Responses to Injury and the Role of Stem Cells in Corneal Repair
Severe trauma to the cornea can result in scarring and blindness if the corneal tissue is not restored appropriately. The commonest causes of corneal injury include infections, thermal, chemical burns and mechanical abrasions, but also hereditary and immune disorders leading to opacification, conjunctivalization, neovascularization, and ulceration. In Sect. 4.5 the clinical applications of stem cells in corneal wound healing will be discussed but first an overview is given of the consequences and the responses to corneal injury. Since the layers of the cornea are so diverse in their embryology, physiological properties and regenerative capacities, the ability of a cornea to recover from injury is dependent on both the surface area of the injury and the depth of the penetration.
In case of a superficial injury only the epithelium is affected. If the epithelial barrier is breached, an immediate physiological, biochemical and anatomical healing response is initiated. Mitochondrial energy production is increased, cell membrane extensions are formed and hemidesmosomal adhesions to the basement membrane are lost (DelMonte and Kim 2011). The proliferative activity in the limbus rises dramatically, up to ninefold, which persists for up to 48 h. During this time, the proliferative activity in the peripheral and central cornea doubles, until wound closure (Cotsarelis et al. 1989; Lavker et al. 1998). This is thought to be the result of the proliferation of limbal epithelial stem cells and transient multiplication of basal cells (Lehrer et al. 1998; Daniels et al. 2001). The first phase of the response to injury is nonmitotic. The sheet of residual epithelial cells starts migrating and spreading and cells at the advancing edge of a wound extend the sheet to cover the wound (Soong 1987). Matsuda et al. demonstrated that larger epithelial wounds close at a faster rate than smaller ones, with a speed of up to 80 pm per hour (Matsuda et al. 1985). In the second phase, the epithelial cell population is restored by reconstitutive mitosis of the basal cells, the TACs and the limbal stem cells (Wiley et al. 1991). If the limbus is severely damaged and devoid of its stem cell population, this process cannot take place and consequently corneal wounds do not heal adequately.