The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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).”
Background
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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