However, Before The Onset Of The Healing Cascade There Is A Lag Phase During

However, before the onset of the healing cascade there is a lag phase during which the cells change their metabolic status, also during the lag phase a large amount of cellular reorganization and protein synthesis occurs (Lu et al 2001). Healing of the epithelium may be divided into three parts, part one involves epithelial wound repair, whereby epithelial cells flatten and migrate as an intact sheet to cover the wound. Part two involves the division of cells distal to the wound in order to repopulate the cells lost, cell stratification and differentiation of epithelial cells also occurs. In the final part, hemidesmosomes are formed as well as the synthesis and reassembly of the extracellular matrix. It has also been identified that a variety of other matrix components are synthesized and deposited in response to wounding such as fibronectin, forming a provisional matrix before the start of part one of repair (Zieske, 2001).
Stromal wound healing also occurs in phases. Firstly, keratocytes next to the area of epithelial damage undergo apoptosis, this cell death thereby initiates the entire wound healing response. Next, the keratocytes immediately neighbouring the area of apoptosis proliferate to repopulate the wound area. In this second phase, keratocytes transform into fibroblasts and move to the wounded area, these cells synthesise and deposit matrix proteins at the migration site. In the final phase, fibroblasts are transformed into myofibroblasts, which are involved in contracting the wound. This may take up to a month to occur, after which stromal remodelling occurs (Zieske, 2001).

Figure 2: The processes involved in wound healing of the cornea (Klenkler et al, 2004).
The complex cascade of wound healing is dependent on the production of numerous factors which regulate the process (Figure 2). Within a few minutes following wound development the first response of the corneal cells is the secretion of cytokines such as interleukin 1 (IL-1) and tissue necrosis factor a (TNF-a), also known as ''master
regulators'' of the response, by the wounded epithelial cells, which leads to stromal cell apoptosis (Wilson, 2001). Following this, keratocytes proliferation begins within 1224 hours and continues for several days, approximately 7 days post injury, these cells then produce elevated levels of factors such as, keratinocyte growth factor (KGF), epithelial growth factor (EGF) and hepatocyte growth factor (HGF) which stimulate epithelial cell proliferation as well as cause detached epithelial cells to migrate to the wound. It has been demonstrated that keratocytes apoptosis and necrosis also continue for at least a week after the initial wound formation. Also, a few days following the induction of apoptosis, apoptosis, necrosis, and mitosis wind down and a quiescent state is restored (Wilson, 2001).