Cross-organ translation of antifibrotic strategies from skin and lung fibrosis to glaucoma filtration surgery

Filtering bleb scarring after glaucoma filtration surgery (GFS) remains the leading cause of surgical failure, and current antimetabolites are limited by non-selective cytotoxicity that restricts their long-term use. Research on skin and lung fibrosis has accumulated extensive experience in antifibrotic mechanisms and therapeutic approaches. These tissues share a common transforming growth factor-beta (TGF-β)-driven program of fibroblast activation and extracellular matrix (ECM) remodeling with Tenon capsule fibroblasts, providing a theoretical basis for translating antifibrotic strategies across organs. From a cross-organ translational medicine perspective, this review systematically summarizes progress in translating antifibrotic research from skin and lung fibrosis to antiscarring therapy for GFS, focusing on four aspects: shared fibrotic mechanisms; repurposed approved drugs and emerging molecular targets; local drug delivery systems (DDS); and ophthalmology-specific translational challenges. It also highlights mechanotransduction via Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), lysyl oxidase (LOX)-mediated ECM crosslinking, and the translational potential of local sustained-release delivery in filtering blebs. Building on this foundation, we propose that multi-target combination therapy, precision local delivery, and individualized antiscarring strategies based on biomarkers such as aqueous humor TGF-β 2 may represent important future directions for improving the long-term success rate of GFS.