May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Regulation of Retinal Neovascularization by Vasohibin-2
Author Affiliations & Notes
  • J.-K. Shen
    Ophthalmology, Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • B. Xie
    Ophthalmology, Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • M. Swain
    Ophthalmology, Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • T. Lauer
    Ophthalmology, Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • S. F. Hackett
    Ophthalmology, Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • Y. Sato
    Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
  • P. A. Campochiaro
    Ophthalmology, Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  J. Shen, None; B. Xie, None; M. Swain, None; T. Lauer, None; S.F. Hackett, None; Y. Sato, None; P.A. Campochiaro, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5889. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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).

Results: : 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.

Conclusions: : Vasohibin-2, like Vasohibin-1, participates in a VEGF negative feedback loop and suppresses neovascularization in the retina and choroid.

Keywords: neovascularization • retinal neovascularization • age-related macular degeneration 
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