d-Serine, a coagonist for N-methyl-d-aspartate-type glutamate receptors, which mediate visual signal transmission, is thought to be generated from l-serine via serine racemase in the retina. However, the source of l-serine and d-serine in the retina are yet to be determined. The purpose of the present study was to investigate the characteristics of the blood-to-retina transport of serine at the inner blood-retinal barrier (BRB). In vivo study revealed the blood-to-retina transport of [3H]l-serine with an influx clearance of 49.9 μL/(min·g retina), which is greater than that of [3H]d-serine. This was consistent with the L-isomer-predominant uptake of serine by conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), an in vitro inner BRB model. [3H]l-Serine and [3H]d-serine uptake by TR-iBRB2 cells took place in an Na+-dependent and a concentration-dependent manner with Michaelis constant values of 97.5μM and 9.63mM, respectively. The uptake process of [3H]l-serine and [3H]d-serine was significantly inhibited by system ASC (alanine-serine-cysteine) substrates. Polymerase chain reaction analysis and immunocytochemistry revealed the expression of ASC transporters ASCT1 and ASCT2 in TR-iBRB2 cells. These results suggest that the system ASC at the inner BRB is a potent pathway for supplying serine in the form of the l-isomer from the circulating blood to the retina.
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