The transforming growth factor-beta (TGFB) plays an essential role in the pathogenesis of some ophthalmologic diseases, including neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR). TGFB activates the transcription factors SMAD2 and SMAD3 via the TGFB receptor, which together activate several genes, including VEGFA. TGFB treated ARPE-19 cells show an increased proliferation rate and undergo epithelial to mesenchymal transition (EMT). Since microRNAs (miRNAs) are capable of inhibiting the translation of multiple genes, we screened for miRNAs that regulate the TGFB signalling pathways at multiple levels. In this study, we focused on two miRNAs, miR-302d and miR-93, which inhibit TGFB signalling pathway and therefore TGFB-induced EMT transition as well as VEGFA secretion from ARPE-19 cells. Furthermore, we could show that both miRNAs can retransform TGFB-stimulated mesenchymal ARPE-19 cells towards the morphological epithelial-like state. Taken together, transient overexpression of these miRNAs in RPE cells might be a promising approach for further translational strategies.

转化生长因子-β（TGFB）在某些眼科疾病的发病机理中起着至关重要的作用，包括新血管性年龄相关性黄斑变性（nAMD）和增生性玻璃体视网膜病变（PVR）。TGFB通过TGFB受体激活转录因子SMAD2和SMAD3，后者共同激活包括VEGFA在内的多个基因。TGFB处理的ARPE-19细胞显示出增高的增殖率，并经历了上皮向间质转化（EMT）。由于microRNA（miRNA）能够抑制多个基因的翻译，因此我们筛选了在多个水平上调节TGFB信号通路的miRNA。在这项研究中，我们集中于两个miRNA，miR-302d和miR-93，它们抑制TGFB信号通路，因此抑制TGFB诱导的EMT转变以及ARPE-19细胞的VEGFA分泌。此外，我们可以证明这两种miRNA都可以将TGFB刺激的间充质ARPE-19细胞重新转化为形态上皮样状态。综上所述，RPE细胞中这些miRNA的瞬时过表达可能是进一步翻译策略的有前途的方法。