ArticleInvestigative ophthalmology & visual science2012
Expression of toll-like receptor 4 contributes to corneal inflammation in experimental dry eye disease.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Cluster Analysis of Dry Eye Disease Models Based on Immune Cell Parameters - New Insight Into Therapeutic Perspective.Frontiers in immunology · 2020Pooled it
- Palladium nanozyme loaded metal-organic framework eyedrops alleviate oxidative stress for dry eye treatment.Journal of nanobiotechnology · 2026Article
- Mechanisms of Mesenchymal Stem Cell-Derived Exosomes in Dry Eye Disease: From Inflammation Pathways to Therapeutic Prospects.Stem cells international · 2026Review
- Mechanisms of acupuncture in the treatment of dry eye disease: narrative review of experimental studies.International ophthalmology · 2025Review
- Assessing the Independent and Combined Effects of Hyperosmolarity and Inflammatory Stress on Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2025Article
- Keratoconjunctivitis Sicca in Sjögren Disease: Diagnostic Challenges and Therapeutic Advances.International journal of molecular sciences · 2025Review
- TLR4 deficiency does not alter glaucomatous progression in a mouse model of chronic glaucoma.Scientific reports · 2025Article
- Review
- Toll-like receptor 2 deficiency exacerbates corneal angiogenesis in injury by impairing regulatory T cells.Theranostics · 2025Article
- BMSC-derived exosomes regulate the Treg/Th17 balance through the miR-21-5p/TLR4/MyD88/NF-κB pathway to alleviate dry eye symptoms in mice.In vitro cellular & developmental biology. Animal · 2024Article
- Local administration of myeloid-derived suppressor cells prevents progression of immune-mediated dry eye disease.Experimental eye research · 2024Article
- Protective effects of insulin on dry eye syndrome via TLR4/NF-κB pathway: based on network pharmacology andFrontiers in pharmacology · 2024Article
- Inflammation of Dry Eye Syndrome: A Cellular Study of the Epithelial and Macrophagic Involvement of NFAT5 and RAGE.International journal of molecular sciences · 2023Article
- Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion.International journal of molecular sciences · 2023Article
- Bacteria and Dry Eye: A Narrative Review.Journal of clinical medicine · 2022Review
- IGFBP-3 Regulates Mitochondrial Hyperfusion and Metabolic Activity in Ocular Surface Epithelia during Hyperosmolar Stress.International journal of molecular sciences · 2022Article
- Acupuncture Alleviates Corneal Inflammation in New Zealand White Rabbits with Dry Eye Diseases by RegulatingEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Experimental Models, Induction Protocols, and Measured Parameters in Dry Eye Disease: Focusing on Practical Implications for Experimental Research.International journal of molecular sciences · 2021Review
- Autoimmunity in dry eye disease - An updated review of evidence on effector and memory Th17 cells in disease pathogenicity.Autoimmunity reviews · 2021Review
- Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Purpose. To investigate the corneal expression of toll-like receptor (TLR) 4 and determine its contribution to the immunopathogenesis of dry eye disease (DED). Methods. Seven to 8-week-old female C57BL/6 mice were housed in a controlled environment chamber and administered scopolamine to induce experimental DED. Mice received intravenous TLR4 inhibitor (Eritoran) to block systemic TLR4-mediated activity. The expression of TLR4 by the corneal epithelium and stroma was evaluated using real-time polymerase chain reaction and flow cytometry. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease severity. The corneal expression of proinflammatory cytokines (IL-1β, IL-6, TNF, and CCL2), corneal infiltration of CD11b(+) antigen-presenting cells, and lymph node frequency of mature MHC-II(hi) CD11b(+) cells were assessed. Results. The epithelial cells of normal corneas expressed TLR4 intracellularly; however, DED significantly increased the cell surface expression of TLR4. Similarly, flow cytometric analysis of stromal cells revealed a significant increase in the expression of TLR4 proteins by DED-induced corneas as compared with normal corneas. DED increased the mRNA expression of TLR4 in corneal stromal cells, but not epithelial cells. TLR4 inhibition decreased the severity of CFS and significantly reduced the mRNA expression of IL-1β, IL-6, and TNF. Furthermore, TLR4 inhibition significantly reduced the corneal infiltration of CD11b(+) cells and the lymph node frequency of MHC-II(hi) CD11b(+) cells. Conclusions. These results suggest that DED increases the corneal expression of TLR4 and that TLR4 participates in the inflammatory response to ocular surface desiccating stress.
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Registered trials
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.