Research resource: nuclear receptor atlas of human retinal pigment epithelial cells: potential relevance to age-related macular degeneration
Open accessAbstract
Retinal pigment epithelial (RPE) cells play a vital role in retinal physiology by forming the outer blood-retina barrier and supporting photoreceptor function. Retinopathies including age-related macular degeneration (AMD) involve physiological and pathological changes in the epithelium, severely impairing the retina and effecting vision. Nuclear receptors (NRs), including peroxisome proliferator-activated receptor and liver X receptor, have been identified as key regulators of physiological pathways such as lipid metabolic dysregulation and inflammation, pathways that may also be involved in development of AMD. However, the expression levels of NRs in RPE cells have yet to be systematically surveyed. Furthermore, cell culture lines are widely used to study the biology of RPE cells, without knowledge of the differences or similarities in NR expression and activity between these in vitro models and in vivo RPE. Using quantitative real-time PCR, we assessed the expression patterns of all 48 members of the NR family plus aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator in human RPE cells. We profiled freshly isolated cells from donor eyes (in vivo), a spontaneously arising human cell line (in vitro), and primary cell culture lines (in vitro) to determine the extent to which NR expression in the cultured cell lines reflects that of in vivo. To evaluate the validity of using cell culture models for investigating NR receptor biology, we determined transcriptional activity and target gene expression of several moderately and highly expressed NRs in vitro. Finally, we identified a subset of NRs that may play an important role in pathobiology of AMD.
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In freshly isolated human RPE, expression of PPARα and PPARβ/δ was relatively high, while PPARγ was not detected.
“Expression of PPARα and β/δ was relatively high in freshly isolated human RPE; however, PPARγ was not detected.”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Dwyer et al., 2011
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Implications of genetic variation in the complement system in age-related macular degeneration
de Jong, S., Gagliardi, G., Garanto, A., de Breuk, A., Lechanteur, Y. T. E., Katti, S., van den Heuvel, L. P., Volokhina, E. B., & den Hollander, A. I. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100952 · Cited by 71 · see citing works
- Authors
- Dwyer, M. A., Kazmin, D., Hu, P., McDonnell, D. P., & Malek, G.
- Affiliations
- Duke University (US)
- Corresponding author
- Malek, Goldis
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2011-02-01
- Volume
- 25
- Issue
- 2
- Pages
- 360-372
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC3386542
- OpenAlex
- W2024991121
- Cited by
- 61
- References
- 94
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 2 · 2014: 6 · 2013: 3 · 2012: 3
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (R01EY020868, P30EY005722)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048807, DK-48807, R37DK048807)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- nuclear receptors, retinal pigment epithelium, age-related macular degeneration, peroxisome proliferator-activated receptors, liver X receptor, aryl hydrocarbon receptor, ARNT, gene expression profiling, cell culture model, transcriptional activity, lipid metabolism, inflammation, retinopathy
- MeSH terms
- Age Factors, Atlases as Topic, Cell Line, Genotype, Humans, Macular Degeneration, Transcription, Genetic, Immunoblotting, Gene Expression, Polymerase Chain Reaction, Receptors, Cytoplasmic and Nuclear, Receptors, Aryl Hydrocarbon, Aryl Hydrocarbon Receptor Nuclear Translocator, Retinal Pigment Epithelium
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