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L. Wu, J. Cai, S. Li Calzi, L. Shaw, M. Grant, M. Boulton; Placenta Growth Factor (PlGF) Can Antagonize VEGF-Induced Retinal Vascular Permeability. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2932.
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The aim of this study was to determine the effect of PlGF on VEGF-induced retinal microvascular permeability using both in vitro and in vivo models.
Bovine retinal microvascular endothelial cells (RMECs) were grown to confluence on culture inserts and maintained until they attained a transepithelial resistance of greater than 20 Ω.cm2. Cells were pretreated with VEGF (100ng/ml) for 24 hours and then exposed to (100ng/ml) PlGF for up to 24 hours and compared with cells plus PlGF or VEGF alone or no growth factor for the same time period. Changes in permeability were determined by measuring transendothelial electrical resistance (TER) and the flux of FITC-dextran (40 kDa) across the monolayer. For in vivo experiments, C57BL/6J mice (6-8 weeks old) received intravitreal injection with 1 µl VEGF and/or PlGF (10-6 M). Six hours later FITC-albumin was given by intravenous injection and the animals were sacrificed 2 hours later. Quantification of retinal capillary permeability under the different conditions was achieved by measuring the fluorescent intensity in the homogenized retinal samples from the mice.
PlGF produced a progressive and significant increase in TER and a decrease in the flux of fluorescent dextran at 24hr compared to untreated cells. By contrast, VEGF resulted in a significant reduction in TER and increase in the flux of fluorescent dextran compared to control. However, a combination of PlGF plus VEGF significantly inhibited the VEGF-induced reduction in TER (VEGF 9.68±1.801 vs VEGF+PlGF 28.05±1.934 Ω.cm2) and decreased flux of fluorescent dextran by 5-fold. In the in vivo experiments, intravitreal injection of VEGF induced a significant 40% increase in retinal capillary permeability compared with the vehicle control group. By contrast, PlGF alone tended to reduce permeability. Co-intravitreal injection of both PlGF and VEGF significantly reduced the leakage of fluorescent albumin by 80% compared to VEGF alone.
The results from this study indicate that PlGF can increase transepithelial resistance and is able to antagonize VEGF-induced retinal microvascular endothelial permeability. This reinforces the importance of VEGFR-1, the receptor for PlGF, as a key component in the regulation of vascular permeability.
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