ENDOGENOUS LECTINS OF THE RETINAL PIGMENT EPITHELIUM

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As with disease processes in other tissues, disease processes involving the RPE often are characterized by changes in adhesive contracts, unregulated proliferation, or a defect in cell recognition mechanisms. These basic processes are not mutually exclusive, and are often functionally related. A common feature of these cellular activities is that they often involve the activity of carbohydrate binding proteins, or lectins. Thus, roles for lectins in cell recognition, proliferation, and adhesion are currently the focus of vigorous study in many fields of cell and molecular biology. As a result, important functional roles have been identified for lectins in such diverse physiological processes as gamete interaction, hepatic function, and inflammation. Lectins may be important for retinal function as well, as changes in cell surface carbohydrate recognition systems have been implicated in several ocular disorders. However, it would appear from the literature that relatively little is known specifically about endogenous retinal lectins. We have recently purified two galactose-binding proteins from cultures of human RPE cells, which are tentatively identified as PEL-70 and PEL-210/47. Preliminary evidence suggests that a galactosyl recognition system involving at least one of these molecules may play a role in the regulation of RPE cell proliferation, a key feature of disorders such as proliferative vitreoretinopathy. It is our goal to understand how the PEL proteins are involved in this and other cell functions, and to relate this knowledge to the disease process in the eye. To achieve this goal, we propose to use immunological approaches to determine when and where PELs are expressed in the cell, under normal conditions and otherwise. We will examine the potential of PELs as cell recognition and/or adhesion molecules, and as regulators of cell migration and proliferation. Finally, we will dissect the PEL molecules by chemical and enzymatic means to identify functional domains. Knowledge gained from the proposed research may help us to understand, detect, and hopefully correct abberant RPE cell behavior in the future.