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J. Kim, J. Kim, Y. Lee, K.-W. Kim, Y. Yu; Decursin Inhibits VEGF-Mediated Inner Blood-Retinal Barrier Breakdown by Suppression of VEGFR-2 Activation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5098.
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The blood-retinal barrier (BRB) is essential for the normal structural and functional integrity of the retina, whose breakdown could cause the serious vision loss. Vascular endothelial growth factor (VEGF), as a permeable factor, induces alteration of tight junction proteins to result in BRB breakdown.
Using streptozotocin-induced diabetic mice and advanced glycation end product-treated human retinal microvascular endothelial cells (HRMECs), the effect of decursin on vascular permeability and tight junction protein expression was investigated through perfusion of retinal vessels with FITC-bovine serum albumin, [3H] sucrose permeability assay, cell viability assay, western blotting, immunocytochemistry, immunohistochemistry, and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay.
In retinal endothelial cells, decursin inhibited VEGF-mediated hyper-permeability. Decursin prevented VEGF-mediated loss of tight junction proteins including zonula occludens-1 (ZO-1), ZO-2 and occludin in retinal endothelial cells, which was also supported by restoration of tight junction proteins in intercellular junction. In addition, decursin significantly inhibited VEGF-mediated vascular leakage from retinal vessels, which was accompanied by prevention of loss of tight junction proteins in retinal vessels. Decursin significantly suppressed VEGF-induced VEGFR-2 phosphrylation which consequently led to inhibition of ERK 1/2 activation. Moreover, decursin induced no cytotoxicity to retinal endothelial cells and no retinal toxicity under therapeutic concentrations.
Our results suggest that decursin prevents VEGF-mediated BRB breakdown through blocking of loss of tight junction proteins, which might be regulated by suppression of VEGFR-2 activation. As a novel inhibitor to BRB breakdown, decursin could be applied to variable retinopathies with BRB breakdown.
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