Cell Migration along the Basement Membrane during Wound Repair. The Corneal Endothelium as a Model System

Abstract

The vertebrate corneal endothelium serves as a model system for investigating the role of cell migration during wound repair along the natural basement membrane. As a tissue monolayer, the cells reside on their basement membrane, Descemet’s membrane, which serves to modify many cellular behaviors during the injury-induced migratory response. Because the tissue is not directly dependent on either blood or nerve supplies, it is readily amendable to organ culture, where it can be easily maintained and experiments performed on the cells in situ. In addition, results obtained from work using tissue cultured corneal endothelial cells have augmented our understanding of the various pathways that are used for triggering cell movement during in vitro wound repair. The initiation of a migratory response during wound repair involves a multitude of various cellular mechanisms and structural changes that result in the activation of several biochemical pathways and modifications to cell shape as well as the reorganization of the actin cytoskeleton. These changes provide a means for the endothelial cell to translocate along Descemet’s membrane into the wound region in order to permit the repopulation of the area with the eventual reestablishment of an intact and functional monolayer. Many of these biochemical and morphological alterations appear to be mediated by various growth factors such as fibroblast growth factor, epidermal growth factor and transforming growth factor-beta. Various biochemical pathways are stimulated after an injury, including phospholipase C, phosphatidylinositol-3 kinase, protein kinase C, Rho, Rac, cdc42 and arachidonic acid metabolism which mediate several events during wound repair such as cell proliferation, epithelial-mesenchymal transition, spreading and the extension of cellular processes. In addition, despite residing on a basement membrane endothelial cells respond to injury by secreting various extracellular matrix components at the cell/basement membrane interface that aids in mediating their movement along Descemet’s membrane, which also appears to be regulated in part by protease activity. This review discusses the role of migration in corneal endothelial wound healing. How movement is modified when it occurs during in vitro as opposed to in vivo or organ cultured wound healing will also be examined as will the differences between the cellular responses to large versus small sized wounds.