Induction of differentiation by pyruvate and DMEM in the human retinal pigment epithelium cell line ARPE-19

Ahmado, Ahmad; Carr, Amanda-Jayne; Vugler, Anthony A.; Semo, Ma'ayan; Gias, Carlos; Lawrence, Jean M.; Chen, Li Li; Chen, Fred K.; Turowski, Patric; da Cruz, Lyndon; Coffey, Peter J.

doi:10.1167/iovs.10-6374

Cited by 100Retinal Diseases and TreatmentsRetinal Development and DisordersRetinal Imaging and Analysis

Induction of differentiation by pyruvate and DMEM in the human retinal pigment epithelium cell line ARPE-19

Ahmado, Ahmad, Carr, Amanda-Jayne, Vugler, Anthony A., Semo, Ma'ayan, Gias, Carlos, Lawrence, Jean M., Chen, Li Li, Chen, Fred K. +3 more·2011·Investigative Opthalmology & Visual Science

DOI 10.1167/iovs.10-6374

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Abstract

PURPOSE: Cultured retinal pigment epithelium (RPE) may become a therapeutic option for transplantation in retinal disease. However maintaining a native RPE phenotype in vitro has proven challenging. The human RPE cell-line ARPE-19 is used widely as an alternative to primary RPE. It is grown in DMEM/F12 medium as standard, but its phenotype is dependent on culture conditions, and many differentiation markers are usually absent. The purpose of this study was to examine how this sensitive phenotype of ARPE-19 can be modulated by growth media with or without the metabolite pyruvate to elucidate better RPE growth conditions. METHODS: ARPE-19 cells at passages p22 to p28 were cultured on filters for up to 3 months in DMEM/F12 or DMEM media with or without pyruvate and 1% fetal calf serum. Assessment of differentiation was performed using pigmentation, immunocytochemistry, protein/mRNA expression, transepithelial resistance, VEGF secretion, and ultrastructure. RESULTS: Pyruvate, in combination with DMEM, induced dark pigmentation and promoted differentiation markers such as CRALBP and MerTK. Importantly, RPE65 protein was detected by Western blotting and was enhanced by pyruvate, high glucose, and DMEM. ARPE-19 cells maintained in this medium could also phagocytose human photoreceptor outer segments (POS). VEGF secretion was greater in DMEM cultures and was affected by glucose but not by pyruvate. Pigmentation never occurred in DMEM/F12. CONCLUSIONS: This study demonstrated important differentiation markers, including pigmentation and Western blots of RPE65 protein, and showed human POS phagocytosis in ARPE-19 cultures using a simple differentiation protocol. The results favor the use of high-glucose DMEM with pyruvate for future RPE differentiation studies.

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Addition of pyruvate in high-glucose DMEM causes ARPE-19 cells to recapitulate key features of RPE cells including RPE-specific differentiation markers, polygonal morphology, polar expression of proteins, extensive microvilli, the ability to phagocytose, and secretion of VEGF.
“With the addition of pyruvate in high-glucose DMEM, it was shown that ARPE-19 cells recapitulated key features of RPE cells including RPE-specific differentiation markers, polygonal morphology, polar expression of proteins, extensive microvilli, the ability to phagocytose, and secretion of VEGF (Ahmado et al., 2011).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Ahmado et al., 2011

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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
Rapid and efficient directed differentiation of human pluripotent stem cells into retinal pigmented epithelium
Buchholz, D. E., Pennington, B. O., Croze, R. H., Hinman, C. R., Coffey, P. J., & Clegg, D. O. (2013) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0163 · Cited by 261 · see citing works
Self-citation
A new perspective on lipid research in age-related macular degeneration
van Leeuwen, E. M., Emri, E., Merle, B. M. J., Colijn, J. M., Kersten, E., Cougnard-Gregoire, A., Dammeier, S., Meester-Smoor, M., Pool, F. M., de Jong, E. K., et al. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.04.006 · Cited by 247 · see citing works
Understanding photoreceptor outer segment phagocytosis: use and utility of RPE cells in culture
Mazzoni, F., Safa, H., & Finnemann, S. C. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.01.010 · Cited by 221 · see citing works
Interactions of the choroid, Bruch's membrane, retinal pigment epithelium, and neurosensory retina collaborate to form the outer blood-retinal-barrier
Fields, M. A., Priore, L. V. D., Adelman, R. A., & Rizzolo, L. J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100803 · Cited by 172 · see citing works
Studying Neutrophil Function in vitro: Cell Models and Environmental Factors
Blanter, M., Gouwy, M., & Struyf, S. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s284941 · Cited by 152 · see citing works
Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells.
Samuel, W., Jaworski, C. J., Postnikova, O. A., Kutty, R. K., Duncan, T. E., Tan, L. X., Poliakov, E., Lakkaraju, A., & Redmond, T. M. (2017) · PubMed Central · Cited by 153 · see citing works
A novel Bruch's membrane-mimetic electrospun substrate scaffold for human retinal pigment epithelium cells
Xiang, P., Wu, K., Zhu, Y., Xiang, L., Li, C., Chen, D.-L., Chen, F., Xu, G., Wang, A., Li, M., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.08.040 · Cited by 143 · see citing works
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Autophagy in the eye: implications for ocular cell health.
Frost, L. S., Mitchell, C. H., & Boesze-Battaglia, K. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.04.010 · Cited by 134 · see citing works
Rapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide
Hazim, R. A., Volland, S., Yen, A., Burgess, B. L., & Williams, D. S. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2018.10.009 · Cited by 126 · see citing works
“Although the premelanosome marker, Pmel17, has been detected in ARPE-19 cells (Ahmado et al., 2011), images of normal RPE melanosomes have never been shown.”
Background
Plasma membrane protein polarity and trafficking in RPE cells: past, present and future
Lehmann, G. L., Benedicto, I., Philp, N. J., & Rodriguez-Boulan, E. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.04.021 · Cited by 122 · see citing works
Barrier properties of cultured retinal pigment epithelium
Rizzolo, L. J. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2013.12.018 · Cited by 121 · see citing works
Implications of melanin binding in ocular drug delivery
Rimpelä, A., Reinisalo, M., Hellinen, L., Grazhdankin, E., Kidron, H., Urtti, A. O., & del Amo, E. M. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.12.008 · Cited by 119 · see citing works
Phagocytosis-dependent ketogenesis in retinal pigment epithelium
Reyes-Reveles, J., Dhingra, A., Alexander, D., Bragin, A., Philp, N. J., & Boesze-Battaglia, K. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.770784 · Cited by 116 · see citing works
Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration
Bharti, K., den Hollander, A. I., Lakkaraju, A., Sinha, D., Williams, D. S., Finnemann, S. C., Rickman, C. B., Malek, G., & D'Amore, P. A. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2022.109170 · Cited by 92 · see citing works
Studying melanin and lipofuscin in RPE cell culture models
Boulton, M. E. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.01.016 · Cited by 92 · see citing works
Proline mediates metabolic communication between retinal pigment epithelial cells and the retina
Yam, M., Engel, A. L., Wang, Y., Zhu, S., Hauer, A., Zhang, R., Lohner, D., Huang, J., Dinterman, M., Zhao, C., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.007983 · Cited by 89 · see citing works
Retinal Pigmented Epithelial Cells Obtained from Human Induced Pluripotent Stem Cells Possess Functional Visual Cycle Enzymes in Vitro and in Vivo*
Maeda, T., Lee, M.-J., Palczewska, G., Marsili, S., Tesar, P., Palczewski, K., Takahashi, M., & Maeda, A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.518571 · Cited by 81 · see citing works
Retinal pigment epithelium (RPE) cytoskeleton in vivo and in vitro
Bonilha, V. L. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.09.015 · Cited by 52 · see citing works
Proinflammatory cytokines decrease the expression of genes critical for RPE function.
Kutty, R. K., Samuel, W., Boyce, K., Cherukuri, A., Duncan, T. E., Jaworski, C. J., Nagineni, C. N., & Redmond, T. M. (2016) · PubMed Central · Cited by 50 · see citing works
Protective Effects of Curcumin Ester Prodrug, Curcumin Diethyl Disuccinate against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells: Potential Therapeutic Avenues for Age-Related Macular Degeneration
Muangnoi, C., Sharif, U., Bhuket, P. R. N., Rojsitthisak, P., & Paraoan, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133367 · Cited by 50 · see citing works
Polygonatum sibiricum polysaccharide inhibits high glucose-induced oxidative stress, inflammatory response, and apoptosis in RPE cells
Wang, W., Li, S., & Song, M. (2021) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2021.1883061 · Cited by 42 · see citing works
Characterization of artificially re-pigmented ARPE-19 retinal pigment epithelial cell model
Hellinen, L., Hagström, M., Knuutila, H., Ruponen, M., Urtti, A. O., & Reinisalo, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-50324-8 · Cited by 41 · see citing works
Reassessing the suitability of ARPE-19 cells as a valid model of native RPE biology
Pfeffer, B. A., & Fliesler, S. J. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2022.109046 · Cited by 39 · see citing works
A Journey of Cytolethal Distending Toxins through Cell Membranes
Boesze‐Battaglia, K., Alexander, D., Dlakić, M., & Shenker, B. J. (2016) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2016.00081 · Cited by 36 · see citing works
Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression
Peng, S., Wang, S.-B., Singh, D., Zhao, P. Y., Davis, K., Chen, B., Adelman, R. A., & Rizzolo, L. J. (2016) · Experimental Eye Research · doi:10.1016/j.exer.2016.08.021 · Cited by 35 · see citing works
Retino-protective effect of Bucida buceras against oxidative stress induced by H2O2 in human retinal pigment epithelial cells line
Assanga, S. B. I., Luján, L. M. L., Ángulo, D. F., Gil-Salido, A. A., Lara-Espinoza, C., & Rubio-Pino, J. L. (2015) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-015-0765-6 · Cited by 33 · see citing works
Mislocalisation of BEST1 in iPSC-derived retinal pigment epithelial cells from a family with autosomal dominant vitreoretinochoroidopathy (ADVIRC)
Carter, D. A., Smart, M. J. K., Letton, W., Ramsden, C. M., Nommiste, B., Chen, L., Fynes, K., Muthiah, M. N., Goh, P. A., Lane, A., et al. (2016) · Scientific Reports · doi:10.1038/srep33792 · Cited by 33 · see citing works
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Retinal pigment epithelial cells as a therapeutic tool and target against retinopathies
Pavan, B., & Dalpiaz, A. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.06.009 · Cited by 32 · see citing works
Experimental Models to Study Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy
Datlibagi, A., Zein-El-Din, A., Frohly, M., Willermain, F., Delporte, C., & Motulsky, E. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054509 · Cited by 31 · see citing works
Injectable Hydrogel Based on Gellan Gum/Silk Sericin for Application as a Retinal Pigment Epithelium Cell Carrier
Kim, S. I., Jeon, G., Kim, S. E., Choe, S. H., Kim, S. J., Seo, J. S., Kang, T. W., Song, J. E., & Khang, G. (2022) · ACS Omega · doi:10.1021/acsomega.2c05113 · Cited by 28 · see citing works
The Apical Localization of Na+, K+-ATPase in Cultured Human Retinal Pigment Epithelial Cells Depends on Expression of the β2 Subunit
Lobato-Álvarez, J. A., Roldán, M. L., López-Murillo, T. D. C., González-Ramírez, R., Bonilla-Delgado, J., & Shoshani, L. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00450 · Cited by 27 · see citing works
Optimization of Storage Temperature for Cultured ARPE-19 Cells
Pasovic, L., Utheim, T. P., Corraya, R. M., Lyberg, T., Messelt, E. B., Aabel, P., Chen, D. F., Chen, X., & Eidet, J. R. (2013) · Journal of Ophthalmology · doi:10.1155/2013/216359 · Cited by 27 · see citing works
The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway
Eidet, J. R., Reppe, S., Pasovic, L., Olstad, O. K., Lyberg, T., Khan, A. Z., Fostad, I. G., Chen, D. F., & Utheim, T. P. (2016) · Scientific Reports · doi:10.1038/srep22671 · Cited by 26 · see citing works
A convenient protocol for establishing a human cell culture model of the outer retina.
Lynn, S. A., Keeling, E., Dewing, J. M., Johnston, D. A., Page, A. M., Cree, A. J., Tumbarello, D. A., Newman, T. A., Lotery, A. J., & Ratnayaka, J. A. (2018) · F1000Research · doi:10.12688/f1000research.15409.1 · Cited by 25 · see citing works
Ex-vivo models of the Retinal Pigment Epithelium (RPE) in long-term culture faithfully recapitulate key structural and physiological features of native RPE
Lynn, S. A., Ward, G., Keeling, E., Scott, J. A., Cree, A. J., Johnston, D. A., Page, A. M., Cuan‐Urquizo, E., Bhaskar, A., Grossel, M. C., et al. (2017) · Tissue and Cell · doi:10.1016/j.tice.2017.06.003 · Cited by 25 · see citing works
Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells
Schäfer, N., Wolf, H. N., Enzbrenner, A., Schikora, J., Reichenthaler, M., Enzmann, V., & Pauly, D. (2020) · Antioxidants · doi:10.3390/antiox9090793 · Cited by 24 · see citing works
Functional optimization of electric cell-substrate impedance sensing (ECIS) using human corneal epithelial cells
Ebrahim, A. S., Ebrahim, T., Kani, H., Ibrahim, A. S., Carion, T. W., & Berger, E. A. (2022) · Scientific Reports · doi:10.1038/s41598-022-18182-z · Cited by 24 · see citing works
Adhesive protein‐free synthetic hydrogels for retinal pigment epithelium cell culture with low ROS level
Chen, Y. M., Liu, Z. Q., Feng, Z. H., Xu, F., & Liu, J. K. (2013) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34904 · Cited by 24 · see citing works
Regulation of Vascular Endothelial Growth Factor Expression by Extra Domain B Segment of Fibronectin in Endothelial Cells
Chen, S., Chakrabarti, R., Keats, E. C., Chen, M., Chakrabarti, S., & Khan, Z. A. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-9766 · Cited by 24 · see citing works
A hypotonic gel-forming eye drop provides enhanced intraocular delivery of a kinase inhibitor with melanin-binding properties for sustained protection of retinal ganglion cells
Kim, Y. C., Hsueh, H. T., Shin, M. D., Berlinicke, C. A., Han, H., Anders, N. M., Hemingway, A., Leo, K. T., Chou, R. T., Kwon, H., et al. (2021) · Drug Delivery and Translational Research · doi:10.1007/s13346-021-00987-6 · Cited by 23 · see citing works
In situ cell surface proteomics reveals differentially expressed membrane proteins in retinal pigment epithelial cells during autoimmune uveitis
Uhl, P., Szober, C. M., Amann, B., Priglinger, C., Ueffing, M., Hauck, S. M., & Deeg, C. A. (2014) · Journal of Proteomics · doi:10.1016/j.jprot.2014.06.020 · Cited by 22 · see citing works
Phototoxicity of Indocyanine Green and Brilliant Blue G under Continuous Fluorescent Illumination on Cultured Human Retinal Pigment Epithelial Cells
Takayama, K., Sato, T., Karasawa, Y., Sato, S., Ito, M., & Takeuchi, M. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10754 · Cited by 22 · see citing works
Hyperthermia-induced upregulation of vascular endothelial growth factor in retinal pigment epithelial cells is regulated by mitogen-activated protein kinases
Faby, H., Hillenkamp, J., Roider, J. B., & Klettner, A. (2014) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-014-2750-z · Cited by 21 · see citing works
Oxidative Stress and Dysfunctional Intracellular Traffic Linked to an Unhealthy Diet Results in Impaired Cargo Transport in the Retinal Pigment Epithelium (RPE)
Keeling, E., Chatelet, D. S., Johnston, D. A., Page, A. M., Tumbarello, D. A., Lotery, A. J., & Ratnayaka, J. A. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800951 · Cited by 21 · see citing works
Relationship between aldose reductase enzyme and the signaling pathway of protein kinase C in an in vitro diabetic retinopathy model
Sarıkaya, M., Yazıhan, N., & Evcimen, N. D. (2019) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2019-0211 · Cited by 18 · see citing works
Regulation of retinal pigment epithelial cell phenotype by Annexin A8
Lueck, K., Carr, A. F., Stampoulis, D., Gerke, V., Rescher, U., Greenwood, J., & Moss, S. E. (2017) · Scientific Reports · doi:10.1038/s41598-017-03493-3 · Cited by 18 · see citing works
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Enhanced Functional Integration of Human Photoreceptor Precursors into Human and Rodent Retina in an Ex Vivo Retinal Explant Model System
Yanai, A., Laver, C., Gregory, C. Y., Liu, R. R., & Gregory-Evans, K. (2015) · Tissue Engineering Part A · doi:10.1089/ten.tea.2014.0669 · Cited by 18 · see citing works
A Novel Choroidal Endothelial Cell Line Has a Decreased Affinity for the Age-Related Macular Degeneration–Associated Complement Factor H Variant 402H
Loeven, M. A., van Gemst, J. J., Schophuizen, C. M. S., Tilakaratna, V., van den Heuvel, L. P., Day, A. J., Klevering, B. J., & van der Vlag, J. (2018) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.iovs-17-22893 · Cited by 17 · see citing works
Claudins regulate gene and protein expression of the retinal pigment epithelium independent of their association with tight junctions
Liu, F., Xu, T., Peng, S., Adelman, R. A., & Rizzolo, L. J. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.108157 · Cited by 17 · see citing works
Small Molecule Mediated Proliferation of Primary Retinal Pigment Epithelial Cells
Swoboda, J. G., Elliott, J., Deshmukh, V., de Lichtervelde, L., Shen, W., Tremblay, M. S., Peters, E. C., Cho, C. Y., Lü, B., Girman, S. V., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb4001712 · Cited by 17 · see citing works
The p38 MAPK NF-κB pathway, not the ERK pathway, is involved in exogenous HIV-1 Tat-induced apoptotic cell death in retinal pigment epithelial cells
Bai, L., Zhu, X., Ma, T., Wang, J., Wang, F., & Zhang, S. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.05.022 · Cited by 16 · see citing works
Model Systems for Studying Mechanisms of Ocular Toxoplasmosis
Smith, J. R., Ashander, L. M., Ma, Y., Rochet, E., & Furtado, J. M. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9857-9_17 · Cited by 16 · see citing works
Computational Model of Ca2+ Wave Propagation in Human Retinal Pigment Epithelial ARPE-19 Cells
Vainio, I., Khamidakh, A. E. A., Paci, M., Skottman, H., Juuti‐Uusitalo, K., Hyttinen, J., & Nymark, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128434 · Cited by 15 · see citing works
Annexin A8 regulates Wnt signaling to maintain the phenotypic plasticity of retinal pigment epithelial cells
Lueck, K., Carr, A. F., Yu, L., Greenwood, J., & Moss, S. E. (2020) · Scientific Reports · doi:10.1038/s41598-020-58296-w · Cited by 15 · see citing works
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Effects of E-Cigarette Refill Liquid Flavorings with and without Nicotine on Human Retinal Pigment Epithelial Cells: A Preliminary Study
Goenka, S., & Simon, S. R. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182111655 · Cited by 13 · see citing works
An in vitro protocol to study the effect of hyperglycemia on intracellular redox signaling in human retinal pigment epithelial (ARPE-19) cells
Shivarudrappa, A. H., Gopal, S. S., & Ponesakki, G. (2019) · Molecular Biology Reports · doi:10.1007/s11033-019-04597-x · Cited by 12 · see citing works
The versatile roles of retinal pigment epithelium in the pathophysiology of retinitis pigmentosa
Ghanawi, H., & Koch, S. (2025) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2025.101390 · Cited by 13 · see citing works
Ishophloroglucin A Ameliorates VEGF-Induced Epithelial-Mesenchymal Transition via VEGFR2 Pathway Inhibition in Microgravity-Stimulated Human Retinal Pigment Epithelial Cells
Son, M., Ryu, B., Je, J.-G., Jeon, Y., & Kim, D. Y. (2022) · Antioxidants · doi:10.3390/antiox11112212 · Cited by 11 · see citing works
Upregulation of GADD45α in light-damaged retinal pigment epithelial cells
Gao, M.-L., Deng, W.-L., Huang, N., Wang, Y.-Y., Lei, X.-L., Xu, Z.-Q., Hu, D.-N., Cai, J.-Q., Lü, F., & Jin, Z.-B. (2016) · Cell Death Discovery · doi:10.1038/cddiscovery.2016.13 · Cited by 11 · see citing works
Retinal Pigment Epithelium Cell Culture
Klettner, A. (2020) · Springer eBooks · doi:10.1007/978-3-030-28384-1_17 · Cited by 11 · see citing works
A Comprehensive Proteomic and Phosphoproteomic Analysis of Retinal Pigment Epithelium Reveals Multiple Pathway Alterations in Response to the Inflammatory Stimuli
Song, J., Han, D., Lee, H., Kim, D. J., Cho, J., Park, J., & Seok, S. H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093037 · Cited by 11 · see citing works
CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments
Yang, S., Fan, Y., Yang, M., Ni, H., Bu, W., Yin, H., Yang, J., Wang, W., Zhai, D., Wu, X., et al. (2024) · Advanced Science · doi:10.1002/advs.202404067 · Cited by 10 · see citing works
Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium
FROST, L. S., LOPES, V. S., STEFANO, F. P., BRAGIN, A., WILLIAMS, D. S., MITCHELL, C. H., & BOESZE-BATTAGLIA, K. (2013) · Visual Neuroscience · doi:10.1017/s0952523813000096 · Cited by 9 · see citing works
Cell sheet engineering platforms integrating antibacterial and thermo-responsive functionalities: Cu-nanoparticle-loaded P4VP brushes for retinal cell sheet harvesting
Cieślik, A., Shymborska, Y., Tymetska, S., Stetsyshyn, Y., Bernasik, A., Brzychczy‐Włoch, M., Drożdż, K., Szajna, K., Krok, F., Budkowski, A., et al. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.162985 · Cited by 9 · see citing works
Wnt/β-Catenin Signaling Pathway Is Necessary for the Specification but Not the Maintenance of the Mouse Retinal Pigment Epithelium
Kim, J.-M., Min, K. W., Kim, Y.-J., Smits, R., Basler, K., & Kim, J. W. (2023) · Molecules and Cells · doi:10.14348/molcells.2023.0029 · Cited by 9 · see citing works
Sigma-2 receptor modulator CT1812 alters key pathways and rescues retinal pigment epithelium (RPE) functional deficits associated with dry age-related macular degeneration (AMD)
Lizama, B. N., Keeling, E., Cho, E.-A., Malagise, E. M., Knezovich, N., Waybright, L., Watto, E., Look, G. C., Caro, V. D., Caggiano, A. O., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-87921-9 · Cited by 8 · see citing works
Spontaneous generation of a novel foetal human retinal pigment epithelium ( RPE ) cell line available for investigation on phagocytosis and morphogenesis
Shao, Z., Wang, H., Zhou, X., Guo, B., Gao, X., Xiao, Z., Liu, M., Sha, J., Jiang, C., Luo, Y., et al. (2017) · Cell Proliferation · doi:10.1111/cpr.12386 · Cited by 8 · see citing works
Mulberry Extract Mitigates Glucose‐Induced Oxidative Injury in Differentiated ARPE‐19 Cells by Enhancing Antioxidant Defense: Implications for Diabetic Retinopathy
Sukboon, P., Phumsuay, R., Promkum, C., Thiyajai, P., Sukprasansap, M., & Muangnoi, C. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.70180 · Cited by 7 · see citing works
The Effects of Prolonged Storage on ARPE-19 Cells Stored at Three Different Storage Temperatures
Islam, R., Corraya, R. M., Pasovic, L., Khan, A. Z., Aass, H. C. D., Eidet, J. R., & Utheim, T. P. (2020) · Molecules · doi:10.3390/molecules25245809 · Cited by 7 · see citing works
PDGF-D-induced immunoproteasome activation and cell-cell interactions
Zhang, J., Li, W., Xiong, Z., Zhu, J., Ren, X., Wang, S., Kuang, H., Lin, X., Mora, A., & Li, X. (2023) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2023.03.047 · Cited by 7 · see citing works
Improvement of Storage Medium for Cultured Human Retinal Pigment Epithelial Cells Using Factorial Design
Pasovic, L., Utheim, T. P., Reppe, S., Khan, A. Z., Jackson, C. J., Thiede, B., Berg, J. P., Messelt, E. B., & Eidet, J. R. (2018) · Scientific Reports · doi:10.1038/s41598-018-24121-8 · Cited by 7 · see citing works
Role of Autotaxin in High Glucose-Induced Human ARPE-19 Cells
Liu, Y., Yamagishi, R., Honjo, M., Kurano, M., Yatomi, Y., Igarashi, K., & Aihara, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169181 · Cited by 6 · see citing works
Quantitative action spectroscopy reveals ARPE19 sensitivity to ultraviolet radiation at 350 nm and 380 nm
Anderson, G., McLeod, A. R., Bagnaninchi, P., & Dhillon, B. (2022) · Scientific Reports · doi:10.1038/s41598-022-17251-7 · Cited by 6 · see citing works
Pathological vitreous causes cell line‐derived (but not donor‐derived) retinal pigment epithelial cells to display proliferative vitreoretinopathy‐like features in culture
Sharma, M., Tiwari, A., Sharma, S., Bansal, R., Gupta, V., Gupta, A., & Luthra‐Guptasarma, M. (2014) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.12307 · Cited by 6 · see citing works
Evaluation of mesenchymal stem cells as an in vitro model for inherited retinal diseases
Dodina, M., Gurtsieva, D., Karabelsky, A. V., & Minskaia, E. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1455140 · Cited by 5 · see citing works
Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells.
Liu, W., Mohan, S. P., Nareshkumar, R. N., Jaganathan, S. S., Wen, Y., Ramasubramanyan, S., & Irudayaraj, J. (2021) · PubMed Central · Cited by 5 · see citing works
Influence of Substrate Stiffness on iPSC-Derived Retinal Pigmented Epithelial Cells
Wendland, R. J., Tucker, B. A., & Worthington, K. S. (2024) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szae022 · Cited by 4 · see citing works
Cultured Human Retinal Pigment Epithelial (hRPE) Sheets: A Search for Suitable Storage Conditions
Khan, A. Z., Utheim, T. P., Reppe, S., Sandvik, L., Lyberg, T., Roald, B., Ibrahim, I. B., & Eidet, J. R. (2018) · Microscopy and Microanalysis · doi:10.1017/s1431927618000144 · Cited by 4 · see citing works
QMR® and Patient Blood-Derived Secretome Modulate RPE microRNA Networks Under Oxidative Stress
Alibrandi, S., Mordà, D., Scimone, C., D’Ascola, A., Aliquò, F., Pozzato, A., Scalinci, S. Z., D’Angelo, R., Sidoti, A., & Donato, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178614 · Cited by 3 · see citing works
New Developments in Retinal Cell Transplantation and the Impact of Stem Cells
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Influence Of Pyruvate And Sodium Bicarbonate On The Induction Of Pigmentation In Arising Retinal Pigmented Epithelial-19 Cells (Arpe-19)
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Self-citation
ARPE-19, A Human Retinal Pigment Epithelial Cell Line with Differentiated Properties
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Rapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide
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Authors: Ahmado, A., Carr, A.-J., Vugler, A. A., Semo, M., Gias, C., Lawrence, J. M., Chen, L. L., Chen, F. K., Turowski, P., da Cruz, L., & Coffey, P. J.
Affiliations: Moorfields Eye Hospital NHS Foundation Trust (GB)
From Departments of Ocular Biology and Therapeutics and
University College London (GB)
From Departments of Ocular Biology and Therapeutics and the 2Department of Vitreoretinal Surgery, Moorfields Eye Hospital, London, United Kingdom.
Corresponding author: Ahmado, Ahmad
Carr, Amanda-Jayne
Vugler, Anthony A.
Semo, Ma'ayan
Gias, Carlos
Lawrence, Jean M.
Chen, Li Li
Chen, Fred K.
Turowski, Patric
Coffey, Peter J.
ORCID: Ahmado, Ahmad
Carr, Amanda-Jayne
Semo, Ma'ayan
Lawrence, Jean M.
Chen, Li Li
Chen, Fred K.
Turowski, Patric
Coffey, Peter J.
Venue: Investigative Opthalmology & Visual Science
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Published: 2011-09-08
Volume: 52
Issue: 10
Pages: 7148
ISSN: 0146-0404 (ISSN-L)
1552-5783
DOI: 10.1167/iovs.10-6374
OpenAlex: W2077480943
Cited by: 100
References: 80
Citations by year: 2026: 2 · 2025: 10 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 8 · 2012: 3
FWCI: 5.99
Type: journal article
Language: en
Open access: closed
Locations: Investigative Ophthalmology & Visual Science (publishedVersion)
PubMed (publishedVersion)
UWA Profiles and Research Repository (UWA) (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Lincy Foundation
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords: retinal pigment epithelium, ARPE-19 cells, RPE differentiation, pyruvate, high glucose, RPE65, CRALBP, MERTK, pigmentation, photoreceptor outer segment phagocytosis, VEGF secretion, transepithelial electrical resistance
MeSH terms: c-Mer Tyrosine Kinase, Retinoid Isomerohydrolase, Carrier Proteins, Cell Differentiation, Cells, Cultured, Culture Media, Enzyme-Linked Immunosorbent Assay, Eye Proteins, Humans, Phagocytosis, Phenotype, Proto-Oncogene Proteins, Blotting, Western, Biomarkers, Fluorescent Antibody Technique, Indirect, Pyruvic Acid, cis-trans-Isomerases, Reverse Transcriptase Polymerase Chain Reaction, Receptor Protein-Tyrosine Kinases, Vascular Endothelial Growth Factor A, Retinal Pigment Epithelium

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Induction of differentiation by pyruvate and DMEM in the human retinal pigment epithelium cell line ARPE-19

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