title: Synergistic Effect of Artificial Tears Containing Epigallocatechin Gallate and Hyaluronic Acid for the Treatment of Rabbits with Dry Eye Syndrome.
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.
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei City 110, Taiwan.
authors.forename: Ching-Li
authors.identifier: http://orcid.org/0000-0001-9446-4030
authors.initials: CL
authors.lastname: Tseng
authors.affiliation: Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No.1, Section 3, Chung-Hsiao E. Road, Taipei City 106, Taiwan.
authors.forename: Ya-Jung
authors.initials: YJ
authors.lastname: Hung
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei City 110, Taiwan.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No.1, Section 3, Chung-Hsiao E. Road, Taipei City 106, Taiwan.|Institute of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Taiwan, No. 35, Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan.
authors.forename: Hsu-Wei
authors.initials: HW
authors.lastname: Fang
authors.affiliation: Department of Ophthalmology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City 112, Taiwan.|Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei City 110, Taiwan.
authors.forename: Ko-Hua
authors.initials: KH
authors.lastname: Chen
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D018836:Inflammation Mediators; D065346:Lubricant Eye Drops / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D011817:Rabbits
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D065346:Lubricant Eye Drops; D002392:Catechin; D006820:Hyaluronic Acid; C045651:epigallocatechin gallate