增生性玻璃体视网膜病变（PVR）是难治性致盲性眼病。其纤维疤痕化病理过程呈"瀑布式" 发展，其中视网膜色素上皮细胞（RPE）发生上皮-间充质细胞转换（EMT）是PVR启动和发展的关键。我们前期研究证实，在TGF-β1诱导RPE细胞发生EMT中Snail和miR-22*、miR-135b的表达发生显著变化，但是TGF-β1-miRs-EMT调控机制不清楚。miRs是内源性非编码小RNA，通过调控EMT过程决定肿瘤转移和纤维化疾病进展。PVR病理过程类似肿瘤生长和纤维化疾病。本项目将应用细胞和分子生物学等技术从RPE细胞形态与功能，PVR动物模型和临床标本三方面研究miRNA-22*和miR-135b调控RPE细胞发生EMT的机制。项目的完成将突破PVR发病机制研究中的难点问题，阐明RPE细胞向成纤维样细胞转换的调控通路，为PVR治疗提供新思路。

Proliferative vitreoretinopathy (PVR) is one of the major problems leading to blindness in patients with retinal detachments. An important event in the PVR is retinal pigment epithelial(RPE) to mesenchymal transition (EMT). Our previous studies have shown that Snail transcription factor plays a critical role in transforming growth factor-β1 (TGF-β1)-induced EMT in human RPE cells. The expression of miR-22* and miR-135b were changed significantly during this process. However, the regulatory mechanism of TGF-β1-miRNAs-EMT in RPE cells undergoing EMT is largely unknown. MicroRNAs (miRs) are endogenous, small, non-coding, regulatory RNAs. Growing evidence has indicated important roles for different miRs in regulating EMT during the development of cancer and fibrotic diseases. The PVR pathological process is similar to the development of cancer and fibrotic diseases. Therefore, we will investigate the role of miR-22* and miR-135b in EMT of RPE cells and the mechanisms which may exist. Basic molecular biology technology will be applied to conduct a full investigation and validation from RPE cell morphology and function, PVR animal models and clinical specimens. Completion of the project will clarify the regulatory mechanism of miRs in RPE cells EMT during PVR and will be a major breakthrough in the study of PVR pathogenesis. The specific inhibition of miRs may provide a new approach to treat and prevent PVR.