Gene Expression Profiling of Transporters in the Solute Carrier and ATP-Binding Cassette Superfamilies in Human Eye Substructures

被引：49

作者：

Dahlin, Amber ^{[1
]}

Geier, Ethan ^{[1
]}

Stocker, Sophie L. ^{[1
]}

Cropp, Cheryl D. ^{[1
]}

Grigorenko, Elena ^{[2
]}

Bloomer, Michele ^{[3
]}

Siegenthaler, Julie ^{[4
]}

Xu, Lu ^{[1
]}

Basile, Anthony S. ^{[5
]}

Tang-Liu, Diane D-S. ^{[5
]}

Giacomini, Kathleen M. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA

[2] Life Technol, Woburn, MA USA

[3] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94158 USA

[4] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA

[5] Allergan Pharmaceut Inc, Irvine, CA USA

来源：

MOLECULAR PHARMACEUTICS | 2013年 / 10卷 / 02期

基金：

美国国家卫生研究院;

关键词：

expression profiling; open array; gene expression; eye; cornea; retina; protein expression; transporters; acyclovir; OAT2; BCRP; OCT3; ORGANIC ANION TRANSPORTER-2; BLOOD-RETINAL BARRIER; CATION TRANSPORTERS; P-GLYCOPROTEIN; DRUG EFFLUX; ABC TRANSPORTERS; MONOAMINE TRANSPORTER; SUBSTRATE-SPECIFICITY; MEMBRANE TRANSPORTERS; CORNEAL EPITHELIUM;

D O I：

10.1021/mp300429e

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The barrier epithelia of the cornea and retina control drug and nutrient access to various compartments of the human eye. While ocular transporters are likely to play a critical role in homeostasis and drug delivery, little is known about their expression, localization and function. In this study, the mRNA expression levels of 445 transporters, metabolic enzymes, transcription factors and nuclear receptors were profiled in five regions of the human eye: cornea, iris, ciliary body, choroid and retina. Through RNA expression profiling and immunohistochemistry, several transporters were identified as putative targets for drug transport in ocular tissues. Our analysis identified SLC22A7 (OAT2), a carrier for the antiviral drug acyclovir, in the corneal epithelium, in addition to ABCG2 (BCRP), an important xenobiotic efflux pump, in retinal nerve fibers and the retinal pigment epithelium. Collectively, our results provide an understanding of the transporters that serve to maintain ocular homeostasis and which may be potential targets for drug delivery to deep compartments of the eye.

引用

页码：650 / 663

页数：14

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