Blood-to-retina transport of riboflavin via RFVTs at the inner blood-retinal barrier |
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| Affiliation: | 1. Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;2. School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Research Institute, Trinity College Dublin, Dublin 2, Ireland;1. TOS Department, Ural Federal University named after the First President of Russia B.N. Yeltsin, 19 Mira Str., 620002 Yekaterinburg, Russia;2. I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, 20 S. Kovalevskaya Str., 620990 Yekaterinburg, Russia;1. Laboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan;2. Laboratory of Medicinal Chemistry, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan;3. Laboratory of Clinical Pharmaceutics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan |
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| 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 Km of 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. |
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| Keywords: | Riboflavin Inner blood-retinal barrier Riboflavin transporter RFVT |
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