射MNU后，我们观察到外核层（ONL）厚度逐渐减少，与光感受器外节丢失，双极细胞树突退缩和反应性胶质增生相关。GFAP蛋白水平增加证实了反应性胶质增生。在MNU诱导的视网膜变性模型中发现了对中央视网膜的更严重的损伤，而不是周边视网膜。视网膜神经节细胞（RGC）似乎在MNU治疗后至少两个月内幸免。视网膜血管标记后，我们观察到远端血管中的血管复合体，表明视网膜血管损伤。在残余的视网膜感光细胞的MNU处理的小鼠，集中着色核检测电子显微镜，连同线粒体的损失和移位的残余突触带中的感光器。我们还观察到线粒体蛋白质水平降低和光感受器中亚硝基化/硝化量增加。MNU诱导细胞凋亡的机制可能与氧化应激或视网膜血供丧失有关。MNU诱导的小鼠视网膜外层变性是用于光感受器变性疾病如年龄相关性黄斑变性（AMD）和视网膜色素变性（RP）的有用动物模型。(C)2014爱思唯尔有限公司版权所有。
Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). (C) 2014 Elsevier Ltd. All rights reserved.