ArticleInvestigative ophthalmology & visual science2010
Barrier dysfunction of the corneal endothelium in response to TNF-alpha: role of p38 MAP kinase.
Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- Activating transcription factor 6 is involved in the beneficial effects of growth hormone-releasing hormone antagonists in the corneal endothelium.Frontiers in ophthalmology · 2026Article
- Exploring biomarkers for keratoconus: current insights and future directions.Molecular biology reports · 2025Review
- Effects of Benzalkonium Chloride, a Preservative in Topical Drugs, on the Barrier Function of Human Corneal Epithelial Cells.Translational vision science & technology · 2025Article
- M2a Macrophage-Dominant Microenvironment in Inflammation Attenuation and Wound Healing of Human Corneal Endothelial Cells.Investigative ophthalmology & visual science · 2025Article
- Transcription factor 4 promotes increased corneal endothelial cellular migration by altering microtubules in Fuchs endothelial corneal dystrophy.Scientific reports · 2024Article
- Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system.Lab on a chip · 2024Article
- Fusogenic liposome-coated nanoparticles for rapid internalization into donor corneal endothelial tissue to enable prophylaxis before transplantation.Nanoscale advances · 2023Article
- Manufacturing of human corneal endothelial grafts.The ocular surface · 2023Article
- Investigating the Role of TGF-β Signaling Pathways in Human Corneal Endothelial Cell Primary Culture.Cells · 2023Article
- Corneal Edema in InducibleCells · 2023Article
- SIRT1 Activation Using CRISPR/dCas9 Promotes Regeneration of Human Corneal Endothelial Cells through Inhibiting Senescence.Antioxidants (Basel, Switzerland) · 2020Article
- Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in CMV-Positive Posner-Schlossman Syndrome Patients.Investigative ophthalmology & visual science · 2020Article
- In Vitro Culture of Human Corneal Endothelium on Non-Mulberry Silk Fibroin Films for Tissue Regeneration.Translational vision science & technology · 2020Article
- TNF-alpha inhibits pregnancy-adapted CaMolecular and cellular endocrinology · 2019Article
- Engineering of Human Corneal Endothelial CellsInternational journal of medical sciences · 2019Review
- Critical role of endoplasmic reticulum stress in chronic endothelial activation-induced visual deficits in tie2-tumor necrosis factor mice.Journal of cellular biochemistry · 2018Article
- Inflammatory cytokine TNF-α promotes corneal endothelium apoptosis via upregulating TIPE2 transcription during corneal graft rejection.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2018Article
- Differential Mechanisms of Septic Human Pulmonary Microvascular Endothelial Cell Barrier Dysfunction Depending on the Presence of Neutrophils.Frontiers in immunology · 2018Article
- Article
- Inhibition of Murine Pulmonary Microvascular Endothelial Cell Apoptosis Promotes Recovery of Barrier Function under Septic Conditions.Mediators of inflammation · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeTNF-alpha is elevated in the cornea and aqueous humor during allograft rejection and anterior uveitis. The authors investigated the involvement of p38 MAP kinase in the TNF-alpha-induced loss of barrier integrity in monolayers of cultured bovine corneal endothelial cells.
methodsTransendothelial electrical resistance (TER), a measure of barrier integrity, was determined by electrical cell-substrate impedance sensing. Barrier integrity was further assessed in terms of permeability to FITC dextran. Reorganization of the apical junctional complex (AJC) in response to TNF-alpha was visualized by immunofluorescence. The expression of TNF-alpha receptors was confirmed by RT-PCR. Activation of p38 MAP kinase in response to TNF-alpha was determined by Western blot analysis.
resultsExposure to TNF-alpha induced a continuous decline in TER that persisted for more than 20 hours. It also led to a significant increase in permeability to FITC dextran. At the AJC, the cytokine caused disassembly of microtubules, disruption of perijunctional actomyosin ring (PAMR), and dislocation of ZO-1 and cadherins. Western blot analysis showed that TNF-alpha also led to the activation of p38 MAP kinase. All these responses to the cytokine were opposed by treatment with SB-203580, a selective p38 MAP kinase inhibitor. TNFR1, but not TNFR2, was expressed in untreated cells with no change in the expression pattern on treatment with the cytokine.
conclusionsTNF-alpha breaks down the barrier integrity of corneal endothelium, concomitant with the disruption of PAMR, remodeling of AJC, and disassembly of microtubules. These effects are mediated by transient activation of p38 MAP kinase. Thus, the TNF-alpha-induced barrier dysfunction in the corneal endothelium can be suppressed by inhibitors of p38 MAP kinase and agents downstream of the kinase that affect the cytoskeleton.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.