Intravitreous Delivery of Ab-Crystallin Ameliorates N-Methyl-N-Nitrosourea Induced Photoreceptor Degeneration in Mice: An in vivo and ex vivo Study
Intravitreous Delivery of Ab-Crystallin Ameliorates N-Methyl-N-Nitrosourea Induced Photoreceptor Degeneration in Mice: An in vivo and ex vivo Study
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玻璃体内注射 Ab-晶状体蛋白可改善 N-甲基-N-亚硝基脲诱导的小鼠光感受器变性：一项体内和离体研究
DOI：
10.1159/000492557
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发表时间：
2018
影响因子：
--
通讯作者：
Teng Dengke
中科院分区：
文献类型：
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作者：
Tao Ye;Ding Lei;Yao Anhui;Yang Zhen;Yang Qinghua;Qin Limin;Yu Linjun;Gao Yanling;Huang Yi Fei;Li Zhengwei;Teng Dengke
背景/目标：α B -晶状体蛋白（α BC）属于维持氧稳态所必需的小的热休克蛋白家族。本研究旨在探讨α BC对N-甲基-N-亚硝基脲（MNU）诱导的视网膜变性的影响及其机制。方法：将α BC注射到MNU给药小鼠的玻璃体中。采用视网膜电图（ERG）、光谱域光学相干断层扫描（SD-OCT）、眼底照相、视动学检测和免疫组织化学方法对实验动物的视网膜形态学和视功能进行分析。结果如下：视动行为测试和ERG检查表明，MNU给药小鼠的视觉障碍被α BC治疗有效地改善。OCT分析显示，施用MNU的小鼠的主要视网膜结构被α BC治疗有效地挽救。眼底检查表明，通过α BC治疗，MNU给药小鼠的病变大小减小。如苏木精和伊红染色所示，α BC处理也减轻了MNU诱导的光感受器损失。特别是，免疫染色研究表明，M-视锥光感受器，而不是S-视锥光感受器，优先获救，表明感光细胞群体具有不同的敏感性α BC。机制研究表明，α BC的抗凋亡、抗氧化和神经营养功能共同促成了这些治疗作用。结论：α BC玻璃体腔注射可减轻MNU诱导的视网膜光感受器变性和视力损害。对α BC诱导的保护作用的进一步改进将为视网膜色素变性提供新的治疗策略。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: alpha B -crystallin (alpha BC) belongs to the family of small heat shock proteins that are necessary for maintaining oxygen homeostasis. This study was designed to explore the possible effects of alpha BC on N-methyl-N-nitrosourea (MNU) induced retinal degeneration and the underlying mechanisms. Methods: The alpha BC was injected into the vitreous bodies of MNU administered mice. The retinal morphology and visual function of experimental animals were analyzed by electroretinography (ERG), Spectral domain optical coherence tomography (SD-OCT), fundus photographs, optokinetic testing and immunohistochemistry assay. Results: Optokinetic behavioural tests and ERG examination suggested that the visual impairments of the MNU administered mice were ameliorated effectively by alpha BC treatment. OCT analysis showed that the major retinal architecture of the MNU administered mice was efficiently rescued by alpha BC treatment. Fundus examination suggested that the lesion size of the MNU administered mice was decreased by alpha BC treatment. MNU induced photoreceptor loss was also mitigated by alpha BC treatment as shown by hematoxylin and eosin staining. In particular, the immunostaining study suggested that M-cone photoreceptors, rather than the S-cone photoreceptors, were preferentially rescued, indicating that the photoreceptor populations have different sensitivities to alpha BC. The mechanism study suggested that the anti-apoptotic, anti-oxidative and neurotrophic function of alpha BC collectively contributed to these therapeutic effects. Conclusion: Intravitreal delivery of alpha BC could alleviate MNU induced photoreceptor degeneration and visual impairment. Further refinement of the alpha BC induced protection would afford a novel therapeutic strategy for retinitis pigmentosa. (C) 2018 The Author(s) Published by S. Karger AG, Basel