Neuroprotective effect of cannabinoid receptor 1 antagonist in the MNU-induced retinal degeneration model
Neuroprotective effect of cannabinoid receptor 1 antagonist in the MNU-induced retinal degeneration model
复制标题
大麻素受体 1 拮抗剂在 MNU 诱导的视网膜变性模型中的神经保护作用
DOI：
10.1016/j.exer.2017.11.001
复制
发表时间：
2018-02-01
影响因子：
3.4
通讯作者：
Shen, Yin
中科院分区：
文献类型：
--
作者：
Chen, Yuanyuan;Luo, Xue;Shen, Yin
内源性大麻素系统对中枢神经系统具有神经保护作用。大麻素受体1（CB 1 R）在小鼠视网膜中广泛表达。然而，大麻素受体在视网膜中的作用仍不清楚。在这项工作中，我们建立了一个感光细胞变性小鼠模型，通过N-甲基-N-亚硝基脲（MNU）管理，以确定大麻素受体的神经保护作用。MNU诱导的视网膜变性的行为类似于人视网膜色素变性（RP）。在MNU诱导的小鼠模型中，CB 1 R拮抗剂SR 141716 A的给药明显恢复了光感受器损失，降低了神经胶质反应性并减少了异常血管复合体。在膜片钳记录中，在MNU处理的视网膜中BC树突收缩，消除了ON-BC反应，部分减少了OFF-BC反应。MNU + SR 1组ON-BCs的功能和结构均得到恢复。综上所述，我们的研究表明，抑制CB 1 R可以有效地防止MNU诱导的视网膜变性，这表明CB 1 R拮抗剂SR 1在视网膜变性疾病中具有潜在的治疗作用。
Endocannabinoid system involves in neuroprotective effects on the central neural system. The cannabinoid receptor 1 (CB1R) is widely expressed in the mouse retina. However, the role of cannabinoid receptors in the retina remains unclear. In this work, we established a photoreceptor degeneration mouse model via N-methyl-N-nitrosourea (MNU) administration to identify the neuroprotective effects of cannabinoid receptors. The MNU-induced retinal degeneration behaves similarly to that in the human retinitis pigmentosa (RP). Administration of the CB1R antagonist SR141716A distinctly recovered the photoreceptor loss, decreased glial reactivity and reduced abnormal vascular complexes in an MNU-induced mouse model. The BC dendrites were shrunk in the MNU-treated retina with eliminated ON-BCs responses and partially diminished OFF-BCs responses in patch clamp recordings. In the MNU + SR1 group, both the function and structure of ON-BCs recovered. Taken together, our study showed that the inhibition of CB1R can effectively prevent MNU-induced retinal degeneration, suggesting a potential therapeutic effect of the CB1R antagonist SR1 in retinal degeneration diseases.