Biology of corneal fibrosis: soluble mediators, integrins, and extracellular vesicles.

Corneal fibrosis develops in response to injury, infection, postsurgical complications, or underlying systemic disease that disrupts the homeostasis of the tissue leading to irregular extracellular matrix deposition within the stroma. The mechanisms that regulate corneal scarring are focused heavily on the canonical transforming growth factor-β pathway and relevant activators, and their role in promoting myofibroblast differentiation. In this paper, we discuss the biochemical pathways involved in corneal fibrosis in the context of different injury models-epithelial debridement, superficial keratectomy, and penetrating incision. We elaborate on the interplay of the major pro-fibrotic factors involved in corneal scar development (e.g., transforming growth factor-β1, thrombospondin-1, and ανβ6), and explore a novel role for extracellular vesicles secreted by the wounded epithelium and the importance of the basement membrane.