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

• Published in: Molecular pharmaceutics 2013-02, Vol.10 (2), p.650-663
• Main Authors: Dahlin, Amber, Geier, Ethan, Stocker, Sophie L, Cropp, Cheryl D, Grigorenko, Elena, Bloomer, Michele, Siegenthaler, Julie, Xu, Lu, Basile, Anthony S, Tang-Liu, Diane D-S, Giacomini, Kathleen M
• Format: Article
• Language: English
• Subjects: Acyclovir - metabolism; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Cornea - metabolism; Eye - metabolism; Gene Expression Profiling - methods; Humans; Immunohistochemistry; In Vitro Techniques; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Organic Anion Transporters, ATP-Dependent - genetics; Organic Anion Transporters, ATP-Dependent - metabolism; Organic Anion Transporters, Sodium-Independent - genetics; Organic Anion Transporters, Sodium-Independent - metabolism; Real-Time Polymerase Chain Reaction; Retina - metabolism; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp300429e

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.