Inner Blood—Retinal Barrier: Transport Biology and Methodology

Abstract

Inner blood-retinal barrier (inner BRB) contains complex tight junctions of retinal capillary endothelial cells, limiting nonspecific transport between the circulating blood and the neural retina. Thus, understanding of inner BRB transport mechanisms is an important step toward drug targeting of the retina. Nevertheless, information of inner BRB transport is very limited due in part to the difficulty in precise determination of inner BRB transport properties. Although in vivo transport studies (e.g., retinal uptake index, RUI, method) have been performed to investigate solute transport into the retina, it is difficult to identify which substrates are taken up by the inner BRB versus other side of the retinal barrier (i.e., outer BRB which consists of retinal pigment epithelial cells). We recently developed various analytical methods that can be applied to in vitro, ex vivo, and in vivo settings, enabling to study mechanistically the influx and efflux via transporters and assess transporter gene levels at the inner BRB. Using a combination of newly developed and other conventional methods, we have elucidated various mechanisms as to how vitamin C, amino acids, creatine, and nucleosides are supplied to the retina and how organic anions are effluxed from the retina.