Novel Insight of Posterior Capsule Opacification: The Role of Lens Epithelial Cell Senescence

ABSTRACT Background Posterior capsule opacification (PCO), the most common complication following cataract surgery, results from the proliferation, migration and epithelial–mesenchymal transition (EMT) of residual lens epithelial cells (LECs), typically driven by postoperative inflammatory and growth factor changes. However, delayed‐onset PCO, occurring years after surgery without obvious inflammation, suggests the involvement of additional mechanisms, with senescent cells identified as contributors to EMT. This study investigates the role of LEC senescence in PCO development. Methods Transcriptomic data from the Gene Expression Omnibus (GEO) were analysed to identify senescence‐associated pathways in PCO. Rabbit PCO models and oxidative stress‐induced senescent SRA01/04 LECs were treated with dasatinib and quercetin (DQ) to target senescent cells and inhibit the senescence‐associated secretory phenotype (SASP). Senescence, SASP and EMT biomarkers were assessed by qPCR, immunofluorescence and Western blotting. Cell migration, proliferation and apoptosis were analysed through wound healing, Transwell and flow cytometry assays. Results RNA sequencing from GEO revealed a significant correlation between senescence and PCO. In vitro, oxidative stress‐induced senescent LECs exhibited increased EMT biomarkers, including vimentin and α‐SMA. In a rabbit PCO model, senescence‐ and SASP‐related genes (p53, MMP3 and IL‐6) and proteins were upregulated. DQ treatment reduced senescence and EMT by inhibiting multiple EMT‐related signalling pathways, especially the PI3K‐Akt pathway (p‐PI3K, p‐Akt), leading to a significant reduction in PCO volume. Conclusions LEC senescence plays a key role in PCO development. DQ effectively targets multiple EMT signalling pathways, particularly PI3K‐Akt, and shows promise as a strategy for the prevention and management of PCO.