Kang Seoyoung, Larbi Daniel, Andrade Monica, Reardon Sara, Reh Thomas A, Wohl Stefanie G
Department of Biological and Vision Sciences, College of Optometry, The State University of New York, New York, NY, United States.
Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA, United States.
Front Cell Dev Biol. 2021 Jan 26;8:620459. doi: 10.3389/fcell.2020.620459. eCollection 2020.
Müller glia (MG) are the predominant glia in the neural retina and become reactive after injury or in disease. microRNAs (miRNAs) are translational repressors that regulate a variety of processes during development and are required for MG function. However, no data is available about the MG miRNAs in reactive gliosis. Therefore, in this study, we aimed to profile miRNAs and mRNAs in reactive MG 7 days after light damage. Light damage was performed for 8 h at 10,000 lux; this leads to rapid neuronal loss and strong MG reactivity. miRNAs were profiled using the Nanostring platform, gene expression analysis was conducted via microarray. We compared the light damage dataset with the dataset of Dicer deleted MG in order to find similarities and differences. We found: (1) The vast majority of MG miRNAs declined in reactive MG 7 days after light damage. (2) Only four miRNAs increased after light damage, which included miR-124. (3) The top 10 genes found upregulated in reactive MG after light damage include and . (4) The miRNA decrease in reactive MG 7 days after injury resembles the profile of Dicer-depleted MG after one month. (5) The comparison of both mRNA expression datasets (light damage and Dicer-cKO) showed 1,502 genes were expressed under both conditions, with , , and as top upregulated candidates. (6) The DIANA-TarBase v.8 miRNA:RNA interaction tool showed that three miRNAs were found to be present in all networks, i.e., after light damage, and in the combined data set; these were miR-125b-5p, let-7b and let-7c. Taken together, results show there is an overlap of gene regulatory events that occur in reactive MG after light damage (direct damage of neurons) and miRNA-depleted MG (Dicer-cKO), two very different paradigms. This suggests that MG miRNAs play an important role in a ubiquitous MG stress response and manipulating these miRNAs could be a first step to attenuate gliosis.
米勒胶质细胞（MG）是神经视网膜中的主要胶质细胞，在损伤后或疾病状态下会发生反应性变化。微小RNA（miRNA）是翻译抑制因子，在发育过程中调节多种过程，并且是MG功能所必需的。然而，关于反应性胶质增生中MG miRNA的情况尚无数据。因此，在本研究中，我们旨在分析光损伤7天后反应性MG中的miRNA和mRNA。以10000勒克斯的光照强度进行8小时的光损伤；这会导致神经元迅速丢失和强烈的MG反应性。使用纳米串平台分析miRNA，通过微阵列进行基因表达分析。我们将光损伤数据集与Dicer基因缺失的MG数据集进行比较，以找出异同点。我们发现：（1）光损伤7天后，绝大多数MG miRNA在反应性MG中下降。（2）光损伤后只有四种miRNA增加，其中包括miR-124。（3）光损伤后在反应性MG中上调的前10个基因包括 和 。（4）损伤7天后反应性MG中miRNA的减少类似于Dicer基因缺失的MG在一个月后的情况。（5）对两个mRNA表达数据集（光损伤和Dicer基因敲除）的比较显示，在两种条件下均有1502个基因表达，其中 、 和 是上调最明显的候选基因。（6）DIANA-TarBase v.8 miRNA:RNA相互作用工具显示，在所有网络中均发现三种miRNA，即在光损伤后以及在合并数据集中；它们是miR-125b-5p、let-7b和let-7c。综上所述，结果表明在光损伤（神经元直接损伤）后反应性MG和miRNA缺失的MG（Dicer基因敲除）这两种非常不同的模式中发生的基因调控事件存在重叠。这表明MG miRNA在普遍存在的MG应激反应中起重要作用，操纵这些miRNA可能是减轻胶质增生的第一步。
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