ArticlePloS one2016
Synergistic Effect of Artificial Tears Containing Epigallocatechin Gallate and Hyaluronic Acid for the Treatment of Rabbits with Dry Eye Syndrome.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 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
- Interactions of Mucomimetic Polymers and Meibomian Surface Films upon Exposure to Environmental Stressors.Biomolecules · 2026Article
- Efficacy and mechanism of flavonoids in improving dry eye disease: a systematic review of animal studies.International journal of ophthalmology · 2026Review
- The Role of Nutraceuticals in Age-Related Ocular Diseases.Molecules (Basel, Switzerland) · 2025Review
- Ocular tear fluid biomarkers collected by contact lenses.Biochemical and biophysical research communications · 2024Article
- The Mid-Term Effect of Preservative-Free Artificial Tears Containing Hyaluronic Acid on Dry Eye Incidence after Cataract Surgery: A Retrospective Cohort Study.Diagnostics (Basel, Switzerland) · 2024Article
- The Usage of Different Hyaluronic-Acid-Containing Artificial Tears and the Treatment Outcome of Intense Pulsed Light Therapy for Dry Eye Disease: A Retrospective Cohort Study.Diagnostics (Basel, Switzerland) · 2024Article
- Benzalkonium chloride-induced dry eye disease animal models: Current understanding and potential for translational research.Indian journal of ophthalmology · 2023Review
- Experimental Models, Induction Protocols, and Measured Parameters in Dry Eye Disease: Focusing on Practical Implications for Experimental Research.International journal of molecular sciences · 2021Review
- Efficacy of Artificial Tears Based on an Extract ofInternational journal of molecular sciences · 2021Article
- Development of Lutein-Containing Eye Drops for the Treatment of Dry Eye Syndrome.Pharmaceutics · 2021Article
- Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model.Pharmaceutics · 2021Article
- Olive Pomace Phenolic Compounds and Extracts Can Inhibit Inflammatory- and Oxidative-Related Diseases of Human Ocular Surface Epithelium.Antioxidants (Basel, Switzerland) · 2021Article
- Interactions of Meibum and Tears with Mucomimetic Polymers: A Hint towards the Interplay between the Layers of the Tear Film.International journal of molecular sciences · 2021Article
- Evidence of Polyphenols Efficacy against Dry Eye Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Preparation and Evaluation of Starch Hydrogel/Contact Lens Composites as Epigallocatechin Gallate Delivery Systems for Inhibition of Bacterial Adhesion.Frontiers in bioengineering and biotechnology · 2021Article
- Epigallocatechin-3-gallate ameliorates LPS-induced inflammation by inhibiting the phosphorylation of Akt and ERK signaling molecules in rat H9c2 cells.Experimental and therapeutic medicine · 2020Article
- MucoadhesivePolymers · 2020Article
- Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride.Journal of ophthalmology · 2020Article
- Development of Kaempferol-Loaded Gelatin Nanoparticles for the Treatment of Corneal Neovascularization in Mice.Pharmaceutics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dry eye syndrome (DES) is a common eye disease. Artificial tears (AT) are used to treat DES, but they are not effective. In this study, we assessed the anti-inflammatory effect of AT containing epigallocatechin gallate (EGCG) and hyaluronic acid (HA) on DES. Human corneal epithelial cells (HCECs) were used in the WST-8 assay to determine the safe dose of EGCG. Lipopolysaccharide-stimulated HCECs showing inflammation were treated with EGCG/HA. The expression of IL-1ß, IL-6, IL-8, and TNF-α was assessed by real-time PCR and AT physical properties such as the viscosity, osmolarity, and pH were examined. AT containing EGCG and HA were topically administered in a rabbit DES model established by treatment with 0.1% benzalkonium chloride (BAC). Tear secretion was assessed and fluorescein, H&E, and TUNEL staining were performed. Inflammatory cytokine levels in the corneas were also examined. The non-toxic optimal concentration of EGCG used for the treatment of HCECs in vitro was 10 μg/mL. The expression of several inflammatory genes, including IL-1ß, IL-6, IL-8, and TNF-α, was significantly inhibited in inflamed HCECs treated with 10 μg/mL EGCG and 0.1% (w/v) HA (E10/HA) compared to that in inflamed HCECs treated with either EGCG or HA alone. AT containing E10/HA mimic human tears, with similar osmolarity and viscosity and a neutral pH. Fluorescence examination of the ocular surface of mouse eyes showed that HA increased drug retention on the ocular surface. Topical treatment of DES rabbits with AT plus E10/HA increased tear secretion, reduced corneal epithelial damage, and maintained the epithelial layers and stromal structure. Moreover, the corneas of the E10/HA-treated rabbits showed fewer apoptotic cells, lower inflammation, and decreased IL-6, IL-8, and TNF-α levels. In conclusion, we showed that AT plus E10/HA had anti-inflammatory and mucoadhesive properties when used as topical eye drops and were effective for treating DES in rabbits.
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