Suppression of retinal neovascularization with an antagonist to vascular endothelial cadherin.
OBJECTIVE
To examine the role of vascular endothelial cadherin (VE-cadherin) in cellular processes underlying angiogenesis and the effects of VE-cadherin inhibition on retinal angiogenesis.


METHODS
Retinal neovascularization was induced in newborn mice by exposure to 75% oxygen (postnatal days 7-12) followed by room air and quantitated from histological sections. Mice received daily intraperitoneal injections of either a VE-cadherin antagonist or a control peptide from postnatal days 12 to 17. In vitro cell migration, proliferation, and tubule formation were examined in the presence of the VE-cadherin antagonist. The effect of antagonist treatment on the integrity of established cell junctions was examined by fluorescein isothiocyanate-dextran monolayer permeability and VE-cadherin immunocytochemistry.


RESULTS
Treatment with the VE-cadherin antagonist significantly reduced retinal angiogenesis. Inhibition of VE-cadherin function suppressed tubule formation in endothelial cells. The antagonist treatment also decreased cell migration and proliferation. The antagonist treatment did not affect the integrity of existing cell junctions. Immunostaining for VE-cadherin and rates of monolayer permeability were comparable to those in untreated controls.


CONCLUSIONS
Our study points to a pivotal role played by VE-cadherin in the angiogenic process.


CONCLUSIONS
Inhibition of VE-cadherin might be an effective strategy for pharmacological inhibition in proliferative retinopathies.
Navaratna
Deepti
D
Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM 87131-0001, USA.
Maestas
Joann
J
McGuire
Paul G
PG
Das
Arup
A
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD; D015820:Cadherins / Q000037:antagonists & inhibitors*; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003911:Dextrans / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D015861:Retinal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000166:cytology; D000099152:Cadherin 5
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D015820:Cadherins; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D009842:Oligopeptides; D010456:Peptides, Cyclic; D000099152:Cadherin 5; C530939:Ac-CDAEC-NH2; C015219:fluorescein isothiocyanate dextran