Cellular movement is required during normal embryonic growth, tissue remodeling, and wound repair. Several different classes of molecules, including growth factors, cell surface receptors, metalloproteinases, cytoskeletal elements, tumor cell-derived migration factors, and extracellular matrix molecules are involved in this process. The relationships among these factors are not well understood, but they most likely involve complex interactions between many of the molecules listed above. In the study proposed here, we wish to characterize the interactions between cells and extracellular matrix in an in vitro model system (bovine corneal endothelial cells) where the cells have been induced to migrate in response to an injury. A unique aspect of this model system is that the corneal endothelial cells migrate over a complex substratum that they have elaborated, rather than in response to a single purified matrix component. Therefore, migration in this model system is much more likely to resemble the in vivo response of the cells. Work from our own laboratory and several others has implicated a specific extracellular matrix molecule, thrombospondin, as important in the migratory response. The work from our laboratory was the first to implicate thrombospondin in corneal wound healing. In the proposed research, we will determine the ability of antibodies to thrombospondin, exogenously added thrombospondin and peptides derived from thrombospondin, and proteoglycans derived from the surface of bovine corneal endothelial cells, to modulate the migratory response in our in vitro model system. It is anticipated that these studies will provide information about how cells decipher the complex information present in the extracellular matrix. These studies will also provide information that may be useful in designing therapy to stimulate healing in the corneal endothelium.
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