Blood-to-retina transport of riboflavin via RFVTs at the inner blood-retinal barrier. Issue 1 (February 2017)

• Record Type: Journal Article
• Authors: Kubo, Yoshiyuki; Yahata, Shizuka; Miki, Satoshi; Akanuma, Shin-ichi; Hosoya, Ken-ichi
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 32:Issue 1(2017)
• Page Start: 92
• Page End: 99
• Publication Date: 2017-02
• Subjects: Riboflavin -- Vitamin B2 -- Inner blood-retinal barrier -- Riboflavin transporter -- RFVT; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2016.09.006
• Languages: English
• ISSNs: 1347-4367

Abstract

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 [ 3 H]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 [ 3 H]riboflavin was 59.0%, and significantly reduced by flavin adenine dinucleotide (FAD), but not byl -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 [ 3 H]riboflavin uptake with a Km of 113 nM, suggesting that the influx transport of riboflavin across the inner BRB involves a carrier-mediated process. [ 3 H]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. [ 3 H]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. Graphical abstract: