Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor–type integrins inhibits retinal neovascularization
- 1 May 1996
- journal article
- Published by Springer Nature in Nature Medicine
- Vol. 2 (5), 529-533
- https://doi.org/10.1038/nm0596-529
Abstract
Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor-type integrins appears to be required for the survival and maturation of newly formed but not quiescent blood vessels in several vascular beds including the retina, blockade of this downstream adhesion receptor system was investigated. In a mouse model of hypoxia-induced retinal neovascularization twice daily administration of 1 to 20 mg cyclic alpha v-integrin antagonist peptide per kilogram of body weight reduced capillary proliferation in a dose-dependent fashion--maximum 76%--without obvious side effects. A cyclic control peptide displayed no inhibitory effect on neovascularization. These findings indicate that systemic application of vitronectin receptor antagonists appears to be clinically feasible and is efficient in preventing retinal neovascularization and superior to cytokine-blocking strategies.Keywords
This publication has 26 references indexed in Scilit:
- Approaches to studying cell adhesion molecules in angiogenesisTrends in Cell Biology, 1995
- Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal DisordersNew England Journal of Medicine, 1994
- Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vesselsCell, 1994
- Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinomaCell, 1994
- Ten-year Incidence of Visual Loss in a Diabetic PopulationOphthalmology, 1994
- Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutantNature, 1994
- Requirement of the integrin beta 3 subunit for carcinoma cell spreading or migration on vitronectin and fibrinogenThe Journal of cell biology, 1992
- Arg‐Gly‐Asp constrained within cyclic pentapoptides Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1FEBS Letters, 1991
- Neovascular growth factorsEye, 1991
- Photocoagulation Treatment of Proliferative Diabetic RetinopathyOphthalmology, 1981