Blood-to-retina transport of creatine via creatine transporter (CRT) at the rat inner blood-retinal barrier

Toshihisa Nakashima, Masatoshi Tomi, Kazunori Katayama, Masanori Tachikawa, Masahiko Watanabe, Tetsuya Terasaki, Ken Ichi Hosoya

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


The purpose of this study was to elucidate the mechanisms of blood-to-retina creatine transport across the blood-retinal barrier (BRB) in vivo and in vitro, and to identify the responsible transporter(s). The creatine transport across the BRB in vivo and creatine uptake in an in vitro model of the inner BRB (TR-iBRB2 cells) were examined using [14C]creatine. Identification and localization of the creatine transporter (CRT) were carried out by RT-PCR, western blot, and immunoperoxidase electron microscopic analyses. An in vivo intravenous administration study suggested that [14C]creatine is transported from the blood to the retina against the creatine concentration gradient that exists between the retina and blood. [14C]Creatine uptake by TR-iBRB2 cells was saturable, Na+- and Cl --dependent and inhibited by CRT inhibitors, suggesting that CRT is involved in creatine transport at the inner BRB. RT-PCR and western blot analyses demonstrated that CRT is expressed in rat retina and TR-iBRB2 cells. Moreover, using an immunoperoxidase electron microscopic analysis, CRT immunoreactivity was found at both the luminal and abluminal membranes of the rat retinal capillary endothelial cells. In conclusion, CRT is expressed at the inner BRB and plays a role in blood-to-retina creatine transport across the inner BRB.

Original languageEnglish
Pages (from-to)1454-1461
Number of pages8
JournalJournal of Neurochemistry
Issue number6
Publication statusPublished - 2004 Jun 1
Externally publishedYes


  • Blood-retinal barrier
  • Carrier-mediated transport
  • Creatine
  • Creatine transporter
  • Retinal capillary endothelial cells

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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