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Chun-hong Xia, Eric Lu, Xiaohua Gong; LRP5 Is a Potential Target for Anti-intraretinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3124.
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To understand the underlying mechanisms for the opposite retinal vasculature phenotypes in the loss-of-function mutant mice of low-density lipoprotein receptor-related protein 5 (LRP5) and very low-density lipoprotein receptor (VLDLR). To characterize the retinal vasculature defect in mice lacking both LRP5 and VLDLR.
Fundus examination, fluorescein angiography, immunostaining, and 3-dimensional retinal vasculature reconstruction were performed to evaluate the molecular and cellular alterations of retinal vasculature in mutant animals.
A loss of LRP5 in mice leads to an undergrowth of the intraretinal vasculature, the formation of endothelial cell (EC) clusters, and a failure of ECs to migrate into deeper retinal layers. In contrast, VLDLR knockout mice show an overgrowth of the intraretinal vasculature and subretinal neovascularization. Thus, LRP5 mediates a pro-angiogenic signal and VLDLR mediates an anti-angiogenic signal. Using the LRP5/VLDLR double knockout (DKO) mice, we have genetically tested whether a loss-of-function of LRP5 is able to prevent the neovascularization caused by VLDLR gene mutations. Our data reveal that retinal vessels fail to grow into the photoreceptor layer in the DKO mice.
LRP5 and VLDLR, members of the LDL receptor family, play opposite roles during retinal angiogensis. LRP5 is a prerequisite for the overgrowth of retinal vasculature in the VLDLR knockout mice. Thus, inhibition of LRP5 function is a potential novel approach to prevent intraretinal angiogenesis.
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