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Ryan Pelis, Miguel Coca-Prados; A Renal-Like Organic Anion Transport System in Ciliary Epithelium. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3026.
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The purpose was to determine if the ciliary body expresses organic anion transporters found in the renal proximal tubule and if the tissue supports active organic anion transport through the blood-aqueous barrier.
The freshly dissected bovine ciliary body was mounted in Ussing chambers for determination of unidirectional and net active transepithelial flux of para-aminohippurate (PAH), a well-known substrate of the renal organic anion transport system. Transepithelial PAH transport was assessed in the absence or presence of probenecid (0.1 mM), a well-established inhibitor of renal organic anion transport. Reverse transcription polymerase chain reaction and immunoblotting were used to look for expression of members of the renal organic anion secretory system in extracts of human ciliary body. The transporters examined were the organic anion transporters 1 (OAT1) and 3 (OAT3), the sodium dicarboxylate cotransporters 1 (NaDC1) and 3 (NaDC3), and the multidrug resistance-associated protein 4 (MRP4). The subcellular distribution of OAT1 and MRP4 in the human ciliary body was determined by immunohistochemistry.
Under control conditions the flux of PAH across the bovine ciliary body in Ussing chambers was significantly higher in the aqueous humor-to-blood direction versus the blood-to-aqueous humor direction, with a flux ratio of 5.65 ± 0.579 (n = 4, P<0.05, two-tailed t-test). In a separate set of experiments, probenecid significantly reduced the flux ratio from 5.36 ± 0.60 to 1.31 ± 0.27 (n = 4, P<0.05, two-tailed t-test). mRNA and protein (immunoblotting) corresponding to OAT1, OAT3, NaDC3 and MRP4, but not NaDC1, were detected in extracts of human ciliary body. The uptake transporter OAT1 localized to basolateral membranes of non-pigmented epithelial cells while the efflux transporter MRP4 localized to basolateral membranes of pigmented cells.
The ciliary body expresses many of the transporters involved in renal organic anion secretion. Like the renal tubule, the ciliary body supports probenecid-sensitive transepithelial transport of PAH, which is active and in the aqueous humor-to-blood direction. The subcellular expression of OAT1 and MRP4 in the human ciliary body is entirely consistent with the net direction of organic anion transport supported by this tissue.
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