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B. Brankin, A.W. Stitt; Effects of Endostatin, Placental Growth Factor and Vascular Endothelial Growth Factor on Blood Retinal Barrier Function . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3913.
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Purpose: Breakdown of the inner blood retinal barrier (iBRB) is a major cause of visual loss in a number of ocular disorders. The endothelial cells of the iBRB contain tight junctions that confer highly selective properties of these vessels. The tight junctions contain several proteins including occludin and zonula occludens 1, 2 and 3. We determined the effects of endostatin, an endothelial-specific angiogenic inhibitor that inhibits ocular angiogenesis, placental growth factor (PLGF) and vascular endothelial growth factor (VEGF) on iBRB function Methods: Bovine retinal microvascular endothelial cells were exposed to endostatin (0-10ug/ml), VEGF (0-100ng/ml) or PLGF (0-100ng/ml) for 0-24h. Plasma membrane-enriched fractions were prepared from the retinal cell lysates and ZO-1 and occludin extracted and quantitated by western blotting and densitometric analyses. Tight junction phosphorylation status was determined by immunoprecipitation. Results: Endostatin caused a five-fold increase in occludin levels. Western blotting for endostatin-treated occludin showed three bands with molecular weights of 57, 62 and 78lDa. VEGF caused a 20% increase in ZO-1 levels. Endostatin and VEGF induced occludin phosphorylation on serine residues, but not tyrosine residues.VEGF caused a mobility shift for occludin from 60 to 62kDa molecular weight band. A 57kDa band was also present. PLGF induced phosphorylation of occludin on serine and tyrosine residues and did not significantly upregulate occludin levels. Conclusions: Endostatin, PLGF and VEGF may modify the capacity of occludin to associate with ZO-1 by inducing post-translational changes, and by altering the organisation of the tight junction proteins this may lead to breakdown of the endothelial permeability.
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