Emerging in vitro models of corneal stromal fibrosis: Toward human-relevant platforms for anti-scarring therapeutics

Abstract Corneal stromal fibrosis, characterized by the aberrant transformation of keratocytes into contractile, extracellular matrix-secreting myofibroblasts, is a major cause of irreversible visual impairment worldwide. Despite extensive studies in animal models, interspecies differences in immune regulation, stromal architecture, and wound healing limit their translational relevance. This review highlights recent advances in human-relevant in vitro models that aim to overcome these challenges. In vitro models increasingly mimic critical features of corneal stromal fibrosis, including keratocyte–myofibroblast transition, extracellular matrix remodeling, and stromal contraction. Collagen-based matrices and macromolecular crowding approaches enhance extracellular matrix deposition and provide more faithful fibrotic microenvironments. Decellularized scaffolds preserve stromal architecture, while stem cell-derived organoids recapitulate tissue complexity and chronic fibrotic responses. Microfluidic cornea-on-chip platforms integrate mechanical and biochemical cues, enabling dynamic modeling and real-time analysis. Together, these advances expand opportunities for mechanistic insight and preclinical anti-fibrotic drug screening in physiologically relevant systems. In vitro models of corneal stromal fibrosis are rapidly progressing, offering promising platforms for anti-fibrotic drug discovery and translational ophthalmology. Yet challenges in standardization, scalability, and integration of stromal–immune interactions must be addressed to bridge preclinical findings with clinical application.