YAP1 inhibition delays the progression of posterior capsular opacification through attenuation of lens epithelial-mesenchymal transition

The main causes of posterior capsular opacification (PCO) are the proliferation, migration, and epithelial-mesenchymal transition (EMT) of leftover lens epithelial cells (LECs), though the exact mechanisms of EMT in PCO are not completely known. This research sought to determine whether PCO progression depends on Yes-associated protein 1 (YAP1) activation and EMT in LECs. We conducted gain- and loss-of-function experiments in human lens epithelial cells (HLE-B3) using YAP1-overexpressing plasmids and siRNA-YAP1. Cell migration was tested with a scratch wound assay, and Hippo/YAP signaling and EMT markers were analyzed via qPCR, Western blot, and immunocytochemistry. HLE-B3 cells were exposed to transforming growth factor-beta 2 (TGF-β2) and the YAP1 inhibitor verteporfin (VP) to evaluate cell proliferation, migration, and molecular expression using CCK-8, scratch assay, qPCR, and Western blot. A rabbit model for PCO was developed to test VP's effectiveness, evaluated by slit-lamp photography, H&E staining, immunofluorescence, and Western blotting for YAP1 and EMT-related proteins. In vitro, YAP1 overexpression increased TEAD2 and BIRC5, promoting EMT, while YAP1 knockdown reduced these proteins, inhibiting EMT. VP treatment decreased HLE-B3 proliferation and migration. Inhibiting YAP1 and its downstream targets, CTGF and BIRC5, suppressed EMT. In vivo, VP significantly delayed PCO progression in rabbits and decreased YAP1, α-SMA, and vimentin expression. These results suggest that YAP1 facilitates EMT in lens epithelial cells through the Hippo/YAP pathway, and its inhibition could be a promising strategy for PCO treatment.