The Corneal Epithelial Cells Also Release Tissue Plasminogen Activator Onto

The corneal epithelial cells also release tissue plasminogen activator onto the surface of the eye, resulting in the production of plasmin which is thought to activate TGF-b, which in turn induces proliferation and migration of corneal stromal fibroblasts. The epithelial cells can also communicate with the fibroblasts, this positively affects epithelial tissue recovery through the production of further growth factors. These events occur very quickly, within hours of onset of injury to re-establish barrier function over the wound. The production and release of PDGF and TGF-b from the epithelium into the stroma, and an increased presence in tears also enables the stimulation of stromal cell proliferation. The presence of TGF-b found in the later stages of stromal healing, inhibits HGF and KGF expression, this stops excess epithelial cell proliferation (Klenkler et al, 2004).
Eight hours following injury, a provisional fibronectin matrix (composed of actin filaments and focal contacts) is synthesised and accumulates at the site of the wound. Corneal epithelial cells proliferate at the injury site and also produce factors which promote cell to cell adhesion. Once confluence of cells is developed, they are then promoted to differentiate forming a stratified epithelium. Following the development of this epithelium the fibronectin matrix disappears and the normal basement membrane composition of collagen and laminin is replaced (Klenkler et al, 2004). Remodelling of the collagen matrix of the stroma also occurs in order to eliminate scar tissue, after which the epithelium returns to a normal thickness (Wilson, 2001).
Beginning 1224 hr following injury, an influx of inflammatory cells into the cornea from the limbal blood vessels occurs. This occurs following the activation of the different growth factors which bind to receptors on keratocytes, which in turn stimulate production of factors chemotactic to inflammatory cells. Immune cells which eliminate debris and microbes that may breach the injured surface and gain entry to the corneal stroma thus move to the site of the wound, they also release PDGF enabling the mediation of the healing process (Wilson, 2001).
After the injury has been established and healing processes have occurred, in the weeks and months after this process the cornea then returns to a normal state, inflammatory and myofibroblast and fibroblast cells are eliminated through apoptosis and the stroma is restored. The expression of growth factor receptors and proteins also return to the levels they were before wound development. The stromal re-modelling process can possibly carry on for years and result in the removal, at least in part of the stromal scars. Some studies have indicated that apoptosis of some stromal cells can also still be detected at a very low rate approximately three months after the initial injury (Wilson, 2001).