Retinal vascular permeability in diabetes

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus, and despite many years of research it continues to be the major cause of blindness in adults. Understanding the molecular mechanisms by which transport across the inner Blood Retinal Barrier (iBRB) is regulated is a key step for the discovery of improved means to control vascular permeability and loss of vision in persons with DR. In this study, using Bovine Retinal Endothelial Cell (BREC) monolayers we measured hydraulic conductivity and diffusive as well as apparent (i.e. diffusive plus convective) permeabilities of TAMRA (467 Da), Dextran (70 kDa), and LDL (2,000 kDa). We did not observe any significant change in permeability to the 3 tracer molecules or the conductance of water after exposure to high glucose. The transport results are consistent with observed ZO-1 staining. On the other hand, vascular endothelial growth factor (VEGF) increased BREC permeability in normal and high glucose environments. This supports the existence of an indirect pathway by which iBRB permeability is increased in hyperglycemia in vivo. The up-regulation of VEGF in pericytes that in turn increases endothelial permeability.