Department of Anesthesiology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai 317000, China; Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; College of Nursing, Wenzhou Medical University, Wenzhou 325035, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Department of Anesthesiology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai 317000, China.
Biochem Biophys Res Commun. 2024 Jul 30;719:150048. doi: 10.1016/j.bbrc.2024.150048. Epub 2024 May 11.
Double knockout of miR-183 and miR-96 results in retinal degeneration in mice; however, single knockout of miR-96 leads to developmental delay but not substantial retinal degeneration. To further explore the role of miR-96, we overexpressed this miRNA in mouse retinas. Interestingly, we found that overexpression of miR-96 at a safe dose results in retinal degeneration in the mouse retina. The retinal photoreceptors dramatically degenerated in the miR-96-overexpressing group, as shown by OCT, ERG and cryosectioning at one month after subretinal injection. Degenerative features such as TUNEL signals and reactive gliosis were observed in the miR-96-overexpressing retina. RNA-seq data revealed that immune responses and microglial activation occurred in the degenerating retina. Further qRT‒PCR and immunostaining experiments verified the microglial activation. Moreover, the number of microglia in the miR-96-overexpressing retinas was significantly increased. Our findings demonstrate that appropriate miR-96 expression is required for mouse retinal homeostasis.
双重敲除 miR-183 和 miR-96 会导致小鼠视网膜变性；然而，miR-96 的单一敲除会导致发育迟缓，但不会导致明显的视网膜变性。为了进一步探讨 miR-96 的作用，我们在小鼠视网膜中过表达了这种 miRNA。有趣的是，我们发现，miR-96 的安全剂量过表达会导致小鼠视网膜变性。在视网膜下注射一个月后，通过 OCT、ERG 和冷冻切片，发现 miR-96 过表达组的视网膜光感受器明显退化。在 miR-96 过表达的视网膜中观察到 TUNEL 信号和反应性神经胶质增生等退行性特征。RNA-seq 数据显示，在变性的视网膜中发生了免疫反应和小胶质细胞激活。进一步的 qRT-PCR 和免疫染色实验证实了小胶质细胞的激活。此外，miR-96 过表达的视网膜中的小胶质细胞数量明显增加。我们的研究结果表明，适当的 miR-96 表达对于小鼠视网膜的稳态是必需的。
