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J.-K. Shen, B. Xie, M. Swain, T. Lauer, S. F. Hackett, Y. Sato, P. A. Campochiaro; Regulation of Retinal Neovascularization by Vasohibin-2. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5889.
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Vasohibin-1 is expressed in endothelial cells, upregulated in the retina by vascular endothelial growth factor (VEGF) and inhibits VEGF-induced neovascularization. Vasohibin-2 is a newly identified protein that has substantial homology to Vasohibin-1. In this study, we investigated the expression and effects of Vasohibin-2 in the eye.
Vasohibin2 mRNA was measured by real-time RT-PCR in retinas of control mice, mice with oxygen-induced ischemic retinopathy (OIR), rhodopsin promoter/VEGF transgenic mice, and double transgenic mice with doxycycline-inducible expression of VEGF in the retina (Tet/opsin/VEGF mice). Immunohistochemistry for Vasohibin-2 was done in mice with OIR. The effect of intraocular injection of recombinant Vasohibin-2 protein or an adenoviral vector expressing Vasohibin-2 (AdVasohibin2) was tested in mice with OIR or mice with laser-induced choroidal neovascularization (CNV).
In ischemic retinas and retinas of Tet/opsin/VEGF mice, increased expression of VEGF was accompanied by elevation of vasohibin mRNA. Immunohistochemical staining for Vasohibin-2 was minimal in normal retina, but there was prominent staining in ischemic retina that co-localized with PECAM-1 indicating that it was in endothelial cells. Staining for Vasohibin-2 was particularly strong in regressing hyaloids vessels or regressing retinal neovascularization. Intraocular injection of recombinant Vasohibin-2 or AdVasohibin2 inhibited the development of retinal neovascularization in ischemic retinas, reduced CNV at rupture sites in Bruch’s membrane, and reduced neovascularization and retinal detachment in doxycycline-treated Tet/opsin/VEGF mice.
Vasohibin-2, like Vasohibin-1, participates in a VEGF negative feedback loop and suppresses neovascularization in the retina and choroid.
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