Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model.
Integrin alpha v beta 3 is differentially expressed in angiogenic blood vessels in skin granulation tissue, and alpha v beta 3 antagonists inhibit angiogenesis in chick chorioallantoic membranes. In this study, we investigated the role of alpha v beta 3 in retinal neovascularization. There was no detectable signal for alpha v beta 3 by immunohistochemistry in normal human retina, but neovascular tissue removed from the surface of the retina of patients with diabetic retinopathy showed intense staining for alpha v beta 3 within the endothelial cells of new blood vessels. In a murine model of oxygen-induced ischemic retinopathy, there was intense staining for alpha v beta 3 in endothelial cells participating in neovascularization but no detectable staining in normal retinal blood vessels of adult mice. Synthetic peptides that bind alpha v beta 3 and perturb alpha v beta 3-mediated adhesion in vitro inhibited retinal neovascularization in the murine model when given by intraperitoneal or periocular injections. These data suggest that alpha v beta 3 antagonists may provide a useful adjunct for the treatment of retinal neovascularization.
Luna
J
J
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Tobe
T
T
Mousa
S A
SA
Reilly
T M
TM
Campochiaro
P A
PA
D000818:Animals; D003930:Diabetic Retinopathy / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000502:physiology; D015861:Retinal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000737:chemistry; D015854:Up-Regulation
D009842:Oligopeptides; D010456:Peptides, Cyclic; D019030:Receptors, Vitronectin; C101857:XJ 735; C101858:XK 002