ArticleInternational journal of pharmaceutics2013
Molecular expression and functional activity of efflux and influx transporters in hypoxia induced retinal pigment epithelial cells.
Article in International journal of pharmaceutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy.FEBS open bio · 2026Article
- Gene expression and DNA methylation changes in response to hypoxia in toxicant-adapted Atlantic killifish (Fundulus heteroclitus).Biology open · 2025Article
- Inhibition of KCTD10 Affects Diabetic Retinopathy Progression by Reducing VEGF and Affecting Angiogenesis.Genetics research · 2022Article
- Real-Time Monitoring the Effect of Cytopathic Hypoxia on Retinal Pigment Epithelial Barrier Functionality Using Electric Cell-Substrate Impedance Sensing (ECIS) Biosensor Technology.International journal of molecular sciences · 2021Article
- Hydrogen Sulfide: Novel Endogenous and Exogenous Modulator of Oxidative Stress in Retinal Degeneration Diseases.Molecules (Basel, Switzerland) · 2021Review
- β-elemene down-regulates HIF-lα, VEGF and iNOS in human retinal pigment epithelial cells under high glucose conditions.International journal of ophthalmology · 2020Article
- Roles of Drug Transporters in Blood-Retinal Barrier.Advances in experimental medicine and biology · 2019Review
- Multifunctional organic-inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery.International journal of nanomedicine · 2017Article
- Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy.Scientific reports · 2016Article
- Ritonavir inhibits HIF-1α-mediated VEGF expression in retinal pigment epithelial cells in vitro.Eye (London, England) · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A decrease in tissue oxygen levels (aka hypoxia) mediates a number of vascular retinal diseases. Despite introduction of novel therapeutics, treatment of retinal disorders remains challenging, possibly due to complex nature of hypoxia signaling. To date, the differential effect of hypoxia on expression of efflux and influx transporters in retinal cells has not been studied. Therefore, the objective of this study was to delineate molecular and functional expression of membrane transporters in human retinal pigment epithelial (RPE) cells cultured under normoxic and hypoxic conditions. Quantitative real time polymerase chain reaction (qPCR), ELISA and immunoblot analysis were performed to examine the RNA and protein expression levels of transporters. Further, functional activity was evaluated by performing the uptake of various substrates in both normoxic and hypoxic conditions. qPCR analysis showed elevated expression of efflux transporters (P-glycoprotein, multidrug resistant protein 2, breast cancer resistant protein) and influx transporters (folate receptor-α, cationic and neutral amino acid transporter, sodium dependent multivitamin transporter) in a time dependent manner. Immunoblot analysis further confirmed elevated expression of breast cancer resistant protein and sodium dependent multivitamin transporter. A decrease in the uptake of efflux transporter substrates (digoxin, lopinavir and abacavir) and enhanced uptake of influx transporter substrates (arginine, folic acid and biotin) in hypoxia relative to normoxia further confirmed elevated expression of transporters, respectively. This study demonstrates for the first time that hypoxic conditions may alter expression of efflux and influx transporters in RPE cells. These findings suggest that hypoxia may further alter disposition of ophthalmic drugs.
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