MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model
MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model
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DOI：
10.1371/journal.pone.0218282
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发表时间：
2019-06-12
期刊：
影响因子：
3.7
通讯作者：
Chemtob, Sylvain
中科院分区：
文献类型：
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作者：
Desjarlais, Michel;Rivera, Jose Carlos;Chemtob, Sylvain
背景缺血性视网膜病变是导致视力损害的主要原因。它们的特征是微血管变性的初始阶段和异常视网膜前新生血管(NV)的第二阶段。MicroRNAs(MiRNAs)调节基因表达，许多在正常和病理性NV中发挥作用。目的与方法利用下一代测序技术，我们分析了氧诱导视网膜病变(OIR)血管退行性变和NV期视网膜和脉络膜中miRNA的表达。结果大约20%的miRNA表达发生改变(上调或下调)；6%的miRNA在OIR大鼠的视网膜和脉络膜中高表达。在OIR诱导的血管变性阶段，miR-199a-3p、-199a-5p、-1b、-126a-3p在视网膜中的表达显著降低(>；85%)。脉络膜中miR-1523p、-142-3p、-148a-3p、-532-3p表达上调(>；200%)，miR-96-5p、-124-3p、-9a-3p、-190b-5p、-181a-1-3p、-9a-5p、-183-5p表达下调(>；70%)。在病理性NV高峰期，视网膜miR-30a-5p、-30e-5p和190b-5p显著减少(70%)，miR-30e-3p、miR-335、-30b-5p显著增加(最高达300%)。脉络膜中miR-let-7f-5p、miR-126a-5p和miR-101a-3p表达下调81%，miR-125a-5p、let-7e-5p和let-7g-5p表达上调570%。使用NGS观察到的miRNA的变化通过qRT-PCR对24个调制最多的miRNAs进行了验证。在电子计算机方法预测miRNA靶基因(使用miRSystem数据库的算法)中，发现了潜在的具有促炎、促凋亡和血管生成特性的新靶基因。结论本研究首次全面描述了OIR中视网膜/脉络膜miRNAs的特征(使用NGS技术)。我们的结果为特定miRNAs的特性和可能的治疗潜力提供了一个有价值的框架，这些miRNAs参与了眼部IR引发的炎症、血管生成和变性。
BackgroundIschemic retinopathies (IRs) are leading causes of visual impairment. They are characterized by an initial phase of microvascular degeneration and a second phase of aberrant preretinal neovascularization (NV). microRNAs (miRNAs) regulate gene expression, and a number play a role in normal and pathological NV. But, post-transcriptional modulation of miRNAs in the eye during the development of IRs has not been systematically evaluated.Aims & methodsUsing Next Generation Sequencing (NGS) we profiled miRNA expression in the retina and choroid during vasodegenerative and NV phases of oxygen-induced retinopathy (OIR).ResultsApproximately 20% of total miRNAs exhibited altered expression (up-or down-regulation); 6% of miRNA were found highly expressed in retina and choroid of rats subjected to OIR. During OIR-induced vessel degeneration phase, miR-199a-3p, -199a-5p, -1b, -126a-3p displayed a robust decreased expression (> 85%) in the retina. While in the choroid, miR-1523p, -142-3p, -148a-3p, -532-3p were upregulated (>200%) and miR-96-5p, -124-3p, -9a-3p, -190b-5p, -181a-1-3p, -9a-5p, -183-5p were downregulated (>70%) compared to controls. During peak pathological NV, miR-30a-5p, -30e-5p and 190b-5p were markedly reduced (>70%), and miR-30e-3p, miR-335, -30b-5p strongly augmented (by up to 300%) in the retina. Whereas in choroid, miR-let-7f-5p, miR-126a-5p and miR-101a-3p were downregulated by (> 81%), and miR-125a-5p, let-7e-5p and let-7g-5p were upregulated by (>570%) during NV. Changes in miRNA observed using NGS were validated using qRT-PCR for the 24 most modulated miRNAs. In silico approach to predict miRNA target genes (using algorithms of miRSystem database) identified potential new target genes with pro-inflammatory, apoptotic and angiogenic properties.ConclusionThe present study is the first comprehensive description of retinal/choroidal miRNAs profiling in OIR (using NGS technology). Our results provide a valuable framework for the characterization and possible therapeutic potential of specific miRNAs involved in ocular IR-triggered inflammation, angiogenesis and degeneration.