The purpose of the present study was to evaluate vitreous humor/retina-to-blood efflux transport in rats and determine the efflux transport of estradiol 17-β glucuronide (E17βG) across the blood-retinal barrier (BRB) by the use of microdialysis. [3H]E17βG and [14C]d-mannitol, which were used as a model compound for amphipathic organic anions and a bulk flow marker, respectively, were injected into the vitreous humor of rat eye, and a microdialysis probe was placed in the vitreous humor. [3H]E17βG and [14C]d-mannitol were bi-exponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [3H]E17βG during the terminal phase was 1.9-fold greater than that of [14C]d-mannitol and reduced the level of [14C]d-mannitol in the retinal presence of 0.3 mM E17βG, suggesting that [3H]E17βG is transported via a carrier-mediated efflux transport process across the BRB. The efflux transport of [3H]E17βG was significantly inhibited by organic anions, such as probenecid, sulfobromophthalein, digoxin, and dehydroepiandrosterone sulfate, whereas it was not inhibited by p-aminohippuric acid. In conclusion, the efflux transport of [3H]E17βG across the rat BRB was evaluated by microdialysis and its inhibition by organic anions suggests organic anion transporting polypeptide 1a4-mediated E17βG efflux transport at the BRB.
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