Occludin phosphorylation and ubiquitination regulate tight junction trafficking and vascular endothelial growth factor-induced permeability.

Vascular endothelial growth factor (VEGF) alters tight junctions (TJs) and promotes vascular permeability in many retinal and brain diseases. However, the molecular mechanisms of barrier regulation are poorly understood. Here we demonstrate that occludin phosphorylation and ubiquitination regulate VEGF-induced TJ protein trafficking and concomitant vascular permeability.

Glucocorticoids induce transactivation of tight junction genes occludin and claudin-5 in retinal endothelial cells via a novel cis-element.

Tight junctions between vascular endothelial cells help to create the blood-brain and blood-retinal barriers. Breakdown of the retinal tight junction complex is problematic in several disease states including diabetic retinopathy. Glucocorticoids can restore and/or preserve the endothelial barrier to paracellular permeability, although the mechanism remains unclear.

VEGF activation of protein kinase C stimulates occludin phosphorylation and contributes to endothelial permeability.

Purpose: VEGF is a potent permeabilizing factor that contributes to the pathogenesis of diabetic retinopathy and brain tumors. VEGF-induced vascular permeability in vivo and in cell culture requires PKC activity, but the mechanism by which PKC regulates barrier properties remains unknown. This study was conducted to examine how VEGF and diabetes alter occludin phosphorylation and endothelial cell permeability.

Glucocorticoid regulation of endothelial cell tight junction gene expression: novel treatments for diabetic retinopathy.

Loss of blood-retinal barrier (BRB) integrity and vascular permeability characterizes diabetic retinopathy, and new therapies to reverse or prevent vascular permeability are needed to treat this debilitating disease. Glucocorticoids are currently under investigation for use as a local therapeutic treatment for diabetic retinopathy. This review examines the changes that occur to barrier properties in diabetic retinopathy and the potential to use glucocorticoids to restore vascular barrier properties in the retina.