A renal‐like organic anion transport system in the ciliary body epithelium of the eye (1064.16)

Abstract

The ciliary body epithelium (CE) is a bilayer consisting of a pigmented cell layer and a non‐pigmented cell layer, which together act as a physical barrier between the circulation and the eye interior. Previous studies show that clearance of organic anions from the eye is slowed by the well‐established organic anion transport inhibitor, probenecid. The purpose of this study was to determine the direction of organic anion transport across the CE and the transport proteins that may contribute. Paired unidirectional fluxes (aqueous humor‐to‐blood and blood‐to‐aqueous humor) and net flux (the difference between the unidirectional fluxes) of the organic anion para‐aminohippurate (PAH) across the freshly dissected rabbit CE was determined using Ussing chambers. RT‐PCR, immunoblotting and immunohistochemistry were used to examine organic anion transporter expression in the human eye. Net active PAH transport across the rabbit CE was in the aqueous humor‐to‐blood direction, with flux ratios of ~5. Probenecid (0.1 mM) inhibited net active PAH transport by reducing the unidirectional aqueous humor‐to‐blood flux. The organic anion transporters OAT1, OAT3, NaDC3 and MRP4 were detected in extracts of human ciliary body by RT‐PCR. The efflux transporter MRP4 was also detected in human ciliary body extracts by immunoblotting, where it localized to the basolateral membrane (blood‐facing side) of pigmented cells (determined by immunohistochemistry). These data suggest that the CE contains an organic anion transport system similar to that found in the renal proximal tubule. We speculate that this system is functionally similar in that it is involved in clearing potentially harmful endobiotic and xenobiotic organic anions from the eye interior. Supported by NSERC, NSHRF and CIHR.Grant Funding Source: Supported by NSERC, NSHRF and CIHR