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.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics