Department of Biological Structure, University of Washington, Health Sciences Center, Box 357420, 1959 Pacific Street NE, Seattle, WA, 98195, USA.
Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, 37232, USA.
Nat Commun. 2017 Nov 17;8(1):1603. doi: 10.1038/s41467-017-01624-y.
To better understand the roles of microRNAs in glial function, we used a conditional deletion of Dicer1 (Dicer-CKO) in retinal Müller glia (MG). Dicer1 deletion from the MG leads to an abnormal migration of the cells as early as 1 month after the deletion. By 6 months after Dicer1 deletion, the MG form large aggregations and severely disrupt normal retinal architecture and function. The most highly upregulated gene in the Dicer-CKO MG is the proteoglycan Brevican (Bcan) and overexpression of Bcan results in similar aggregations of the MG in wild-type retina. One potential microRNA that regulates Bcan is miR-9, and overexpression of miR-9 can partly rescue the effects of Dicer1 deletion on the MG phenotype. We also find that MG from retinitis pigmentosa patients display an increase in Brevican immunoreactivity at sites of MG aggregation, linking the retinal remodeling that occurs in chronic disease with microRNAs.
为了更好地了解 microRNAs 在神经胶质功能中的作用，我们在视网膜 Müller 胶质细胞（MG）中使用 Dicer1 的条件性缺失（Dicer-CKO）。MG 中的 Dicer1 缺失早在缺失后 1 个月就导致细胞异常迁移。在 Dicer1 缺失后 6 个月，MG 形成大的聚集物，严重破坏了正常的视网膜结构和功能。在 Dicer-CKO MG 中上调最明显的基因是蛋白聚糖 Brevican（Bcan），Bcan 的过表达导致野生型视网膜中 MG 的类似聚集。一种可能调节 Bcan 的 microRNA 是 miR-9，miR-9 的过表达可以部分挽救 Dicer1 缺失对 MG 表型的影响。我们还发现，来自色素性视网膜炎患者的 MG 在 MG 聚集部位显示出 Brevican 免疫反应性增加，将慢性疾病中发生的视网膜重塑与 microRNAs 联系起来。
