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Deepti Navaratna, PhD; Joann Maestas, MS; Paul G. McGuire, PhD; Arup Das, MD, PhD

Arch Ophthalmol. 2008;126(8):1082-1088.

Objectives  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.

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

Clinical Relevance  Inhibition of VE-cadherin might be an effective strategy for pharmacological inhibition in proliferative retinopathies.

Author Affiliations: Department of Cell Biology and Physiology (Drs Navaratna, McGuire, and Das and Ms Maestas) and Division of Ophthalmology, Department of Surgery (Drs McGuire and Das), University of New Mexico Health Sciences Center, and New Mexico VA Health Care System (Dr Das), Albuquerque.

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