FUNCTION OF THE VITRONECTIN RECEPTOR OF HUMAN RPE

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We propose to study ten vitronectin receptor of human retinal pigment epithelial (RPE) cells. The vitronectin receptor is a cell adhesion receptor occupying a vital position between the intracellular and extracellular milieu. One of ten fundamental features of cells from multicellular organisms is their adhesion to the extracellular matrix. Cell adhesion can modulate a number of cellular functions, such as cell growth, cell shape, phagocytosis and cell movement and seems to be involved in many biological processes, including morphogenesis, blood clotting, wound healing and metastasis of malignant cells. Cell adhesion occurs as a result of the interaction between cell surface molecules, known as "cell adhesion receptors", and he cell recognition sites of extracellular matrix proteins. RPE cells proliferate to from epiretinal membranes in pathologic conditions. We postulate that changes in cell adhesion are basic to proliferation and that our studies of vitronectin receptor function may lead to development of a rational treatment for this problem. The molecular properties of the vitronectin receptor are known in detail. We intend to carry out three principal types of functional experiments: (1) examining the properties of the vitronectin receptor in human RPE cells; (2) expressing and repressing the receptor molecules using cDNA constructs with and without modifications, then characterizing the properties of resultant molecules and transfectants; and (3) investigating the gene regulation of the receptor. The information we expect to gather from these experiments will help us to better understand the functional properties and the primary physiological function of the cell adhesion molecules. Such data will also assist us in comprehending the adhesion properties of RPE cells and their function.