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.
Drug Metab Dispos. 2013 Nov;41(11):1934-48. doi: 10.1124/dmd.113.052704. Epub 2013 Aug 26.
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.
为了研究外排转运蛋白在人眼部组织中的表达谱，采用定量实时聚合酶链反应、Western 印迹和免疫组织化学方法，获得了人眼部组织中各种外排转运蛋白的相对 mRNA 和蛋白表达。检测了角膜、结膜、虹膜睫状体（ICB）、视网膜和脉络膜、人角膜上皮细胞系（HCEC）和人视网膜色素上皮细胞系（ARPE-19）中多药耐药相关蛋白 1-7（MRP1-7）、多药耐药蛋白 1（MDR1）P-糖蛋白、肺耐药蛋白（LRP）和乳腺癌耐药蛋白（BCRP）的表达。外排转运蛋白在眼部组织、HCEC 和 ARPE-19 中的表达部位和模式存在显著差异，并且在眼部组织中，mRNA 和蛋白水平的外排转运蛋白表达谱也存在差异。在蛋白水平，MRP1-7、MDR1 和 LRP 在角膜上皮细胞中表达；MRP1-7、MDR1、LRP 和 BCRP 在结膜上皮细胞中表达；MRP1-2、MRP6-7、MDR1 和 LRP 在 ICB 中表达；MRP1-3、MRP6-7、MDR1 和 LRP 在视网膜中表达；MRP1-3、MRP6-7、MDR1 和 LRP 在 HCEC 中表达；MRP7、MDR1、LRP 和 BCRP 在 ARPE-19 中表达。本研究对正常眼部组织和细胞系中外排转运蛋白进行了定量和系统的研究，为跨眼部组织转运体表达差异提供了证据，提示在更好地理解眼部药代动力学和药效学数据时，应考虑外排转运体表达的可变性。
