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Rapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide
Open accessAbstract
Human RPE cell lines, especially the ARPE-19 cell line, are widely-used in eye research, as well as general epithelial cell studies. In comparison with primary RPE cells, they offer relative convenience and consistency, but cultures derived from these lines are typically not well differentiated. We describe a simple, rapid method to establish cultures from ARPE-19 cells, with significantly improved epithelial cell morphology and cytoskeletal organization, and RPE-related functions. We identify the presence of nicotinamide, a member of the vitamin B family, as an essential factor in promoting the observed differentiation, indicating the importance of metabolism in RPE cell differentiation.
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“However, these cell lines have genetic abnormalities, with triploidy in the D407 line (Davis et al., 1995), and an abnormal karyotype (most notably, a loss of one copy of chromosome 15, and an unbalanced translocation between the chromosome 15q and 19q) in the ARPE-19 line (Fasler-Kan et al., 2018; Hazim et al., 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Hazim et al., 2019
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“An important part of the protocol, reported by Hazim et al. for ARPE-19 cells, is a series of washes with trypsin that selectively removes the more proliferative cells, which tend to be more loosely adhered to the substrate, leaving behind firmly attached cells that more readily form a culture with a cobblestone appearance (Hazim et al., 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Hazim et al., 2019
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“These protocols required 3–4 months for RPE differentiation, whereas, a more recent protocol was able to achieve a similar level of differentiation within 4 weeks through the addition of nicotinamide instead of pyruvate (Hazim et al., 2019) (Fig. 5).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Hazim et al., 2019
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Cites
The Retinal Pigment Epithelium in Visual Function
Strauss, O. (2005) · Physiological Reviews · doi:10.1152/physrev.00021.2004 · Cited by 2,828 · cited 1×
“It performs specific functions in support of the photoreceptor cells, including the reisomerization of visual chromophore, and phagocytosis of photoreceptor outer segment (POS) membrane (Strauss, 2005).”
BackgroundComplement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449 · cited 5×
“The importance of the RPE for proper vision is underscored by several retinal degenerative diseases that involve RPE pathology, including age-related macular degeneration (AMD) (Bhutto and Lutty, 2012).”
BackgroundInfluentialComplement factor H variant increases the risk of age-related macular degeneration
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., et al. (2005) · Science · doi:10.1126/science.1110359 · Cited by 2,424 · cited 5×
“The importance of the RPE for proper vision is underscored by several retinal degenerative diseases that involve RPE pathology, including age-related macular degeneration (AMD) (Bhutto and Lutty, 2012).”
BackgroundInfluentialGomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482
ARPE-19, A Human Retinal Pigment Epithelial Cell Line with Differentiated Properties
Dunn, K. C., Aotaki-Keen, A. E., Putkey, F. R., & Hjelmeland, L. M. (1996) · Experimental Eye Research · doi:10.1006/exer.1996.0020 · Cited by 1,334 · cited 1×
“When first reported, standard cultures of the ARPE-19 cell line readily exhibited many of the characteristics of well-differentiated RPE cells, including cobblestone morphology, apical-basal polarity, and expression of RPE-specific proteins (Dunn et al., 1996).”
BackgroundCantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238 · cited 1×
“Nicotinamide has been shown to protect against oxidative stress and maintain mitochondrial health (Gomes et al., 2013; Mitchell et al., 2018), while its related compound, NR, was demonstrated to promote oxidative metabolism by means of increasing the NAD+/ NADH ratio (Canto et al., 2012).”
BackgroundBhutto, I. A., & Lutty, G. A. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.04.005 · Cited by 1,028 · cited 5×
“The importance of the RPE for proper vision is underscored by several retinal degenerative diseases that involve RPE pathology, including age-related macular degeneration (AMD) (Bhutto and Lutty, 2012).”
BackgroundInfluentialOrganization and execution of the epithelial polarity programme
Rodriguez-Boulan, E. J., & Macara, I. G. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3775 · Cited by 727 · cited 1×
“The cells typically exhibit incomplete execution of the epithelial polarity program (Rodriguez-Boulan and Macara, 2014), thus compromising their ability to represent in vivo biology.”
BackgroundStem cell metabolism in tissue development and aging
Shyh‐Chang, N., Daley, G. Q., & Cantley, L. C. (2013) · Development · doi:10.1242/dev.091777 · Cited by 602 · cited 1×
“Interestingly, many of the key enzymes and coenzymes in these metabolic pathways have been shown to become upregulated as cells differentiate into their terminal fate (Shyh-Chang et al., 2013; Hu et al., 2016).”
BackgroundRhyu, D. Y., Yang, Y., Ha, H., Lee, G. T., Song, J. S., Uh, S., & Lee, H. B. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2004050425 · Cited by 523 · cited 1×
“Interestingly, there is evidence to suggest that oxidative stress, and in particular reactive oxygen species, can promote epithelial-to-mesenchymal transition (Rhyu et al., 2005; Wang et al., 2010).”
Background
Cited by
Sorted by citations
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
“However, the morphological features of these cells do not appear as RPE-like as those reported by others (Ahmado et al., 2011; Hazim et al., 2019).”
BackgroundInfluentialRole of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium Dysfunction
Zhou, M., Geathers, J. S., Grillo, S. L., Weber, S. R., Wang, W., Zhao, Y., & Sundstrom, J. M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00501 · Cited by 199
Retinal pigment epithelium polarity in health and blinding diseases
Caceres, P. S., & Rodriguez-Boulan, E. J. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.08.001 · Cited by 105
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 98
Boles, N. C., Fernandes, M., Swigut, T., Srinivasan, R., Schiff, L., Rada-Iglesias, Á., Wang, Q., Saini, J. S., Kiehl, T. R., Stern, J. H., et al. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.03.009 · Cited by 81
“In addition, NAM improves cobblestone phenotype in immortalized ARPE19 cells (Hazim et al., 2019).”
BackgroundZou, H., Shan, C., Ma, L., Liu, J., Yang, N., & Zhao, J. (2020) · PeerJ · doi:10.7717/peerj.10136 · Cited by 59
“Due to the importance of TJs in the maintenance of integrity and functionality of epithelial cells, several researchers have focused on novel factors that stimulate the formation of TJs, such as nicotinamide (Hazim et al., 2019) and lysophosphatidic acid (Lidgerwood et al.”
BackgroundHazim, R. A., Paniagua, A. E., Tang, L., Yang, K., Kim, K. K. O., Stiles, L., Divakaruni, A. S., & Williams, D. S. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102286 · Cited by 40
“ARPE-19 cells, obtained from American Type Culture Collection (passage 19), and hfRPE from three different donors were maintained as described previously (22).”
BackgroundMethodInfluentialReassessing 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
Pariente, A., Peláez, R., Pérez-Sala, Á., & Larráyoz, I. M. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2019.107746 · Cited by 32
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
“Recently, a rapid differentiation protocol using culture medium supplemented with nicotinamide has been reported to allow the cells to form a polarized epithelium with cobblestone appearance but lacking pigmentation within two to four weeks and to regain RPE functions [51].”
BackgroundRetinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond
Markitantova, Y. V., & Simirskii, V. N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031193 · Cited by 34
Retinal Toxicity Induced by Chemical Agents
de Araújo, D. S. M., Brito, R., Pereira‐Figueiredo, D., dos Santos‐Rodrigues, A., Logu, F. D., Nassini, R., Zin, A., & Calaza, K. D. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158182 · Cited by 30
“For instance, there is an established method for culturing ARPE-19 cells that uses nicotinamide to stimulate cell growth and differentiation [139].”
MethodRethinking of TEER measurement reporting for epithelial cells grown on permeable inserts
Karakoçak, B. B., Keshavan, S., Gunasingam, G., Angeloni, S., Auderset, A., Petri‐Fink, A., & Rothen‐Rutishauser, B. (2023) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2023.106511 · Cited by 28
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Protection of human retinal pigment epithelial cells from oxidative damage using cysteine prodrugs
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“…Aldrich, St Louis, MO), 1% Glutamax (Thermo Fisher Scientific-Gibco, Grand Island, NY), 100 U/ml penicillin/streptomycin (Thermo Fisher Scientific-Gibco, Grand Island, NY) and 10 mM nicotinamide (Merck-Sigma Aldrich, St Louis, MO) to promote differentiation as previously described [85].”
MethodThe CD36 Ligand‐Promoted Autophagy Protects Retinal Pigment Epithelial Cells from Oxidative Stress
Dorion, M., Mulumba, M., Kasai, S., Itoh, K., Lubell, W. D., & Ong, H. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6691402 · Cited by 18
“ARPE-19 cells (American Type Cell Collection) were cultured in complete medium and differentiated as previously described with slight modifications [29].”
Noh, S., Lee, S. J., Cho, C. S., Jo, D. H., Park, K., & Kim, J. H. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.12.012 · Cited by 16
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“22,23 Since inflammation is a critical feature in DME, pro-inflammatory cytokine TNF α was introduced to simulate stress in the cellular environment.”
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Dopamine receptor signaling regulates fibrotic activation of retinal pigmented epithelial cells
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In Vitro Models of Diabetes: Focus on Diabetic Retinopathy
Galgani, G., Bray, G., Martelli, A., Calderone, V., & Citi, V. (2024) · Cells · doi:10.3390/cells13221864 · Cited by 14
Goenka, S., & Simon, S. R. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182111655 · Cited by 13
“Although ARPE-19 can be differentiated and fully polarized with melanization after 4 months of culture [74,75] using a specialized medium with 1% serum or in a shorter span of 1 week by supplementation of exogenous chemical, nicotinamide, to induce differentiation [76], the use of undifferentiated ARPE-19 cells is a r…”
ResultLiu, Y., Guo, Z., Wang, S., Liu, Y., & Wei, Y. (2021) · Marine Drugs · doi:10.3390/md20010015 · Cited by 12
“Construction of Differentiated RPE Cell Monolayer The differentiated RPE cell monolayer was cultured as described in previous studies [39,40].”
MethodMagnetically Controllable and Degradable Milliscale Swimmers as Intraocular Drug Implants
Yıldız, E., Bozuyuk, U., Yildiz, E., Wang, F., Han, M., Karacakol, A. C., Sheehan, D., Yu, Y., & Sitti, M. (2025) · Advanced Science · doi:10.1002/advs.202507569 · Cited by 12
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 14
Ruíz‐Cruz, S., González-Vega, R. I., Robles‐Zepeda, R. E., Reyes‐Díaz, A., López‐Elías, J. A., Álvarez-Ainza, M. L., Cinco-Moroyoqui, F. J., Moreno-Corral, R. A., Wong‐Corral, F. J., Borboa‐Flores, J., et al. (2022) · Metabolites · doi:10.3390/metabo12121203 · Cited by 11
“with the typical structural morphology of healthy cells [76].”
BackgroundRetinal Pigment Epithelium Cell Culture
Klettner, A. (2020) · Springer eBooks · doi:10.1007/978-3-030-28384-1_17 · Cited by 11
Wang, J.-H., Urrutia-Cabrera, D., Lees, J. G., Mora, S. M., Nguyen, T., Hung, S. S. C., Hewitt, A. W., Lim, S. Y., Edwards, T. L., & Wong, R. C. B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043417 · Cited by 10
“Using an established method to induce polarisation of ARPE19 with nicotinamide treatment [21], we verified that ARPE19-KRAB retained the ability to form a monolayer with organised hexagonal RPE morphology, as shown by expression of the tight junction protein ZO-1 (Figure 1C).”
BackgroundMethodGeiller, B., Greigert, V., Hillenbrand, C. A., Gommenginger, C., Beal, L., Brunet, J., Filisetti, D., Villard, O., Denis, J., & Pfaff, A. W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1148037 · Cited by 10
“The use of an established differentiation protocol (20) allowed us to approach primary RPE cell characteristics, like the expression of recognized markers and the ZO-1 localization to tight junctions.”
BackgroundIn vitro laboratory models of proliferative vitreoretinopathy
Gao, A. Y., Haak, A. J., & Bakri, S. J. (2023) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2023.05.007 · Cited by 10
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
Zadeh, M. A., Alany, R. G., Satarian, L., Shavandi, A., Almousa, M. A., Brocchini, S., & Khoder, M. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15051330 · Cited by 9
“This cell line is commonly used for eye research applications due to its convenience and consistency for cell culture studies [64].”
BackgroundRole of FGF and Hyaluronan in Choroidal Neovascularization in Sorsby Fundus Dystrophy
Wolk, A., Hatipoğlu, D., Cutler, A., Ali, M., Bell, L., Qi, J. H., Singh, R., Batoki, J. C., Karle, L., Bonilha, V. L., et al. (2020) · Cells · doi:10.3390/cells9030608 · Cited by 8
“720,000 cells and 100,000 cells were plated per well in each well of a 12-well plate or 24-well plate, respectively using a previously published protocol [36].”
MethodNew Technologies to Study Functional Genomics of Age-Related Macular Degeneration
Nguyen, T., Urrutia-Cabrera, D., Liou, R. H.-C., Luu, C. D., Guymer, R. H., & Wong, R. C. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.604220 · Cited by 9
Zhu, X., Zhang, T., Liu, S., Bai, X., Huang, X., Jiang, M., & Sun, X. (2021) · International Journal of Ophthalmology · doi:10.18240/ijo.2021.08.04 · Cited by 9
NAD+ metabolism and eye diseases: current status and future directions
Liu, S., & Zhang, W. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08692-y · Cited by 7
“Researchers found that NAM induced rapid differen - tiation of ARPE-19 cells, which was reversed by removing supplemented NAM [ 69].”
BackgroundZhou, M., Zhao, Y., Weber, S. R., Gates, C., Carruthers, N. J., Chen, H., Liu, X., Wang, H., Ford, M., Swulius, M. T., et al. (2023) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12373 · Cited by 8
“Though ARPE-19 cells were cultured to confluence so that a monolayer and tight junction had formed, the RPE characteristics of these cells could be improved if they had been left to differentiate for 2 weeks with nicotinamide (Hazim et al., 2019).”
BackgroundBiswal, M. R., Paulson, R. J., Vichare, R., & Lewin, A. S. (2023) · Antioxidants · doi:10.3390/antiox12122129 · Cited by 8
“Following di ff erentiation [26], ARPE-19 cells were subjected to oxidative stress induced using paraquat (1000 µM) treatment. employed ZO-1 immunocytochemistry on cells cultured in 8-well chamber slides.”
BackgroundMethodInfluentialKim, J., Song, Y., Jolly, A. L., Hwang, T., Kim, S., Lee, B., Jang, J., Jo, D. H., Baek, K., Liu, T., et al. (2024) · Advanced Materials Technologies · doi:10.1002/admt.202400634 · Cited by 8
Alonso-Alonso, M. L., Srivastava, G. K., Usategui‐Martín, R., García-Gutiérrez, M. T., Jimeno, J. C. P., & Fernandez‐Bueno, I. (2020) · Stem Cells International · doi:10.1155/2020/9463548 · Cited by 8
“Besides, NIC has been used to induce the differentiation of ARPE-19 cells [38].”
MethodShang, P., Stepicheva, N. A., Liu, H., Chowdhury, O., Franks, J. M., Sun, M., Hose, S., Ghosh, S., Yazdankhah, M., Strizhakova, A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111979 · Cited by 8
“However, the limitations of this technique are low transepithelial resistance, lack of pigmentation, and abnormal karyotype [4].”
BackgroundEffects of FTMT Expression by Retinal Pigment Epithelial Cells on Features of Angiogenesis
Buyandelger, U., Walker, D. G., Yanagisawa, D., Morimura, T., & Tooyama, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103635 · Cited by 8
“ARPE-19 cells were differentiated according to a previously published method with modifications [37].”
BackgroundMethodMetabolic Phenotyping of Healthy and Diseased Human RPE Cells
Rizwan, S., Toothman, B., Li, B., Engel, A. L., Lim, R. R., Niernberger, S., Lu, J., Ratliff, C., Xiang, Y., Eminhizer, M., et al. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.11.5 · Cited by 7
Singh, M. K., Singh, L., Atilano, S. R., Chwa, M., Salimiaghdam, N., & Kenney, M. C. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04832-6 · Cited by 9
“We utilized the method used by Hazim et al. to efficiently differentiate ARPE-19 cells in vitro [26, 27].”
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“MEM-Nic media contained MEM alpha with GlutaMAX, 1% FBS, 1% Penicillin/Streptomycin, 1% N1 supplement (a specific cell culture supplement to promote the differentiation of neural cells), taurine (0.25 mg/ml), hydrocortisone (20 ng/ml), triiodo-thyronine (0.013 ng/ml), and 10 mM nicotinamide [31].”
InfluentialTissue engineering of outer blood retina barrier for therapeutic development
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Effects of galectin-3 protein on UVA-induced damage in retinal pigment epithelial cells
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“Although it has been shown that ARPE-19 do express various proteins and phenotype that are relevant for the RPE phenotype [29, 30], literature search indicates that more predictive preclinical in vitro models are required when working with cell line, such as ARPE-19 [31].”
BackgroundGatta, M., Dovizio, M., Milillo, C., Ruggieri, A. G., Sallese, M., Antonucci, I., Trofimov, A. V., Khavinson, V., Trofimova, S., Bruno, A., et al. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-10911-x · Cited by 5
“These results are consistent are a common model for studying retinal function [68, 69], their standard culture medium already contains elevated glucose levels higher than physiological norms.”
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
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“ARPE-19 cells were cultured using a method previously shown to increase epithelial cell morphology, cytoskeletal organization and RPE-related functions [42].”
MethodModeling Choroideremia Disease with Isogenic Induced Pluripotent Stem Cells
Fonseca, A. F., Coelho, R., Lopes‐da‐Silva, M., de Lemos, L., Hall, M. J., Oliveira, D., Falcão, A. S., Tenreiro, S., Seabra, M. C., & Antas, P. (2024) · Stem Cells and Development · doi:10.1089/scd.2024.0105 · Cited by 5
“12,13 In addition, ARPE-19 cells produce some RPE-speci fi c mRNA transcripts without the corresponding protein expression, such as RPE65, BEST1, and CLDN19, leading to an incompletely differentiated phenotype.”
Grigoryan, E. N., & Markitantova, Y. V. (2025) · Biomedicines · doi:10.3390/biomedicines13071552 · Cited by 4
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
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Kuznetsova, A. V. (2022) · Russian Journal of Developmental Biology · doi:10.1134/s1062360422060054 · Cited by 4
“Recently, the role of nicotinamide in the return of RPE cells from a dedifferentiated with EMT state to a differentiated state was closely studied in vitro (Hazim et al., 2019; Boles et al., 2020; Zhou et al., 2020).”
BackgroundMachine learning-based 3D segmentation of mitochondria in polarized epithelial cells
Hultgren, N. W., Zhou, T., & Williams, D. S. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101882 · Cited by 4
Kwon, Y., & Han, Z. (2024) · Advanced Therapeutics · doi:10.1002/adtp.202400030 · Cited by 5
Isolation of Primary Porcine Retinal Pigment Epithelial Cells for In Vitro Modeling
Paterson, C. A., Weatherston, D., Teeples, T., & Vargis, E. (2024) · Journal of Visualized Experiments · doi:10.3791/66079 · Cited by 3
Geiller, B., Cevallos, C., Tsybenko, I., Arnoux, L., Felder‐Schmittbuhl, M., & Pfaff, A. W. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1607247 · Cited by 3
“Human RPE ARPE-19 cells were differentiated according to the protocol described by Hazim et al. (12).”
Fabian-Jessing, B. K., Askou, A. L., Jakobsen, T. S., Adsersen, R. L., Lindholm, A. B., Bjerre, A. K. K., Alsing, S., Bek, T., Aagaard, L., & Corydon, T. J. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.102833 · Cited by 3
Accelerated maturation of ARPE ‐19 cells for the translational assessment of gene therapy
Bernd, J., Plastino, F., Karayannis, J. J., Kvanta, A., Locri, F., & André, H. (2024) · The FASEB Journal · doi:10.1096/fj.202301707rr · Cited by 3
“12,13 In addition, several laminins occur naturally in the multilayered Bruch's membrane with laminin 521, 511, 332, and 111 as the main isoforms expressed.”
Kaplan, O., Koç, E., Türk, S., Küçükkılınç, T. T., Göktaş, Z., & Çelebi̇er, M. (2024) · European Journal of Integrative Medicine · doi:10.1016/j.eujim.2024.102414 · Cited by 3
Zubieta, D., Warden, C., Bhattacharya, S., & Brantley, M. A. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47040224 · Cited by 3
“TUDCA’s ability to induce autophagy flux was observed in both ARPE-19 cells, a human RPE cell line commonly used for research [42], and iPSC-derived RPE cells, which are derived from pluripotent stem cells and more closely mimic the native RPE’s characteristics [43].”
Complement C3 Activation in the Human Retinal Pigment Epithelium
Schikora, J., Nickel, A., Bergert, J., Hähnel, R., Dort, A., King, B. C., Schayan-Araghi, S. Y., Banerjee, P., Wolf, H., May‐Simera, H., et al. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.9.67 · Cited by 3
“55 Application of HM protocols, as described by Hazim et al., 37 partially improved epithelial traits.”
Khan, A. Z., Utheim, T. P., Moe, M. C., Aass, H. C. D., Sapkota, D., Vallenari, E. M., & Eidet, J. R. (2020) · Current Eye Research · doi:10.1080/02713683.2020.1809001 · Cited by 3
The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells
Chang, Q., Chen, S., & Yang, T. (2022) · The Open Biochemistry Journal · doi:10.2174/1874091x-v16-e2206270 · Cited by 3
Hamuro, J., Yamashita, T., Otsuki, Y., Hiramoto, N., Adachi, M., Miyatani, T., Tanaka, H., Ueno, M., Kinoshita, S., & Sotozono, C. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.5.9 · Cited by 3
“Hazim et al. 27 recently reported that during NAM-induced differentiation, the mitochondria became larger with more tightly folded The PTEN versus SIRT3 balance in mitochondria may be critical as one of the causal elements in the degeneration of RPE cells.”
InfluentialMiyatani, T., Tanaka, H., Numa, K., Uehara, A., Otsuki, Y., Hamuro, J., Kinoshita, S., & Sotozono, C. (2024) · Scientific Reports · doi:10.1038/s41598-024-73145-w · Cited by 3
“Cell morphology was monitored periodically by culturing ARPE-19 cells in standard medium (DMEM/F12) or differentiation medium (MEM-Nic) for 4 weeks as previously reported 17,21 .”
InfluentialHultgren, N. W., Petcherski, A., Torriano, S., Komirisetty, R., Sharma, M. B., Zhou, T., Burgess, B. L., Ngo, J., Osto, C. A., Shabane, B., et al. (2024) · PNAS Nexus · doi:10.1093/pnasnexus/pgae500 · Cited by 2
Regulation of RPE65 expression in human retinal pigment epithelium cells
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“We adopted the RPE differentiation protocol of Hazim et al. 9 .”
Safety and effectiveness of vital dyes for intraocular surgery
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Using Small Molecules to Reprogram RPE Cells in Regenerative Medicine for Degenerative Eye Disease
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Age-Related Macular Degeneration and its Current Treatment Strategies: An Updated Review
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“…to the use of ARPE-19 cells due to their lack of typical RPE phenotype and functionality may be alleviated using a differentiation protocol recently described, involving nicotinamide supplementation in the culture medium to obtain mature RPE showing a cobblestone morphology within a few weeks 13 .”
Yang, X., Xu, W., Xie, H., Guo, X., Zhu, F., Xing, Y., & Chen, C. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1718715 · Cited by 1
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A critical role for mitochondrial dynamics in cigarette smoke condensate-induced RPE senescence
Zhou, Q., Zhang, Z., Wu, Y. J., Dong, C., Wu, C.-C., Handa, J. T., Ma, J., & Wang, S. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.06.060 · Cited by 1
Investigating the effects of 7‐ketocholesterol on retinal pigment epithelium bioenergetics
Dey, S., Catchpole, T., Takacs, A., & Csaky, K. G. (2023) · The FASEB Journal · doi:10.1096/fj.202300101r · Cited by 1
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MicroRNA Regulation for Inflammasomes in High Glucose‐Treated ARPE‐19 Cells
Kim, J. H., Yu, H. S., Kang, J. H., Hong, E. H., Kang, M. H., Seong, M., Cho, H., & Shin, Y. U. (2024) · Journal of Ophthalmology · doi:10.1155/2024/3654690 · Cited by 1
“ARPE-19 cells were obtained from the American Type Culture Collection and cultured in Dulbecco’s modifed Eagle’s medium/F-12 (DMEM/F12, Gibco, Grand Island, NY, USA) supplemented with 10% fetal bovine serum (FBS, Gibco) and 1% penicillin/streptomycin (Gibco) [13, 14].”
MethodPark, H., Papanastasi, E., Blanchard, G., Chiticariu, E., Bachmann, D., Plomann, M., Morice‐Picard, F., Vabres, P., Smahi, A., Huber, M., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.16.877498
Metadata
- Authors
- Hazim, R. A., Volland, S., Yen, A., Burgess, B. L., & Williams, D. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Williams, David S.
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 179
- Pages
- 18-24
- ISSN
- 0014-4835 (ISSN-L)
- PMC
- PMC6360117
- OpenAlex
- W2897486375
- Cited by
- 126
- References
- 41
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 26 · 2023: 16 · 2022: 15 · 2021: 7 · 2020: 18 · 2019: 4
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (P30EY0331, R01EY013408, R01EY027442, F31EY026805)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- retinal pigment epithelium, RPE differentiation, nicotinamide, epithelial morphology, cytoskeletal organization, vitamin B metabolism
- MeSH terms
- Bestrophins, Retinoid Isomerohydrolase, Cell Differentiation, Cell Line, Cytoskeleton, Gene Expression Regulation, Humans, Microvilli, Niacinamide, Vitamin B Complex, Biomarkers, Fluorescent Antibody Technique, Indirect, cis-trans-Isomerases, Integrin beta Chains, Retinal Pigment Epithelium, Real-Time Polymerase Chain Reaction, Occludin, Zonula Occludens-1 Protein
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