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TW Gardner, L DeMaio, JM Tarbell, DA AntonettiPenn State Retina Research Group; VEGF Increases Paracellular transport in Retinal Endothelial Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3297.
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Purpose: Vascular endothelial growth factor (VEGF) increases microvascular permeability in vivo and contributes to decreased blood-retinal and blood-brain barrier integrity in diseases such as diabetic retinopathy and brain glioma. However, the physical transport pathways by which water and solutes cross the endothelium in response to VEGF are not completely understood. Methods: We developed an in vitro system to record simultaneous, real-time measures of water and solute flux across cell monolayers. This study tested the hypothesis that VEGF increases convective transport of water and solutes through a single paracellular pathway across bovine retinal endothelial cell monolayers (BRECs). Results: VEGF (50 ng/ml) induced a 3.5-fold increase in both water (Jv) and 70 kDa dextran (Pe) transport after 120 min. However, VEGF did not alter the osmotic reflection coefficient (s) of BREC monolayers to dextran over the time course of the experiment. Conclusion: This observation suggests that water and dextran share common paracellular pathways across the endothelium and that VEGF increases the number of paracellular "pores" or the size of existing "pores". These conclusions are consistent with previously observed VEGF-induced alterations of tight junctions, such as occludin and ZO-1 phosphorylation, which may regulate the opening of paracellular "pores".
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