Corneal myofibroblast biology and pathobiology: Generation, persistence, and transparency

Important advances have led to a better understanding of the biology and pathobiology of corneal myofibroblasts and their generation after surgery, injury, infection and disease. Transforming growth factor (TGF) beta, along with platelet-derived growth factor (PDGF) and interleukin (IL)-1, has been shown to regulate myofibroblast development and death in in-vitro and in-situ animal models. The myofibroblast precursor cells regulated by these cytokines include both keratocyte-derived and bone marrow-derived cells. Cytokines that promote and maintain myofibroblasts associated with late haze after photorefractive keratectomy are modulated in part by the epithelial basement membrane functioning as barrier between the epithelium and stroma. Structural and functional defects in the basement membrane likely lead to prolonged elevation of TGFβ, and perhaps other cytokine, levels in the stroma necessary to promote differentiation of myofibroblasts. Conversely, repair of the epithelial basement membrane likely leads to a decrease in stromal TGFβ levels and apoptosis of myofibroblasts. Repopulating keratocytes subsequently reorganize the associated fibrotic extracellular matrix deposited in the anterior stroma by the myofibroblasts. Investigations of myofibroblast biology are likely to lead to safer pharmacological modulators of corneal wound healing and transparency.

► Corneal myofibroblasts and the matrix they produce causes corneal opacity.
► The corneal epithelium and basement membrane have key roles in generation of myofibroblasts.
► Corneal myofibroblasts can be generated from either keratocyte-derived or bone marrow-derived precursors.