The corneal fibroblast: The Dr. Jekyll underappreciated overseer of the responses to stromal injury

Purpose: To review the functions of corneal fibroblasts in wound healing.Methods: Literature review.Results: Corneal fibroblasts arise in the corneal stroma after anterior, posterior or limbal injuries and are derived from keratocytes. Transforming growth factor (TGF) 01 and TGF02, along with platelet-derived growth factor (PDGF), are the major modulators of the keratocyte to corneal fibroblast transition, while fibroblast growth factor (FGF)-2, TGF03, and retinoic acid are thought to regulate the transition of corneal fibroblasts back to keratocytes. Adequate and sustained levels of TGF01 and/ or TGF02, primarily from epithelium, tears, aqueous humor, and corneal endothelium, drive the development of corneal fibroblasts into myofibroblasts. Myofi-broblasts have been shown in vitro to transition back to corneal fibroblasts, although apoptosis of myofibroblasts has been documented as a major contributor to the resolution of fibrosis in several in situ corneal injury models. Corneal fibroblasts, aside from their role as a major progenitor to myofibroblasts, also perform many critical functions in the injured cornea, including the production of critical basement membrane (BM) components during regeneration of the epithelial BM and Descemet's membrane, production of non-basement membrane-associated stromal collagen type IV to control and downregulate TGF0 effects on stromal cells, release of chemotactic chemokines that attract bone marrow-derived cells to the injured stroma, production of growth factors that modulate regeneration and maturation of the overlying epithelium, and production of collagens and other ECM components that contribute to stromal integrity after injury.Conclusions: Corneal fibroblasts are major contributors to and overseers of the corneal response to injuries.

Automated summary

Corneal fibroblasts play a crucial role in wound healing, originating from keratocytes.Transforming growth factor (TGF)-01 and TGF02, along with platelet-derived growth factor (PDGF), regulate the transition of keratocytes to corneal fibroblasts.Coronal fibroblasts perform various functions in damaged cornea, including basement membrane (BM) regeneration, control of TGF0 effects on stromal cells, attraction of bone marrow-derived cells, modulation of epithelium regeneration, and contribution to stromal integrity.