April 1994
Volume 35, Issue 5
Free
Articles  |   April 1994
Nonpeptidic analogues of the Arg-Gly-Asp (RGD) sequence specifically inhibit the adhesion of human tenon's capsule fibroblasts to fibronectin.
Author Affiliations
  • R Hershkoviz
    Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • S Melamed
    Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • N Greenspoon
    Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • O Lider
    Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Investigative Ophthalmology & Visual Science April 1994, Vol.35, 2585-2591. doi:
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    • Get Citation

      R Hershkoviz, S Melamed, N Greenspoon, O Lider; Nonpeptidic analogues of the Arg-Gly-Asp (RGD) sequence specifically inhibit the adhesion of human tenon's capsule fibroblasts to fibronectin.. Invest. Ophthalmol. Vis. Sci. 1994;35(5):2585-2591.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

PURPOSE: Scar formation from the process of wound healing is mediated primarily by fibroblasts and is a major problem in ophthalmology in general and in glaucoma therapy in particular. Interactions between fibroblasts and glycoprotein components of the extracellular matrix (ECM) are among the major causes of scar formation. Recognition of ECM glycoproteins occurs via cell surface integrins that are specific for adhesion epitopes, such as the Arg-Gly-Asp (RGD-) containing amino acid sequence. The RGD sequence, which is present in several matrix and plasma proteins, including fibronectin (FN) and vitronectin, is involved in cell-ECM interactions that occur during inflammatory and homeostatic reactions. The present study was designed to examine the possibility of using RGD-mimetics as inhibitors of fibroblasts-FN interactions. METHODS: Two nonpeptidic mimetics of RGD were designed and constructed, and their inhibitory effect on the adhesion of human tenon's capsule fibroblasts to FN was examined. SF-6,5 consisting of the carboxylate group of Asp and the guanidinium group of Arg divided by a linear atom spacer and a newly designed mimetic, designated NS-11, were examined herein. RESULTS: The RGD mimetics, SF-6,5 and NS-11, but not an Arg-Gly-Glu (RGE) mimetic inhibited the adhesion of ocular fibroblasts to immobilized FN. SF-6,5 and NS-11 did not inhibit adhesion of the fibroblasts to laminin or spontaneous proliferation of fibroblasts. Trypsin pretreatment of the nonpeptidic RGD mimetics did not affect their ability to inhibit adhesion of the ocular fibroblasts to FN, whereas that of the RGD-containing peptide was abolished by the pretreatment. CONCLUSION: Nonpeptidic mimetics of RGD are attractive candidates for therapeutic agents to prevent the formation of scar tissue and related RGD-dependent pathologic events.

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