Plasma membrane protein polarity and trafficking in RPE cells: past, present and future
Open accessAbstract
The retinal pigment epithelium (RPE) comprises a monolayer of polarized pigmented epithelial cells that is strategically interposed between the neural retina and the fenestrated choroid capillaries. The RPE performs a variety of vectorial transport functions (water, ions, metabolites, nutrients and waste products) that regulate the composition of the subretinal space and support the functions of photoreceptors (PRs) and other cells in the neural retina. To this end, RPE cells display a polarized distribution of channels, transporters and receptors in their plasma membrane (PM) that is remarkably different from that found in conventional extra-ocular epithelia, e.g. intestine, kidney, and gall bladder. This characteristic PM protein polarity of RPE cells depends on the interplay of sorting signals in the RPE PM proteins and sorting mechanisms and biosynthetic/recycling trafficking routes in the RPE cell. Although considerable progress has been made in our understanding of the RPE trafficking machinery, most available data have been obtained from immortalized RPE cell lines that only partially maintain the RPE phenotype and by extrapolation of data obtained in the prototype Madin-Darby Canine Kidney (MDCK) cell line. The increasing availability of RPE cell cultures that more closely resemble the RPE in vivo together with the advent of advanced live imaging microscopy techniques provides a platform and an opportunity to rapidly expand our understanding of how polarized protein trafficking contributes to RPE PM polarity.
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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 Lehmann et al., 2014
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 Lehmann et al., 2014
Loss of cilia in adult RPE is an artifact introduced if the neural retina is removed from the RPE.
“consistent with a recent study that suggests loss of cilia in adult RPE is an artifact that is introduced if the neural retina is removed from the RPE (Lehmann 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 Lehmann et al., 2014
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References 162 · Cited by 122
Research works printed but not linked: 1
- Bok D Hollyfield J Autoradiographic studies on the polarity of plasma membrane receptors in retinal pigment epithelial cells The Structure of the Eye 1982 247 256 Elsevier New York, NY
- Authors
- Lehmann, G. L., Benedicto, I., Philp, N. J., & Rodriguez-Boulan, E.
- Affiliations
- Weill Cornell Medicine (US)
- Thomas Jefferson University (US)
- Corresponding author
- Philp, Nancy J.
- Rodriguez-Boulan, Enrique
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 126
- Pages
- 5-15
- ISSN
- 0014-4835 (ISSN-L)
- PMC
- PMC4502961
- OpenAlex
- W1981279491
- Cited by
- 122
- References
- 162
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 14 · 2023: 10 · 2022: 9 · 2021: 13 · 2020: 16 · 2019: 6 · 2018: 11 · 2017: 14 · 2016: 6 · 2015: 7 · 2014: 1
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (GM34107, EY08538, EY022165, EY012042)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- retinal pigment epithelium, plasma membrane polarity, protein trafficking, polarized transport, protein recycling, MDCK cells, subretinal space
- MeSH terms
- Animals, Biological Transport, Cell Membrane, Dogs, Humans, Membrane Proteins, Cell Polarity, Protein Sorting Signals, Retinal Pigment Epithelium
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