CELL-ASSOCIATED PROTEOGLYCANS OF RETINAL PERICYTES AND ENDOTHELIAL-CELLS - MODULATION BY GLUCOSE AND ASCORBIC-ACID

Abnormalities of retinal pericytes and endothelial cells are prominent features of diabetic retinopathy. In this study, we used cultures of bovine retinal cells to examine the regulation of cell-associated prot eoglycans, a class of highly sulfated macromolecules important in the regulation of cell growth. Bovine retinal pericytes and endothelial ce lls were radiolabeled with (SO4)-S-35 and cell-associated proteoglycan s were removed from the cell surface, quantified, and characterized. T he effects of high glucose concentration (25 mM), phorbol 12,13-dibuty rate (PDBu, 0.1 mu M), and ascorbic acid (0.1 mM) on cell-associated p roteoglycans and growth of these cells were studied. Our results showe d that both the ionically bound and the membrane-intercalated forms of cell-associated proteoglycans are present on retinal cells. The predo minant cell-associated proteoglycan of pericytes is chondroitin sulfat e and for endothelial cells it is heparan sulfate. High glucose concen tration and ascorbic acid increased the cell-associated proteoglycans on pericytes but reduced them on endothelial cells. In contrast to thi s divergent trend, high glucose concentration and ascorbic acid inhibi ted the growth of both pericytes and endothelial cells. The effects of high glucose on retinal cell-associated proteoglycans were mimicked b y PDBu added in a manner to stimulate protein kinase C activity. We co nclude that cell-associated proteoglycans are present on retinal peric ytes and endothelial cells. High glucose concentration and ascorbic ac id affect cell-associated proteoglycans of these two cell types in opp osite directions, whereas both suppress the growth of the two cell typ es. Therefore, it is not likely that high glucose concentration and as corbic acid change the rate of retinal cell growth directly by affecti ng cell-associated proteoglycan levels. (C) 1994 Academic Press, Inc.