Michael W Stewart, MD
This brief talk described the structure of the blood-retinal barrier (BRB). The BRB is composed of the inner BRB and the outer BRB. The inner BRB is formed by the capillary endothelium and tight junctions between endothelial cells. The outer BRB is formed by a nearly impenetrable barrier between adjacent retinal pigment epithelial (RPE) cells and adjacent capillary endothelial cells. Occludin and claudins are proteins that bind the junctions at the molecular level, and control much of the barrier function. Under normal conditions, small hydrophobic and polar molecules pass freely through the tight junctions, but large polar molecules and anions require channels. Dr Stewart reminded the retinal specialists in attendance that permeability occurs transcellularly (through cell membranes of an individual cell) as well as paracellularly (through the junctions between cell membranes of adjacent cells).
Diabetes increases BRB permeability, which contributes to diabetic macular edema (DME). Retinal capillary leakage is most frequently implicated in the development of DME, but experimental and clinical studies show that diffuse RPE leakage also occurs in diabetes. Diabetes increases the amount of vascular endothelial growth factor (VEGF) in the eye, triggering 3 important changes in the tight junctions: phosphorylation of the tight junction proteins, reoganization of existing junctions from the plasma membrane to the cell cytoplasm, and decreasing the amount of junctional proteins.
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