Ion channels and transporters of the retinal pigment epithelium

Reichhart, Nadine; Strauß, Olaf

doi:10.1016/j.exer.2014.05.005

Cited by 64 publications

(56 citation statements)

References 124 publications

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“…Like photoreceptors, the protein expression of Cav1.3 is under circadian control in the RPE (Genewsky et al., ; Muller, Mas Gomez, Ruth, & Strauss, ; Reichhart & Strauss, ). Interestingly, in Cav1.3 knockout mice, the RPE lacks peak phagocytic activity following morning photoreceptor shedding and retained a higher number of phagosomes at a later time of the day.…”

Section: The Relationship Between Retinal Photoreceptors and The Retimentioning

confidence: 99%

Circadian regulation in the retina: From molecules to network

2018

Eur J of Neuroscience

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The mammalian retina is the most unique tissue among those that display robust circadian/diurnal oscillations. The retina is not only a light sensing tissue that relays light information to the brain, it has its own circadian “system” independent from any influence from other circadian oscillators. While all retinal cells and retinal pigment epithelium (RPE) possess circadian oscillators, these oscillators integrate by means of neural synapses, electrical coupling (gap junctions), and released neurochemicals (such as dopamine, melatonin, adenosine, and ATP), so the whole retina functions as an integrated circadian system. Dysregulation of retinal clocks not only causes retinal or ocular diseases, it also impacts the circadian rhythm of the whole body, as the light information transmitted from the retina entrains the brain clock that governs the body circadian rhythms. In this review, how circadian oscillations in various retinal cells are integrated, and how retinal diseases affect daily rhythms.

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Section: The Relationship Between Retinal Photoreceptors and The Retimentioning

confidence: 99%

Circadian regulation in the retina: From molecules to network

2018

Eur J of Neuroscience

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“…Epithelial cells are polarized, i.e., there are different transporting molecules on both the apical and basolateral surfaces of the epithelial cells. There is a considerable number of different ion channels, transporters and pumps molecules that are present in epithelial cell membranes [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Measurement of Multi Ion Transport through Human Bronchial Epithelial Cell Line Provides an Insight into the Mechanism of Defective Water Transport in Cystic Fibrosis

et al. 2020

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We measured concentration changes of sodium, potassium, chloride ions, pH and the transepithelial potential difference by means of ion-selective electrodes, which were placed on both sides of a human bronchial epithelial 16HBE14σ cell line grown on a porous support in the presence of ion channel blockers. We found that, in the isosmotic transepithelial concentration gradient of either sodium or chloride ions, there is an electroneutral transport of the isosmotic solution of sodium chloride in both directions across the cell monolayer. The transepithelial potential difference is below 3 mV. Potassium and pH change plays a minor role in ion transport. Based on our measurements, we hypothesize that in a healthy bronchial epithelium, there is a dynamic balance between water absorption and secretion. Water absorption is caused by the action of two exchangers, Na/H and Cl/HCO3, secreting weakly dissociated carbonic acid in exchange for well dissociated NaCl and water. The water secretion phase is triggered by an apical low volume-dependent factor opening the Cystic Fibrosis Transmembrane Regulator CFTR channel and secreting anions that are accompanied by paracellular sodium and water transport.

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“…Another important protein for K þ concentration maintenance, Kir7.1, was apically enriched (Table 3), as indicated in the earlier literature. 36 Most of the detected proteins were expressed in a nonpolarized manner in hfRPE cells (Fig. 2C).…”

Section: Membrane Separation and Polarization Of The Cell Modelmentioning

confidence: 92%

“…33 In native human RPE, Na þ K þ ATPase is actually expressed on both cell surfaces. 36 Na þ K þ ATPase helps to maintain ideal ion concentration in the subretinal space, and it is vital for the functions of the RPE and photoreceptors. Another important protein for K þ concentration maintenance, Kir7.1, was apically enriched (Table 3), as indicated in the earlier literature.…”

Section: Membrane Separation and Polarization Of The Cell Modelmentioning

confidence: 99%

Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters

Hellinen

Sato

Reinisalo

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Retinal pigment epithelium (RPE) limits the xenobiotic entry from the systemic blood stream to the eye. RPE surface transporters can be important in ocular drug distribution, but it has been unclear whether they are expressed on the apical, basal, or both cellular surfaces. In this paper, we provide quantitative comparison of apical and basolateral RPE surface proteomes. METHODS. We separated the apical and basolateral membranes of differentiated human fetal RPE (hfRPE) cells by combining apical membrane peeling and sucrose density gradient centrifugation. The membrane fractions were analyzed with quantitative targeted absolute proteomics (QTAP) and sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) to reveal the membrane protein localization on the RPE cell surfaces. We quantitated 15 transporters in unfractionated RPE cells and scaled their expression to tissue level. RESULTS. Several proteins involved in visual cycle, cell adhesion, and ion and nutrient transport were expressed on the hfRPE plasma membranes. Most drug transporters showed similar abundance on both RPE surfaces, whereas large neutral amino acids transporter 1 (LAT1), pglycoprotein (P-gp), and monocarboxylate transporter 1 (MCT1) showed modest apical enrichment. Many solute carriers (SLC) that are potential prodrug targets were present on both cellular surfaces, whereas putative sodium-coupled neutral amino acid transporter 7 (SNAT7) and riboflavin transporter (RFT3) were enriched on the basolateral and sodium-and chloride-dependent neutral and basic amino acid transporter (ATB 0þ) on the apical membrane. CONCLUSIONS. Comprehensive quantitative information of the RPE surface proteomes was reported for the first time. The scientific community can use the data to further increase understanding of the RPE functions. In addition, we provide insights for transporter protein localization in the human RPE and the significance for ocular pharmacokinetics.

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Ion channels and transporters of the retinal pigment epithelium

Cited by 64 publications

References 124 publications

Circadian regulation in the retina: From molecules to network

Circadian regulation in the retina: From molecules to network

Measurement of Multi Ion Transport through Human Bronchial Epithelial Cell Line Provides an Insight into the Mechanism of Defective Water Transport in Cystic Fibrosis

Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters

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