title: Blood-to-retina transport of riboflavin via RFVTs at the inner blood-retinal barrier.
abstract: Riboflavin (vitamin B2) supply to the retina across the inner blood-retinal barrier (BRB) was investigated. In rats, the apparent influx permeability clearance of [3H]riboflavin (62.8 μL/(min·g retina)) was much higher than that of a non-permeable paracellular marker, suggesting the facilitative influx transport of riboflavin across the BRB. The retinal uptake index (RUI) of [3H]riboflavin was 59.0%, and significantly reduced by flavin adenine dinucleotide (FAD), but not by l-ascorbic acid, suggesting the substrate specificity of riboflavin transport. TR-iBRB2 cells, an in vitro model of the inner BRB, showed a temperature- and concentration-dependent [3H]riboflavin uptake with a Kmof 113 nM, suggesting that the influx transport of riboflavin across the inner BRB involves a carrier-mediated process. [3H]Riboflavin uptake by TR-iBRB2 cells was slightly altered by Na+- and Cl--free buffers, suggesting that riboflavin transport at the inner BRB is preferentially Na+- and Cl--independent. [3H]Riboflavin uptake by TR-iBRB2 cells was significantly reduced by riboflavin analogues while the uptake remained unchanged by other vitamins. The function and inhibition profile suggested the involvement of riboflavin transporters (SLC52A/RFVT) in riboflavin transport at the inner BRB, and this is supported by expression and knockdown analysis of rRFVT2 (Slc52a2) and rRFVT3 (Slc52a3) in TR-iBRB2 cells.
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan. Electronic address: kuboyosh@pha.u-toyama.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Yahata
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miki
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Akanuma
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Hosoya
mesh_terms: D000818:Animals; D001692:Biological Transport; D001813:Blood-Retinal Barrier / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012256:Riboflavin / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D043562:Receptors, G-Protein-Coupled; C581655:SLC52A3 protein, rat; C000621938:Slc52a2 protein, rat; D012256:Riboflavin
keywords: Inner blood-retinal barrier; RFVT; Riboflavin; Riboflavin transporter; Vitamin B(2)