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Inhibition of cell-induced vitreous contraction by synthetic peptide derived from the collagen receptor binding sequence.
- Source :
-
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics [J Ocul Pharmacol Ther] 1996 Fall; Vol. 12 (3), pp. 353-61. - Publication Year :
- 1996
-
Abstract
- Cell-mediated tractional retinal detachment (TRD) is the end result of various intraocular proliferative disorders. Interactions between cells 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 (YIGSR), from the laminin receptor binding domain, and Ala-Asp-Gly-Glu-Ala (ADGEA), from the collagen receptor binding domain, to evaluate their inhibitory effect on cell-mediated matrix attachment and vitreous contraction in vitro, and on cell-induced TRD in rabbit eyes in vivo. Indirect immunofluorescent stain demonstrated both bovine retinal pigment epithelial (RPE) cells and rabbit dermal fibroblasts expressed the alpha 2 beta 1, alpha 5 beta 1 and alpha 6 beta 1 integrins, the collagen, fibronectin, and laminin receptors, respectively. GRGDS exhibited a broad spectrum of inhibitory activity on RPE cell attachment to extracellular matrices. YIGSR specifically inhibited RPE cell attachment to laminin, whereas ADGEA inhibited RPE cell attachment to collagen type I and IV. ADGEA inhibited RPE cell-induced vitreous contraction in a dose-dependent manner, whereas GRGDS and YIGSR had no effect. ADGEA (1250 micrograms/mL) delayed the development of TRD but did not prevent it. ADGEA was nontoxic to cells and retina, as demonstrated by cytotoxicity tests and histological examination. The synthetic peptide, ADGEA, and its analogs may be potential candidates for the treatment of cell-mediated collagenous contraction in the ocular tissues.
- Subjects :
- Animals
Cattle
Cell Adhesion drug effects
Cells, Cultured
Collagen metabolism
Dose-Response Relationship, Drug
Extracellular Matrix metabolism
Extracellular Matrix Proteins metabolism
Fibroblasts cytology
Fibroblasts metabolism
Fluorescent Antibody Technique, Indirect
Oligopeptides chemical synthesis
Pigment Epithelium of Eye cytology
Rabbits
Receptors, Collagen
Retinal Detachment drug therapy
Retinal Detachment metabolism
Skin cytology
Vitreous Body drug effects
Integrins metabolism
Oligopeptides pharmacology
Pigment Epithelium of Eye metabolism
Skin metabolism
Vitreous Body physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1080-7683
- Volume :
- 12
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 8875342
- Full Text :
- https://doi.org/10.1089/jop.1996.12.353