Study of cationic drug efflux across the blood-retinal barrier

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: Kubo Yoshiyuki 富山大学, 大学院医学薬学研究部(薬学), 准教授 (20377427)
• Co-Investigator(Renkei-kenkyūsha): HOSOYA Ken-ichi 富山大学, 大学院医学薬学研究部(薬学), 教授 (70301033) ; Nishi Tsuyoshi 大阪大学, 産業科学研究所, 准教授 (60403002)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 血液網膜関門 / トランスポーター / カチオン性薬物 / 神経保護薬

Outline of Final Research Achievements

In vivo transport study in rats suggested the facilitative transport systems for cationic compounds, such as clonidine, nicotine, riboflavin and L-ornithine at the blood-retinal barrier (BRB). In addition, in vitro transport study with TR-iBRB2 cells, an in vitro model cell line of the inner BRB, suggested the involvement of carrier-mediated process in these cationic drugs and compounds, showing the usefulness of clonidine transport system in systemic drug delivery to the retina. In vitro study of inhibition, vectorial transport and immunohistochemical analysis suggested the responsible contribution of cationic amino acid transporter 1 (CAT1/SLC7A1) to the blood-to-retina transport of L-ornithine at the inner and outer BRB. Knockdown study suggested the contribution of riboflavin transporter (RFVTs/SLC52A) to riboflavin transport at the inner BRB, and mRNA expression study supported that RFVT2 is dominant in the influx transport of riboflavin at the inner BRB.

Free Research Field

生物薬剤学