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Y. Liu, J. Cao, Z. Li, I. B. Lobov, G. D. Yancopoulos, S. J. Wiegand; Placental Growth Factor (PlGF) Deficiency Reduces Pathological Angiogenesis in a Mouse Model of Matrigel Induced Choriodal Neovascularization (CNV). Invest. Ophthalmol. Vis. Sci. 2010;51(13):3356.
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Placental growth factor is structurally related to VEGF-A, and also a ligand for VEGF receptor-1 (Flt-1). PlGF acts synergistically with VEGF in a wide range of vascular pathologies (Carmeliet et al, Nat Med, 2001), including pathological angiogenesis in the eye (Rakic et al. IOVS 2003; 44:3186-93). The present study evaluated the effects of genetic deletion of PlGF on pathological angiogenesis in a mouse model of matrigel induced choriodal neovascularization (CNV).
PlGF null mice (-/-) in which a lacZ reporter gene was knocked into the PlGF coding region, and their wild type (+/+) littermates, aged 46 weeks, were employed in these studies. Expression of the LacZ reporter in retina and choroid was examined in cryo-sections and retinal flatmounts stained for beta-galactosidase activity. CNV was induced in PlGF null and control mice by subretinal injection of a 75% matrigel solution (0.5 µl). On day 35, the vasculature was labeled by perfusion of a DiI solution. Then the eyes were harvested and the lesion and CNV volumes were measured in cryostat-sections (12µm) cut through the entire extent of the lesion using fluorescence microscopy. Infiltration of leukocytes was evaluated in cross-sections stained with H&E staining or an antibody against the pan-leukocyte marker CD45.
LacZ staining demonstrated that PlGF was expressed in both retinal and choroidal vessels. The CNV neovessel volume was significantly decreased in PlGF KO mice, compared with WT controls (74% decrease in vessel volume, p<0.05). Leukocyte infiltration was also reduced in the lesions of PlGF KO mice, compared with the WT controls.
This study demonstrates that PlGF is expressed in the choroidal vasculature, and that genetic deletion of PlGF reduces matrigel induced CNV in mice. These results are consistent with observations in other disease models.
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