Claudin-19 and the barrier properties of the human retinal pigment epithelium
Open accessAbstract
PURPOSE: The retinal pigment epithelium (RPE) separates photoreceptors from choroidal capillaries, but in age-related macular degeneration (AMD) capillaries breach the RPE barrier. Little is known about human RPE tight junctions or the effects of serum on the retinal side of the RPE. METHODS: Cultured human fetal RPE (hfRPE) was assessed by the transepithelial electrical resistance (TER) and the transepithelial diffusion of methylated polyethylene glycol (mPEG). Claudins and occludin were monitored by quantitative RT-PCR, immunoblotting, and immunofluorescence. RESULTS: Similar to freshly isolated hfRPE, claudin-19 mRNA was 25 times more abundant than claudin-3. Other detectable claudin mRNAs were found in even lesser amounts, as little as 3000 times less abundant than claudin-19. Claudin-1 and claudin-10b were detected only in subpopulations of cells, whereas others were undetectable. Knockdown of claudin-19 by small interfering RNA (siRNA) eliminated the TER. siRNAs for other claudins had minimal effects. Serum affected tight junctions only when presented to the retinal side of the RPE. The TER increased 2 times, and the conductance of K(+) relative to Na(+) decreased without affecting the permeability of mPEG. These effects correlated with increased steady-state levels of occludin. CONCLUSIONS: Fetal human RPE is a claudin-19-dominant epithelium that has regional variations in claudin-expression. Apical serum decreases RPE permeability, which might be a defense mechanism that would retard the spread of edema due to AMD.
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TER is a critical measure of the barrier function of the RPE, which is established by the expression and circumferential localization of tight junction proteins such as ZO-1, occludin, and specific claudins.
“The TER is a critical measure of the barrier function of the RPE, which is established by the expression and circumferential localization of tight junction proteins, such as zonula occludens (ZO)-1, occludin, and specific claudins (Rahner et al., 2004; Peng et al., 2011).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Peng et al., 2011
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The cell biology of the retinal pigment epithelium
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- Authors
- Peng, S., Rao, V. S., Adelman, R. A., & Rizzolo, L. J.
- Affiliations
- Harbin University (CN)
- Yale University (US)
- Corresponding author
- Peng, Shaomin
- Rao, Veena S.
- Adelman, Ron A.
- Rizzolo, Lawrence J.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2011-03-14
- Volume
- 52
- Issue
- 3
- Pages
- 1392
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3101667
- OpenAlex
- W1984271994
- Cited by
- 99
- References
- 53
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 5 · 2023: 11 · 2021: 7 · 2020: 11 · 2019: 6 · 2018: 5 · 2017: 8 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 9
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (P30EY000785, EY000785)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- claudin-19, retinal pigment epithelium, tight junctions, blood-retinal barrier, age-related macular degeneration, transepithelial electrical resistance, occludin, claudin expression, claudin-3, claudin-1, edema
- MeSH terms
- Cells, Cultured, Gestational Age, Humans, Membrane Proteins, Permeability, Polyethylene Glycols, RNA, Messenger, Immunoblotting, Electric Impedance, Fluorescent Antibody Technique, Indirect, Tight Junctions, Reverse Transcriptase Polymerase Chain Reaction, Gene Silencing, RNA, Small Interfering, Retinal Pigment Epithelium, Claudins, Occludin
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