Involvement of OCTN2 in the transport of acetyl-lcarnitine across the inner blood-retinal barrier

Masanori Tachikawa, Yoko Takeda, Masatoshi Tomi, Ken ichi Hosoya

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

PURPOSE. To elucidate the mechanisms of acetyl-L-carnitine transport across the inner blood-retinal barrier (inner BRB). METHODS. In vivo integration plot and retinal uptake index (RUI) analyses were used to examine acetyl-L-[3H]carnitine transport in the retina across the inner BRB in rats. RUI was determined from the ratio of acetyl-L-[3H]carnitine and [14C]n-butanol, a freely diffusible internal reference, in the retina divided by the same ratio in the solution injected in the carotid artery. The transport mechanism was characterized in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), as an in vitro inner BRB model. RESULTS. The apparent influx permeability clearance (Kin) per gram retina of acetyl-L-[3H]carnitine was found to be 2.31 μL/(minute·g retina). The Kin of acetyl-L-[3H]carnitine was 3.7-fold greater than that of [3H]D-mannitol, a nonpermeable paracellular marker. Acetyl-L-[3H]carnitine uptake by the retina was found to be significantly inhibited by L-carnitine and acetyl- L-carnitine, supporting a carrier-mediated influx transport of acetyl-L-carnitine at the inner BRB. L-[3H]carnitine and acetyl-L- [3H]carnitine uptake by TR-iBRB2 cells was Na+- and concentration- dependent, with a Km of 29 and 26 μM, respectively. These forms of transport were significantly inhibited by organic cation/carnitine transporter (OCTN) substrates and inhibitors such as L-carnitine and acetyl-L-carnitine, tetraethylammonium, quinidine, and betaine. These transport properties are consistent with those of carnitine transport by OCTN2. OCTN2 was predominantly expressed in TR-iBRB2 cells and isolated rat retinal vascular endothelial cells. CONCLUSIONS. The findings suggest that OCTN2 is involved in the transport of acetyl-L-carnitine from the circulating blood to the retina across the inner BRB.

Original languageEnglish
Pages (from-to)430-436
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number1
DOIs
Publication statusPublished - 2010 Jan

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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