Attenuation of retinal vascular development and neovascularization in transgenic mice over-expressing thrombospondin-1 in the lens

Authors

  • Zhifeng Wu,

    1. Departments of Ophthalmology & Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin
    Current affiliation:
    1. Department of Ophthalmology, Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, China
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  • Shoujian Wang,

    1. Departments of Ophthalmology & Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin
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  • Christine M. Sorenson,

    1. Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin
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  • Nader Sheibani

    Corresponding author
    1. Departments of Ophthalmology & Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin
    2. Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin
    • University of Wisconsin Medical School, Department of Ophthalmology & Visual Sciences, 600 Highland Avenue, K6/458 CSC, Madison, WI 53792-4673
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Abstract

Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis and induces endothelial cell (EC) apoptosis. To study the role TSP1 plays during vascular development and neovascularization, we assessed the effects of ectopic TSP1 expression in the lens on retinal vascularization in transgenic mice. The TSP1 over-expressing mice showed abnormalities in the development of retinal vasculature. There was a dramatic decrease in the density of superficial and deep vascular plexuses of the retina in transgenic mice. The retinal vessels in TSP1 transgenic mice also appeared nonuniform and abnormal in maturation. We detected an increase in the number of EC undergoing apoptosis, which was compensated, in part, by an increase in cell proliferation in retinal vasculature of TSP1 transgenic mice. The TSP1 transgenic mice also exhibited increased levels of vessel obliteration and a limited preretinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Our results indicate increased expression of TSP1 attenuates normal retinal vascularization and preretinal neovascularization during OIR. Therefore, modulation of TSP1 expression may provide an effective mechanism for regulation of ocular angiogenesis. Developmental Dynamics 235:1908–1920, 2006. © 2006 Wiley-Liss, Inc.

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