Regulation of the corneal myofibroblast phenotype

After corneal wounding, keratocytes are replaced by fibroblasts and myofibroblasts. We have investigated the origin of corneal myofibroblasts in a cell culture model. When fibroblasts are plated at low density (5 cells/mm²), myofibroblasts differentiate as a result of the additive effects of absent cell-cell contact and autocrine TGF-β (Masur et al Mol Biol Cell 6:208a, 1995). In contrast, fibroblasts seeded at high density (500 cells/mm²) are refractory to TGF-β and remain fibroblasts. These findings suggest that wound-induced disruption of cell-cell contacts may act in situ as a stimulus for myofibroblast differentiation from fibroblasts. For insight into the roles of these cell types in the cornea, we investigated phenotypic markers in corneal fibroblasts and myofibroblasts in culture: α-smooth fibronectin receptor junction proteins gelatinases muscle actin secreted keratocyte - -* connexin43* latent MMP-2* fibroblast - +* connexin43 MMP-1.-2.-9* myofibroblast + ++ cadherin latent MMP-2 * Masur et al IOVS 34:2690, 1993; Jester et al 35:730, 1994; Fini & Girard 31:1779, 1990. From these data, we conclude that myofibroblasts have a primary role in wound closure by virtue of the expression of a contractile form of actin, their cadherin-based cell-cell junctions and enhanced integrin-based cell-matrix adhesions. In contrast, fibroblasts play a matrix degradative role by virtue of their gelatinase secretion. In addition, communication between fibroblasts is achieved by having connexin43-based cell-cell junctions, rather than cadherin. Thus, myofibroblasts and fibroblasts, although distinct cell types, appear to work in a concerted effort in corneal wound healing.