RT Journal Article
SR Electronic
T1 Expression of Efflux Transporters in Human Ocular Tissues
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1934
OP 1948
DO 10.1124/dmd.113.052704
VO 41
IS 11
A1 Peng Chen
A1 Hao Chen
A1 Xinjie Zang
A1 Min Chen
A1 Haoran Jiang
A1 Shasha Han
A1 Xianggen Wu
YR 2013
UL http://dmd.aspetjournals.org/content/41/11/1934.abstract
AB 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.