title: Gene expression profiling of transporters in the solute carrier and ATP-binding cassette superfamilies in human eye substructures.
abstract: 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.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94158, United States.
authors.forename: Amber
authors.initials: A
authors.lastname: Dahlin
authors.forename: Ethan
authors.initials: E
authors.lastname: Geier
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Stocker
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Cropp
authors.forename: Elena
authors.initials: E
authors.lastname: Grigorenko
authors.forename: Michele
authors.initials: M
authors.lastname: Bloomer
authors.forename: Julie
authors.initials: J
authors.lastname: Siegenthaler
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Basile
authors.forename: Diane D-S
authors.initials: DD
authors.lastname: Tang-Liu
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Giacomini
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000212:Acyclovir / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D029365:Organic Anion Transporters, ATP-Dependent / Q000235:genetics / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D029365:Organic Anion Transporters, ATP-Dependent; D029362:Organic Anion Transporters, Sodium-Independent; C490280:SLC22A7 protein, human; D000212:Acyclovir