Eye Center, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, PR China.
Exp Eye Res. 2018 Feb;167:145-151. doi: 10.1016/j.exer.2017.11.001. Epub 2017 Nov 7.
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.
内源性大麻素系统参与了中枢神经系统的神经保护作用。大麻素受体 1（CB1R）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尚不清楚。在这项工作中，我们通过 N-甲基-N-亚硝基脲（MNU）给药建立了光感受器退行性变小鼠模型，以确定大麻素受体的神经保护作用。MNU 诱导的视网膜退行性变与人类色素性视网膜炎（RP）相似。CB1R 拮抗剂 SR141716A 的给药明显恢复了光感受器的丢失，减少了神经胶质反应，并减少了 MNU 诱导的小鼠模型中的异常血管复合物。在 MNU 处理的视网膜中，BC 树突缩小，在膜片钳记录中，ON-BCs 的反应被消除，OFF-BCs 的反应部分减弱。在 MNU+SR1 组中，ON-BCs 的功能和结构均得到恢复。总之，我们的研究表明，CB1R 的抑制可以有效预防 MNU 诱导的视网膜退行性变，提示 CB1R 拮抗剂 SR1 在视网膜退行性变疾病中具有潜在的治疗作用。
