The corneal stroma has a highly organized structure and lower density of cells than the epithelium and as such, has a lower capacity for repair and regeneration. Injuries severe enough to breach the epithelium and Bowman’s membrane therefore have a higher likelihood of inducing a permanent scar.
Among the commonest causes of stromal injury are infections, thermal, chemical and mechanical abrasions, hereditary and immune disorders. Injury that leads to the loss of specific isoforms of collagen, such as collagen type IV from the epithelial basement membrane, has been associated with an overexpression of matrix metalloproteinases in combination with the activation of inflammatory cytokines. This subsequently leads to the formation of scar tissue and corneal haze (Gabison et al. 2009).
Role of MSCs in Stromal Wound Healing
The MSCs respond to corneal injury and inflammation by mobilization, migration and colonization (Kang et al. 2012). The process of stromal wound healing is activated when a corneal injury penetrates the Bowman’s or Descemet’s membrane and infiltrates the stroma leading to edema and corneal haze. Stromal wound healing involves a variety of growth factors, cytokines and chemokines secreted by the overlying, injured epithelium and keratocytes (Netto et al. 2005). The process is carried out in three phases: (i) repair, (ii) regeneration and (iii) remodelling (Fini and Stramer 2005). Firstly, some of the keratocytes within the area of injury undergo apoptosis, while others are activated and differentiate into a fibroblast-like phenotype (Wilson et al. 1996; Stramer et al. 2003). The new ‘repair’ fibroblasts can proliferate and synthesize the components required for the formation of new extracellular matrix. After 1-2 weeks, the stroma at the site of injury is invaded by myofibroblasts which promote remodelling by further differentiating into the ‘repair’ type fibroblasts possessing contractile properties while expressing a wide array of proteins. It has been proposed that the collagen in the stromal wound is reorganized by matrix metalloproteinases (MMPs) which remodel the ECM and the interactions between the matrix and the cells (Maguen et al. 2002; Fini and Stramer 2005; Gabison et al. 2005). The highly light-scattering myofibroblasts de-differentiate once wound healing is complete and transparency of the cornea should return. If the repair fibroblasts differentiate into scar keratocytes (laying down irregularly spaced collagen) instead of myofibroblasts, they cannot de-differentiate and contribute to a permanent corneal scar (Shah et al. 2008).