缺氧相关长链非编码RNA调控视网膜新生血管的作用及其分子机制研究

Retinal diseases featured by angiogenesis are the leading causes of blindness worldwide. Hypoxia is the common pathological basis on initiating angiogenesis. However, the exact mechanism of retinal angiogenesis remains unclear. Long noncoding RNAs (lncRNAs) are found to fulfill a variety of regulatory functions in gene expression recently. They are involved in regulating cell growth, apoptosis, proliferation, differentiation, and other physiological processes at epigenetic, transcriptional and post-transcriptional levels. Elucidating the function and mechanism of lncRNAs has been becoming the hot topic in biomedical research. This project aims to investigate the role and mechanism of hypoxia-related lncRNAs in regulating retinal angiogenesis under both developmental and pathological conditions. Moreover, by introducing AAV-mediated force and/or loss expression, we will assess the feasibility of suppressing retinal angiogenesis by manipulating the expression of lncRNAs. By using microarray and bioinformatics, we will explore the mechanism of lncRNAs in angiogenesis. The study may provide the evidence on lncRNAs as new therapeutic targets of retinal neovascular diseases. It may also provide clues for research in cancer and other diseases involving angiogenesis.

视网膜新生血管性疾病是一类世界性严重致盲性眼病，缺氧导致新生血管是其共同病理基础，但其发生机制复杂，目前尚未完全明确。lncRNA是一类具有广泛调控功能的非编码RNA，在表观遗传学、转录及转录后水平调节基因的表达，参与调控机体生长发育、细胞凋亡、增殖、分化等多种生理功能，是近几年的研究热点。本项目拟探讨缺氧相关的lncRNA在视网膜生理性血管发育与病理性血管新生中的作用及其机制，以重组腺相关病毒介导的基因高表达和/或RNA 干扰技术，系统探讨调节关键lncRNA抑制视网膜新生血管的可行性，采用芯片和生物信息学技术探索lncRNA的作用机制，为确立lncRNA作为视网膜新生血管性疾病治疗的新靶点提供更新的科学依据，也为恶性肿瘤等伴有新生血管的疾病研究提供借鉴。

视网膜新生血管性疾病是一类世界性严重致盲性眼病，缺氧导致新生血管是其共同病理基础，但其发生机制复杂，目前尚未完全明确。lncRNA是一类具有广泛调控功能的非编码RNA，在表观遗传学、转录及转录后水平调节基因的表达，参与调控机体生长发育、细胞凋亡、增殖、分化等多种生理功能，是近几年的研究热点。本项目首先从正常小鼠视网膜血管发育过程中（出生第3天-17天）、氧诱导病理性视网膜新生血管模型和体外缺氧和新生血管内皮细胞模型中筛选出MEG3和NEAT1两种具有生物学功能的lncRNA，通过体内和体外低表达的方法，证明了抑制这两种lncRNA可部分阻断生理性视网膜血管新生以及OIR诱导的病理性血管新生，最后通过体外实验，证明抑制MEG3和NEAT1均能显著抑制内皮细胞增殖与迁移。为靶向MEG3和NEAT1作为视网膜新生血管性疾病治疗的新靶点提供了新的科学依据。