Pamrevlumab inhibits posterior capsule opacification via selective CTGF/β-catenin axis modulation and collagen-1 suppression in primary pediatric LECs

Posterior capsular opacification (PCO) arises from fibrotic activation of residual lens epithelial cells (LECs) after cataract surgery. Connective tissue growth factor (CTGF) serves as a pivotal downstream amplifier of transforming growth factor-β2 (TGF-β2)-induced signaling, promoting the fibrotic cascade. This study evaluated the effect of pamrevlumab, a CTGF-neutralizing antibody, on profibrotic signaling in a primary pediatric LEC culture model. β-catenin, ERK phosphorylation, and collagen type I (COL-1) expression were analyzed by immunofluorescence, whereas proliferation and migration were assessed using a wound-healing assay. Pamrevlumab significantly suppressed β-catenin nuclear activation ( p = 0.023) and COL-1 expression ( p < 0.001) in a dose-dependent manner, whereas ERK signaling showed no significant difference ( p > 0.05). Regression analysis estimated a potent reduction of 608.40 AU in COL-1 expression for every 1 μg/mL increase in pamrevlumab dose ( p = 0.001). These results indicate that pamrevlumab ameliorates CTGF/β-catenin-associated profibrotic signaling and prevents coordinated fibrotic responses in primary human LECs. Although this study is limited to an in vitro mechanistic context, it ultimately lays the preclinical groundwork for further translational exploration of CTGF-targeted approaches for the mitigation of PCO.