目的:αB-晶状体蛋白(αBC)属于维持氧稳态所必需的小热休克蛋白家族。本研究旨在探讨αBC对N-甲基-N-亚硝基脲(MNU)诱导的视网膜变性的可能作用及其机制。
方法:将αBC注射到MNU给药小鼠的玻璃体中。通过视网膜电图(ERG)分析实验动物的视网膜形态和视觉功能,谱域光学相干层析成像(SD-OCT)眼底照片,光动力学测试和免疫组织化学测定。
结果:光动力学行为测试和ERG检查表明,通过αBC治疗,MNU给药小鼠的视觉障碍得到了有效改善。OCT分析显示,施用MNU的小鼠的主要视网膜结构被αBC处理有效地拯救。眼底检查表明,通过αBC处理,MNU给药小鼠的病变大小减小。如苏木精和曙红染色所示,通过αBC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-锥光感受器,而不是S锥光感受器,优先获救,表明光感受器群体对αBC具有不同的敏感性。机制研究表明,抗凋亡,αBC的抗氧化和神经营养功能共同促成了这些治疗效果。
结论:玻璃体内递送αBC可以减轻MNU诱导的光感受器变性和视觉障碍。αBC诱导的保护的进一步改进将为色素性视网膜炎提供新的治疗策略。
OBJECTIVE: αB -crystallin (αBC) 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 αBC on N-methyl- N-nitrosourea (MNU) induced retinal degeneration and the underlying mechanisms.
METHODS: The αBC 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 αBC treatment. OCT analysis showed that the major retinal architecture of the MNU administered mice was efficiently rescued by αBC treatment. Fundus examination suggested that the lesion size of the MNU administered mice was decreased by αBC treatment. MNU induced photoreceptor loss was also mitigated by αBC 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 αBC. The mechanism
study suggested that the anti-apoptotic, anti-oxidative and neurotrophic function of αBC collectively contributed to these therapeutic effects.
CONCLUSIONS: Intravitreal delivery of αBC could alleviate MNU induced photoreceptor degeneration and visual impairment. Further refinement of the αBC induced protection would afford a novel therapeutic strategy for retinitis pigmentosa.