INHIBITION OF CELL-INDUCED VITREOUS CONTRACTION BY SYNTHETIC PEPTIDE DERIVED FROM THE COLLAGEN RECEPTOR-BINDING SEQUENCE

Cell-mediated tractional retinal detachment (TRD) is the end result of various intraocular proliferative disorders. Interactions between cel ls and extracellular matrix via cellular surface receptors, integrins, play an important role. Anti-adhesion therapy has been suggested as a promising way to treat the integrin-dependent pathological events. We tested three synthetic peptides, Gly-Arg-Gly-Asp-Ser (GRGDS), derived from the fibronectin receptor binding domain; Try-Ile-Gly-Ser-Arg (YI GSR), from the laminin receptor binding domain, and Ala-Asp-Gly-Glu-Al a (ADGEA), from the collagen receptor binding domain, to evaluate thei r inhibitory effect on cell-mediated matrix attachment and vitreous co ntraction in vitro, and on cell-induced TRD in rabbit eyes in vivo. In direct immunofluorescent stain demonstrated both bovine retinal pigmen t epithelial (RPE) cells and rabbit dermal fibroblasts expressed the a lpha(2) beta(1), alpha(5) beta(1) and alpha(6) beta(1) integrins, the collagen, fibronectin, and laminin receptors, respectively. GRGDS exhi bited a broad spectrum of inhibitory activity on RPE cell attachment t o extracellular matrices. YIGSR specifically inhibited RPE cell attach ment to laminin, whereas ADGEA inhibited RPE cell attachment to collag en type I and IV. ADGEA inhibited RPE cell-induced vitreous contractio n in a dose-dependent manner, whereas GRGDS and YIGSR had no effect. A DGEA (1250 mu g/mL) delayed the development of TRD but did not prevent it. ADGEA was nontoxic to cells and retina, as demonstrated by cytoto xicity tests and histological examination, The synthetic peptide, ADGE A, and its analogs may be potential candidates for the treatment of ce ll-mediated collagenous contraction in the ocular tissues.