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Masanori Tachikawa, Yoko Takeda, Masatoshi Tomi, Ken-ichi Hosoya; Involvement of OCTN2 in the Transport of Acetyl-l-Carnitine across the Inner Blood–Retinal Barrier. Invest. Ophthalmol. Vis. Sci. 2010;51(1):430-436. doi: 10.1167/iovs.09-4080.
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To elucidate the mechanisms of acetyl-l-carnitine transport across the inner blood–retinal barrier (inner BRB).
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.
The apparent influx permeability clearance (K in) per gram retina of acetyl-l-[3H]carnitine was found to be 2.31 μL/(minute · g retina). The K in 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 K m 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.
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.
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