{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:28:53Z","timestamp":1790389733091,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science, Research, and Sport of the Slovak Republic","award":["VEGA 1\/0333\/20"],"award-info":[{"award-number":["VEGA 1\/0333\/20"]}]},{"name":"Ministry of Education, Science, Research, and Sport of the Slovak Republic","award":["VEGA 1\/0194\/22"],"award-info":[{"award-number":["VEGA 1\/0194\/22"]}]},{"name":"Ministry of Education, Science, Research, and Sport of the Slovak Republic","award":["APVV-20-0324"],"award-info":[{"award-number":["APVV-20-0324"]}]},{"name":"Ministry of Education, Science, Research, and Sport of the Slovak Republic","award":["APVV-20-0528"],"award-info":[{"award-number":["APVV-20-0528"]}]},{"name":"Slovak Research and Development Agency","award":["VEGA 1\/0333\/20"],"award-info":[{"award-number":["VEGA 1\/0333\/20"]}]},{"name":"Slovak Research and Development Agency","award":["VEGA 1\/0194\/22"],"award-info":[{"award-number":["VEGA 1\/0194\/22"]}]},{"name":"Slovak Research and Development Agency","award":["APVV-20-0324"],"award-info":[{"award-number":["APVV-20-0324"]}]},{"name":"Slovak Research and Development Agency","award":["APVV-20-0528"],"award-info":[{"award-number":["APVV-20-0528"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry eye disease (DED) is a chronic debilitating ophthalmological disease with the current therapeutic options focused on the suppression of the symptoms. Among the possibilities of how to improve DED therapy, polyphenols have shown an enormous capacity to counteract DED functional changes. The study aimed to specifically target pathophysiological mechanisms by the addition of fisetin to the cyclosporine treatment protocol. We examined dog patients with DED on cyclosporine treatment that were administered 0.1% fisetin or fisetin-free eye drops. For the assessment of fisetin effects, tear film production and matrix metalloproteinase 9 (MMP-9) were studied in the tear film. Tear production was not recovered after 7 or 14 days (9.40 mm \u00b1 6.02 mm, p = 0.47; 9.80 mm \u00b1 6.83 mm, p = 0.53, respectively). MMP-9 levels significantly increased after 7 days and then dropped after 14 days (775.44 ng\/mL \u00b1 527.52 ng\/mL, p = 0.05; 328.49 ng\/mL \u00b1 376.29 ng\/mL, p = 1.00, respectively). Fisetin addition to cyclosporine DED treatment was not able to restore tear fluid production but influenced molecular pathological events through MMP-9.<\/jats:p>","DOI":"10.3390\/ijms24021488","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T03:47:01Z","timestamp":1673495221000},"page":"1488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Effects of Fisetin on Cyclosporine-Treated Dry Eye Disease in Dogs"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5312-7329","authenticated-orcid":false,"given":"Krist\u00edna","family":"Kraj\u010d\u00edkov\u00e1","sequence":"first","affiliation":[{"name":"Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Balicka","sequence":"additional","affiliation":[{"name":"Small Animal Clinic, University Veterinary Hospital, University of Veterinary Medicine and Pharmacy in Ko\u0161ice, Komensk\u00e9ho 73, 041 81 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria","family":"Lap\u0161ansk\u00e1","sequence":"additional","affiliation":[{"name":"Small Animal Clinic, University Veterinary Hospital, University of Veterinary Medicine and Pharmacy in Ko\u0161ice, Komensk\u00e9ho 73, 041 81 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Trbolov\u00e1","sequence":"additional","affiliation":[{"name":"Small Animal Clinic, University Veterinary Hospital, University of Veterinary Medicine and Pharmacy in Ko\u0161ice, Komensk\u00e9ho 73, 041 81 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8206-8476","authenticated-orcid":false,"given":"Zuzana","family":"Gu\u013ea\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Trieda SNP 1, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Kondrakhova","sequence":"additional","affiliation":[{"name":"Institute of Physics, Department of Condensed Matter Physics, Faculty of Science, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Park Angelinum 9, 041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladim\u00edr","family":"Komanick\u00fd","sequence":"additional","affiliation":[{"name":"Institute of Physics, Department of Condensed Matter Physics, Faculty of Science, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Park Angelinum 9, 041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Ra\u0161iov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladim\u00edra","family":"Tome\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, 040 11 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. 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