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Abstract：
In the pathogenesis of age-related macular degeneration, long non-coding RNAs have become important regulators. This study aimed to investigate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of choroidal neovascularization (CNV) and the underlying mechanisms. The in vivo and in vitro model of CNV was established using laser-induced mouse CNV model and human choroidal vascular endothelial cells (HCVECs) exposed to hypoxia respectively. We explore the role of MALAT1 in the pathogenesis of CNV by using the small interference RNA both in vivo and in vitro. MALAT1 expression was found to be upregulated in the retinal pigment epithelial-choroidal complexes. MALAT1 knockdown inhibited CNV development and leakage in vivo and decreased HCVECs proliferation, migration, and tube formation in vitro. MALAT1 performed the task as a miR-17-5p sponge to regulate the expression of vascular endothelial growth factor A (VEGFA) and E26 transformation specific-1 (ETS1). This study provides a new perspective on the pathogenesis of CNV and suggests that the axis MALAT/miR-17-5p/VEGFA or ETS1 may be an effective therapeutic target for CNV.
摘要：
在年龄相关性黄斑变性的发病机制中，长链非编码RNA已成为重要的调节因子。本研究旨在探讨转移相关肺腺癌转录本1(MALAT1)在脉络膜新生血管(CNV)进展中的作用及其机制。采用激光诱导的小鼠CNV模型和缺氧条件下的人脉络膜血管内皮细胞(HCVECs)分别建立CNV的体内和体外模型。我们通过在体内和体外使用小干扰RNA来探索MALAT1在CNV发病机理中的作用。发现MALAT1表达在视网膜色素上皮-脉络膜复合物中上调。MALAT1敲低抑制体内CNV的发展和渗漏，减少HCVECs的增殖，迁移,和体外试管形成。MALAT1作为miR-17-5p海绵执行任务，以调节血管内皮生长因子A（VEGFA）和E26转化特异性1（ETS1）的表达。本研究为CNV的发病机制提供了新的视角，提示MALAT/miR-17-5p/VEGFA或ETS1轴可能是CNV的有效治疗靶点。
