lncRNA Ttc3-209 Promotes the Apoptosis of Retinal Ganglion Cells in Retinal Ischemia Reperfusion Injury by Targeting the miR-484/Wnt8a Axis.
lncRNA Ttc3-209 Promotes the Apoptosis of Retinal Ganglion Cells in Retinal Ischemia Reperfusion Injury by Targeting the miR-484/Wnt8a Axis.
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lncRNA Ttc3-209通过靶向miR-484/Wnt8a轴促进视网膜缺血再灌注损伤中视网膜神经节细胞凋亡
DOI：
10.1167/iovs.62.3.13
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发表时间：
2021-03-01
影响因子：
4.4
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Zhang R;Feng Y;Lu J;Ge Y;Li H
目的视网膜缺血再灌注损伤(RIR)后，视网膜神经节细胞(RGCs)的凋亡可导致不可逆的视功能损害。利用LncRNA芯片技术，我们选择了LncRNA TTC-209，并研究了其在缺血再灌注(I/R)诱导的视网膜节细胞凋亡中的作用。方法应用含10µM抗霉素A和2µM钙离子载体的Hank‘s平衡盐液制作视网膜神经节细胞缺血模型。通过角膜插管将眼压升高至120毫米汞柱1小时，以诱导小鼠RIR；随后进行再灌流。实时荧光定量聚合酶链式反应(Real-Time Quantity PCR，RT-PCR)检测长链非编码核糖核酸(LncRNA)、微核糖核酸(microRNA，miRNA)和靶基因mRNA的表达水平。用Western blotting、流式细胞仪、免疫荧光染色和TUNEL法检测细胞凋亡。双荧光素酶报告分析和FISH被用来鉴定连接lncRNAs、miRNAs和靶基因的内源竞争RNA(Cerna)机制。我们还使用暗视视网膜电图检查来评估接受治疗的小鼠的视觉功能。结果LncRNA Ttc3-209在RGCs I/R损伤后表达显著上调，并在I/R诱导的RGCs凋亡中发挥促凋亡作用。从机制上讲，lncRNA Ttc3-209是一种Cerna，与miR-484竞争性结合，上调其靶标(Wnt8a MRNA)的翻译，从而促进RGCs的凋亡。结论下调LncRNA Ttc3-209的表达对RGCs的凋亡具有保护作用。这可能为预防RIR损伤引起的RGC细胞凋亡提供新的治疗选择。
Purpose Apoptosis of the retinal ganglion cells (RGCs) can cause irreversible damage to visual function after retinal ischemia reperfusion injury (RIR). Using a lncRNA chip assay, we selected lncRNA Ttc-209 and characterized its role in RGCs during ischemia reperfusion (I/R)–induced apoptosis. Methods We created an ischemic model of RGCs by applying Hank's balanced salt solution containing 10 µM antimycin A and 2 µM calcium ionophore for 2 hours. RIR was induced in mice by elevating the intraocular pressure to 120 mm Hg for 1 hour by cannulation of the cornea; this was followed by reperfusion. Real-time quantitative PCR was used to detect the expression levels of long noncoding RNA (lncRNA), microRNA (miRNA), and target gene mRNA. Western blotting, flow cytometry, immunofluorescent staining, and TUNEL assays were performed to detect cell apoptosis. Dual-luciferase reporter assays and FISH were used to identify endogenous competitive RNA (ceRNA) mechanisms that link lncRNAs, miRNAs, and target genes. We also used scotopic electroretinography examinations to evaluate visual function in treated mice. Results lncRNA Ttc3-209 was significantly upregulated after I/R injury and played a proapoptotic role in RGCs during I/R-induced apoptosis. Mechanistically, lncRNA Ttc3-209 is a ceRNA that competitively binds to miR-484 and upregulates the translation of its target (Wnt8a mRNA), thus promoting apoptosis in RGCs. Conclusions Reducing the expression of lncRNA Ttc3-209 had a protective effect against apoptosis in RGCs. This may provide a new therapeutic option for the prevention of RGC apoptosis in response to RIR injury.
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