Effects of diabetic retinopathy on the barrier functions of the retinal pigment epithelium

Diabetic retinopathy is a debilitating microvascular complication of diabetes mellitus. A rich literature describes the breakdown of retinal endothelial cells and the inner blood-retinal barrier, but the effects of diabetes on the retinal pigment epithelium (RPE) has received much less attention. RPE lies between the choroid and neurosensory retina to form the outer blood-retinal barrier. RPE's specialized and dynamic barrier functions are crucial for maintaining retinal health. RPE barrier functions include a collection of interrelated structures and activities that regulate the transepithelial movement of solutes, including: diffusion through the paracellular spaces, facilitated diffusion through the cells, active transport, receptor-mediated and bulk phase transcytosis, and metabolic processing of solutes in transit. In the later stages of diabetic retinopathy, the tight junctions that regulate the paracellular space begin to disassemble, but there are earlier effects on the other aspects of RPE barrier function, particularly active transport and metabolic processing. With advanced understanding of RPE-specific barrier functions, and more in vivo-like culture models, the time is ripe for revisiting experiments in the literature to resolve controversies and extend our understanding of how diabetes affects the outer blood-retinal barrier.