申请人前期工作新发现长链非编码RNA（lncRNA）p22857很可能通过靶基因TSP1调节人晶状体上皮细胞自噬过程。为了证实并深入研究lncRNA p22857/TSP1通路调控自噬在人晶状体发育及白内障中的作用及机制，本项目拟在本研究团队近期成功创立的体外晶状体（LBs）诱导新方法—“荷包蛋”法的基础上构建人晶状体混浊模型，模拟自噬异常诱发白内障发病进程，并通过lncRNA芯片、CRISPER-Cas9、siRNA、RNA pull down、lncRNA FISH等实验手段，在细胞、LB整体及病人水平探索lncRNA p22857/TSP1调控自噬在白内障发生发展中的作用及机制。本课题构建的LB混浊模型即避免了动物疾病模型的种属差异、模拟白内障在体发展进程，又为人来源lncRNA p22857调控白内障病理机制研究提供了可能性。研究结果将为白内障治疗新药物的寻找提供新思路和理论基础。

In recent studies, we found that the autophagy process in human lens epithelial cells (HLECs) was likely regulated by the newly discovered long non-coding RNA p22857 (lncRNA p22857) which could activate CD47 signaling through its target gene TSP1.In order to further prove and investigate the molecular mechanism of lncRNA p22857/TSP1 pathway in human lens development and cataractogenesis through autophagy, we’d like to establish a human lens opacity (cataract) model based on our newly developed protocol for functional lentoid bodies (LBs) generation using human induced pluripotent stem cells (iPSCs) in vitro—‘fried egg” method by which LBs exhibiting both structural and functional properties similar to human lens could be generated. Molecular mechanisms were then explored using techniques such as mRNA+lncRNA co-expression microarray, CRISPER-Cas9, siRNA, RNA pull down, mass spectrometry assay, lncRNA FISH and et al. The human lens opacity (cataract) model that were established in this study not only could the in vivo process of cataract be mimicked, but also could the species differences which are faced by researchers be avoided. Moreover, it provides the possibility in search for the molecular mechanism of lncRNA p22857 in cataract in human. Exploration may lead to clinical opportunities for new therapy and medicine target in cataract.