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Research ArticleArticle

Expression of Efflux Transporters in Human Ocular Tissues

Peng Chen, Hao Chen, Xinjie Zang, Min Chen, Haoran Jiang, Shasha Han and Xianggen Wu
Drug Metabolism and Disposition November 2013, 41 (11) 1934-1948; DOI: https://doi.org/10.1124/dmd.113.052704
Peng Chen
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China
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Hao Chen
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China
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Xinjie Zang
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China
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Min Chen
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China
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Haoran Jiang
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China
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Shasha Han
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China
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Xianggen Wu
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China
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Abstract

To investigate the expression profiles of efflux transporters in human ocular tissues, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to obtain the relative mRNA and protein expressions of various efflux transporters in human ocular tissues. The cornea, conjunctiva, iris-ciliary body (ICB), retina and choroid, human corneal epithelial cell line (HCEC), and human retinal pigment epithelial cell line (ARPE-19) were examined for the expressions of multidrug resistance–associated proteins 1–7 (MRP1–7), multidrug resistance 1 (MDR1) P-glycoprotein, lung resistance protein (LRP), and breast cancer–resistance protein (BCRP). The expression sites and patterns of efflux transporters were significantly different in ocular tissues, HCEC, and ARPE-19, as well as the expression profiles of efflux transporters in mRNA and protein levels in ocular tissues. At the protein level, MRP1-7, MDR1, and LRP were expressed in the corneal epithelium; MRP1-7, MDR1, LRP, and BCRP were expressed in the conjunctival epithelium; MRP1-2, MRP6-7, MDR1, and LRP were expressed in the ICB; MRP1-3, MRP6-7, MDR1, and LRP were expressed in the retina; MRP1-3, MRP6-7, MDR1, and LRP were expressed in the HCEC; and MRP7, MDR1, LRP, and BCRP were expressed in the ARPE-19. This quantitative and systematic study of efflux transporters in normal ocular tissues and cell lines provides evidence of cross-ocular tissue transporter expression differences, implying that efflux transporter expression variability should be taken into consideration for better understanding of ocular pharmacokinetic and pharmacodynamic data.

Footnotes

    • Received May 24, 2013.
    • Accepted August 26, 2013.
  • ↵1 Current affiliation: Department of Microbiology, Key Laboratory of Medicine and Biotechnology of Qingdao, Qingdao University Medical College.

  • This work was supported by the National Natural Science Foundation of China [Project Nos. 81000369 and 81271036]; the Young and Middle-Aged Scientists Research Awards Fund of Shangdong Province, China [Project No. BS2009SV053]; and the Science and Technology Foundation of Qingdao, Shandong Province, China [Project No. 13-1-4-177-jch].

  • This manuscript was previously presented: Chen P, Chen H, Zang X, Chen M, Jiang H, Han S, Wu X (2013) Expression of Efflux Transporters in Human Ocular Tissues. International Symposium on Ocular Pharmacology and Pharmaceutics; 2013 Mar 7–10; Paris, France.

  • None of the authors has a proprietary or commercial interest in any of the mentioned drugs or companies.

  • dx.doi.org/10.1124/dmd.113.052704.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 41 (11)
Drug Metabolism and Disposition
Vol. 41, Issue 11
1 Nov 2013
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Research ArticleArticle

Efflux Transporters in Human Ocular Tissues

Peng Chen, Hao Chen, Xinjie Zang, Min Chen, Haoran Jiang, Shasha Han and Xianggen Wu
Drug Metabolism and Disposition November 1, 2013, 41 (11) 1934-1948; DOI: https://doi.org/10.1124/dmd.113.052704

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Research ArticleArticle

Efflux Transporters in Human Ocular Tissues

Peng Chen, Hao Chen, Xinjie Zang, Min Chen, Haoran Jiang, Shasha Han and Xianggen Wu
Drug Metabolism and Disposition November 1, 2013, 41 (11) 1934-1948; DOI: https://doi.org/10.1124/dmd.113.052704
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