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P. G. McGuire, D. Navaratna, G. Menicucci, D. Wilging, A. Das; Inhibition of VE-Cadherin Suppresses Retinal Angiogenesis in a Model of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3415.
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Angiogenesis is a multi-step process involving proliferation of endothelial cells followed by migration, tubule formation and vessel maturation. Endothelial junctional proteins play an important role in this process and must be engaged in stabilizing pre-tubule muticellular endothelial structures prior to lumen formation. The purpose of this study was to examine the role of VE-cadherin during retinal angiogenesis and whether this protein might be a suitable target for angiogenesis inhibition.
Retinal neovascularization was induced in newborn mice by exposure to 75% oxygen followed by room air. Mice received daily intraperitoneal injections of either a VE-cadherin antagonist (100mg/kg, Adherex Technologies Inc.) or a control peptide (100 mg/kg) from day 12 (start of hypoxia) to day 17 (angiogenic peak). Mice were treated with the antagonist between 16 mg/kg and 100 mg/kg to establish a dose response. To determine a more specific role for VE-cadherin in the angiogenic process, cultured bovine retinal microvascular endothelial cells were treated with or without the antagonist (1mg/ml) and examined for proliferation, migration and the formation of tubules in 3-dimensional gels.
The VE-cadherin antagonist was able to successfully suppress the appearance of neovascular tufts in mice with oxygen-induced retinopathy by 65%. The abundance of new vessels in the control peptide injected mice was comparable to non-injected mice. In the in-vitro assays, endothelial cells failed to form muticellular structures and tubules in presence of the VE-cadherin antagonist.
These observations point to a central role for VE-cadherin in the angiogenic process, specifically during tubule formation and in the assembly of mature new vessels. These results suggest that inhibition of VE-cadherin might be a viable target for anti-angiogenic therapies in late proliferative retinopathy.
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