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E. Cheung, K. Myers, G. D. Yancopoulos, I. B. Lobov, S. J. Wiegand; Placental Growth Factor (PlGF) Deficient Mice Show Delays in Normal Retinal Vascular Development and Reduced Vascular Abnormalities in Oxygen-Induced Retinal Ischemia. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2943.
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Several genes, such as VEGF-A, Dll4 and PDGF-B, play essential roles in both normal and pathological angiogenesis. Placental Growth Factor (PlGF), a member of the Vascular Endothelial Growth Factor (VEGF) family, shares many biochemical and molecular characteristics with VEGF-A, and is believed to function in concert with VEGF through its activation of VEGF Receptor 1 (Flt-1). PlGF has been linked to tumor angiogenesis, as well as ischemia and wound healing [Luttun et al., Nature Med. 2002, 8:831-840]. The purpose of the present study was to evaluate the effects of PlGF gene deletion on normal retinal vascular development, and on vasoobilteration and neovascularization in the murine model of oxygen-induced ischemic retinopathy (OIR).
The coding region of the PlGF gene was replaced with the β-galactosidase reporter gene. Mice heterozygous for the PlGF gene deletion were bred to generate litters containing PlGF null, heterozygous, wild-type mice. Retinas were collected at P6, flatmounted and stained with FITC-labeled Griffonia simplicfolia (GS) lectin I. For the OIR model, litters were place in a 75% O2 environment at day 7 after birth (P7) and returned to room air at P12. Retinas were collected at P12 and P17, flatmounted and stained with GS lectin I and an antibody against NG2, a mural cell marker.
In the developing superficial retinal vasculature, PlGF was most prominently expressed in the endothelium of arteries and growing capillary sprouts. At P6, the retinal vasculature in PlGF knockout mice exhibited a less complete coverage of the retina, suggesting a reduced rate of retinal vessel outgrowth, but increased retinal capillary density compared to wild-type littermates. In OIR, PlGF null mice showed a decreased vasoobliteration at P12, and at P17 exhibited a decrease in pathological neovascularization. Mice heterozygous for PlGF deletion exhibited an intermediate phenotype.
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