MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A
MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A
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MicroRNA-18a-5p 给药通过靶向 FGF1 和 HIF1A 抑制视网膜新生血管形成
DOI：
10.3389/fphar.2020.00276
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发表时间：
2020-03-10
影响因子：
5.6
通讯作者：
Chi, Zai-Long
中科院分区：
文献类型：
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作者：
Guan, Ji-Tian;Li, Xin-Xin;Chi, Zai-Long
病理性眼部新生血管形成通常导致许多眼底疾病中的视力损害或甚至失明，所述眼底疾病包括增殖性糖尿病视网膜病变（PDR）、早产儿视网膜病变（ROP）和年龄相关性黄斑变性（AMD）。microRNA通过调节靶基因和疾病进展来调节血管生成，使其成为药物发现的一类新靶点。在这项研究中，我们使用氧诱导的增殖性视网膜病变（OIR）小鼠模型研究了miR-18 a-5 p在视网膜新生血管形成中的潜在作用。我们发现miR-18 a-5 p在幼鼠视网膜和视网膜内皮细胞中高度表达，并且在视网膜发育过程中持续下调。另一方面，miR-18 a-5 p在OIR小鼠视网膜中的病理性新血管形成期间显著增加。此外，玻璃体内给予miRNA模拟物agomiR-18 a-5 p可显着抑制OIR模型中的视网膜新生血管形成。因此，agomir-18 a-5 p显著抑制人视网膜微血管内皮细胞（HRMEC）功能，包括增殖、迁移和管形成能力。此外，我们证明了miR-18 a-5 p直接下调已知的血管生长因子，成纤维细胞生长因子1（FGF 1）和缺氧诱导因子1-α（HIF 1A），作为靶基因。总之，miR-18 a-5 p可能是病理性眼部新生血管形成的有用药物靶标。
Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.