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Cited by 269Retinal Development and DisordersRetinal Diseases and TreatmentsRetinal Imaging and Analysis

Transcriptome analysis and molecular signature of human retinal pigment epithelium

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Strunnikova, N.V., Maminishkis, A., Barb, J.J., Wang, F., Zhi, C., Sergeev, Y., Chen, W., Edwards, A.O. +5 more·2010·Human Molecular Genetics
DOI 10.1093/hmg/ddq129PMC PMC2876890
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Abstract

Retinal pigment epithelium (RPE) is a polarized cell layer critical for photoreceptor function and survival. The unique physiology and relationship to the photoreceptors make the RPE a critical determinant of human vision. Therefore, we performed a global expression profiling of native and cultured human fetal and adult RPE and determined a set of highly expressed 'signature' genes by comparing the observed RPE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues. Using stringent selection criteria of at least 10-fold higher expression in three distinct preparations, we identified 154 RPE signature genes, which were validated by qRT-PCR analysis in RPE and in an independent set of 11 tissues. Several of the highly expressed signature genes encode proteins involved in visual cycle, melanogenesis and cell adhesion and Gene ontology analysis enabled the assignment of RPE signature genes to epithelial channels and transporters (ClCN4, BEST1, SLCA20) or matrix remodeling (TIMP3, COL8A2). Fifteen RPE signature genes were associated with known ophthalmic diseases, and 25 others were mapped to regions of disease loci. An evaluation of the RPE signature genes in a recently completed AMD genomewide association (GWA) data set revealed that TIMP3, GRAMD3, PITPNA and CHRNA3 signature genes may have potential roles in AMD pathogenesis and deserve further examination. We propose that RPE signature genes are excellent candidates for retinal diseases and for physiological investigations (e.g. dopachrome tautomerase in melanogenesis). The RPE signature gene set should allow the validation of RPE-like cells derived from human embryonic or induced pluripotent stem cells for cell-based therapies of degenerative retinal diseases.

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  • Primary RPE, iPS-RPE, and ES-RPE cells can form well-differentiated, RPE-like cultures, demonstrating a polarized epithelial organization, close approximation of native RPE gene and protein expression, and the ability to perform RPE functions such as ingestion and degradation of OSs over a time-course comparable to in vivo.

    “An important characteristic of primary RPE, iPS-RPE, and ES-RPE cells is that they can form well-differentiated, RPE-like cultures, demonstrating a polarized epithelial organization (Fig. 2), close approximation of native RPE gene and protein expression, and the ability to perform RPE functions, such as the ingestion and degradation of OSs over a time-course that is comparable to that in vivo (Mam”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Strunnikova et al., 2010

  • Expression of "RPE signature" genes is important; however, more importantly, the resulting proteins must be localized properly; e.g. the Na+/K+-ATPase should be in the apical membrane.

    “Expression of “RPE signature” genes is important (Strunnikova et al., 2010); however, more importantly, the resulting proteins must be localized properly; e.g. the Na+/K+-ATPase should be in the apical membrane (not basal as is the case in RPE-J cells).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Strunnikova et al., 2010

  • Over the years, with numerous passages, the ability of ARPE-19 cells to demonstrate characteristics of differentiated RPE has diminished.

    “Over the years, with numerous passages, the ability of cells of this line to demonstrate characteristics of differentiated RPE has diminished (Strunnikova et al., 2010; Lehmann et al., 2014).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Strunnikova et al., 2010

  • There are now reproducible protocols that generate RPE monolayers with a well-differentiated phenotype for primary RPE cultures, RPE cells derived from stem cells, and ARPE-19 cells.

    “As discussed above, there are now reproducible protocols that generate RPE monolayers with a well-differentiated phenotype, not only for primary RPE cultures (Gibbs and Williams, 2003; Maminishkis et al., 2006; Strunnikova et al., 2010; Blenkinsop et al., 2013; Toops et al., 2014) and RPE cells derived from stem cells (Idelson et al., 2009; Buchholz et al., 2013; Gong et al., 2015; Maruotti et al.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Strunnikova et al., 2010

  • RPE cell lines lack some RPE polarity features, have reduced expression of a large proportion of RPE signature genes, and typically exhibit much slower phagosome degradation kinetics than primary RPE cultures.

    “cultures of RPE cell lines, which have been reported to lack some RPE polarity features (Lehmann et al., 2014), have reduced expression of a large proportion of “RPE signature genes” (Strunnikova et al., 2010), and typically exhibit kinetics of phagosome degradation that is much slower than that found in vivo and in primary RPE cultures (Finnemann et al., 2002; Mazzoni et al., 2014).”

    From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Strunnikova et al., 2010

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Research works printed but not linked: 2

  1. [66]Swaroop A. Chew E.Y. Bowes Rickman C. Abecasis G.R. Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration Annu. Rev. Genomics Hum. Genet. 2009 10 19 43 doi:10.1146/annurev.genom.9.081307.164350 19405847 PMC3469316 · DOI · Paper page
  2. [85]Jolliffe I.T. Springer Series in Statistics: Principal Components Analysis 2002 New York Springer 103 134

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Authors
Strunnikova, N. V., Maminishkis, A., Barb, J. J., Wang, F., Zhi, C., Sergeev, Y., Chen, W., Edwards, A. O., Stambolian, D., Abecasis, G., Swaroop, A., Munson, P. J., & Miller, S. S.
Affiliations
  • National Institutes of Health (US)
  • University of Michigan (US)
  • University of Oregon (US)
  • University of Pennsylvania (US)
Corresponding author
Miller, S.S.
ORCID
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2010-04-01
Volume
19
Issue
12
Pages
2468-2486
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
DOI
10.1093/hmg/ddq129
PMC
PMC2876890
OpenAlex
W2103693357
Cited by
269
References
91
Citations by year
2026: 6 · 2025: 14 · 2024: 14 · 2023: 15 · 2022: 21 · 2021: 17 · 2020: 26 · 2019: 19 · 2018: 12 · 2017: 23 · 2016: 17 · 2015: 22 · 2014: 19 · 2013: 10 · 2012: 14
FWCI
5.74
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Human Molecular Genetics (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Eye Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords
retinal pigment epithelium, gene expression profiling, transcriptome, AMD, age-related macular degeneration, TIMP-3, visual cycle, melanogenesis, dopachrome tautomerase, CHRNA3, retinal disease, cell therapy
MeSH terms
Adult, Amino Acid Sequence, Cells, Cultured, Humans, Macular Degeneration, Molecular Sequence Data, Gene Expression, Intramolecular Oxidoreductases, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Genome-Wide Association Study, Retinal Pigment Epithelium

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