Recent studies reported that DNA methylation was involved in retinal cell death. Methyl-CpG binding domain protein 2 (Mbd2) is one of the DNA methylation readers. Its role and mechanism of regulation remain unclear. The ischemia/reperfusion (I/R) model in mice primary culture retinal ganglion cells (RGCs) and Mbd2 knockout (Mbd2-KO) mice was used in the current study. We demonstrated that Mbd2 mediates RGC apoptosis caused by I/R injury. Mechanistically, the data suggested that Mbd2 upregulated Mbd2-associated long noncoding RNA 1 (Mbd2-AL1) via demethylation of its promoter. Furthermore, Mbd2-AL1 sponged microRNA (miR)-188-3p, thus preventing tumor necrosis factor (TNF) receptor-associated factor 3 (Traf3) downregulation and inducing RGC apoptosis. This was further demonstrated by the fact that inhibition of miR-188-3p diminished the anti-apoptosis role of Mbd2-AL1 small interfering RNA (siRNA). Finally, it showed that the apoptosis of retinal cells was attenuated, and the visual function was preserved in Mbd2-KO mice, which were associated with the Mbd2-AL1/miR-188-3p/Traf3 axis. Our present study revealed the role of Mbd2 in RGC apoptosis, which may provide a novel therapeutic strategy for retinal ischemic diseases.

中文翻译：

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Mbd2 在缺血/再灌注损伤中通过靶向 lncRNA Mbd2-AL1/miR-188-3p/Traf3 轴介导视网膜细胞凋亡


最近的研究报告称，DNA 甲基化与视网膜细胞死亡有关。甲基-CpG 结合域蛋白 2 (Mbd2) 是 DNA 甲基化读取器之一。其作用和调节机制尚不清楚。本研究使用小鼠原代培养视网膜神经节细胞（RGC）和Mbd2敲除（Mbd2-KO）小鼠的缺血/再灌注（I/R）模型。我们证明 Mbd2 介导 I/R 损伤引起的 RGC 凋亡。从机制上讲，数据表明 Mbd2 通过其启动子的去甲基化上调 Mbd2 相关的长非编码 RNA 1 (Mbd2-AL1)。此外，Mbd2-AL1 海绵化 microRNA (miR)-188-3p，从而防止肿瘤坏死因子 (TNF) 受体相关因子 3 (Traf3) 下调并诱导 RGC 凋亡。抑制 miR-188-3p 会减弱 Mbd2-AL1 小干扰 RNA (siRNA) 的抗凋亡作用，这一事实进一步证明了这一点。最后表明，Mbd2-KO小鼠视网膜细胞凋亡减弱，视觉功能得以保留，这与Mbd2-AL1/miR-188-3p/Traf3轴有关。我们目前的研究揭示了 Mbd2 在 RGC 凋亡中的作用，这可能为视网膜缺血性疾病提供新的治疗策略。