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Research ArticleMinireview

Drug Transport by the Blood–Aqueous Humor Barrier of the Eye

Jonghwa Lee and Ryan M. Pelis
Drug Metabolism and Disposition October 2016, 44 (10) 1675-1681; DOI: https://doi.org/10.1124/dmd.116.069369
Jonghwa Lee
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
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Ryan M. Pelis
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
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Abstract

The ocular barriers (cornea, blood–retinal barrier, and blood–aqueous humor barrier) make treating eye diseases with therapeutic drugs challenging. The tight capillary endothelium of the iris and the ciliary body epithelium form the blood–aqueous humor barrier. The iris and ciliary body (iris-ciliary body) express a variety of drug transporters in the ATP-binding cassette and solute carrier (SLC) families. ATP-binding cassette family drug transporters that are present in the iris-ciliary body include P-glycoprotein, breast cancer resistance protein, and several multidrug resistance–associated proteins. SLC family drug transporters that are present in the iris-ciliary body include organic anion transporters, organic anion transporting polypeptides, bile acid transporters (apical sodium-dependent bile salt transporter and sodium taurocholate cotransporter), organic cation transporters (novel organic cation transporter and multidrug and toxin extrusion transporter) and peptide transporters. Freshly dissected iris-ciliary body preparations actively accumulate a variety of substrates of SLC drug transporters that are expressed in the tissue. The ciliary body in vitro supports active transport in the aqueous humor-to-blood direction of several substrates of organic anion transporters and multidrug resistance–associated proteins, consistent with the subcellular localization of these transporters in the ciliary body epithelium. In vivo data suggest that drug transporters in the iris-ciliary body reduce the permeation of drugs in the direction of blood-to-aqueous humor, thereby reducing ocular drug bioavailability, and are also involved in active drug elimination from the aqueous humor. An understanding of the influence on pharmacokinetics of drug transporters in the blood–aqueous humor barrier should help improve drug delivery and efficacy in the eye.

Footnotes

    • Received January 6, 2016.
    • Accepted February 18, 2016.
  • dx.doi.org/10.1124/dmd.116.069369.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 44 (10)
Drug Metabolism and Disposition
Vol. 44, Issue 10
1 Oct 2016
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Research ArticleMinireview

Drug Transport by the Blood–Aqueous Humor Barrier

Jonghwa Lee and Ryan M. Pelis
Drug Metabolism and Disposition October 1, 2016, 44 (10) 1675-1681; DOI: https://doi.org/10.1124/dmd.116.069369

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Research ArticleMinireview

Drug Transport by the Blood–Aqueous Humor Barrier

Jonghwa Lee and Ryan M. Pelis
Drug Metabolism and Disposition October 1, 2016, 44 (10) 1675-1681; DOI: https://doi.org/10.1124/dmd.116.069369
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  • Article
    • Abstract
    • Introduction
    • Drug Transporters
    • The Blood–Aqueous Humor Barrier
    • Expression of ABC Transporters in Iris-Ciliary Body
    • Expression of SLC Transporters in the Iris-Ciliary Body
    • In Vitro Evidence for Drug Transporter Activity in the Iris-Ciliary Body
    • In Vivo Evidence for Drug Transporter Function in the Eye
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