Abstract
Corneal transparency is achieved following an injury, through a well-coordinated process of epithelial reorganization and stromal extracellular matrix (ECM) remodeling; corneal scars result from unchecked fibrosis during healing. Tenascin-C (TnC) is an important player in inflammation, healing and ECM remodeling. The fibronectin type III repeat region of TnC (Tn fn) interacts with cell surface receptors and growth factors, generating an array of cell signalling events. We aimed to determine the domain-specific role of Tn fn repeats spanning the region 1–5 (Tn fn 1–5) in the context of corneal wound healing, using corneal epithelial cells, corneal fibroblasts, as well as ex vivo alkali-injured goat corneal cultures. We demonstrate that Tn fn 5 can serve as an anti-fibrotic molecule, promoting effective corneal wound healing through increased proliferation of epithelial cells, and downregulation of expression of fibrotic markers and ECM proteins. Tn fn 5 also inhibits corneal fibroblasts from developing contractile ability in the process of fibrosis. In ex vivo alkali-injured corneas, Tn fn 5 promotes corneal wound healing while inhibiting myofibroblast generation, through inhibition of fibronectin polymerization and matrix assembly. The highlight of our study is that Tn fn 5 has an anti-fibrotic effect and can be useful in corneal wound therapy.