The Effects of Fisetin on Cyclosporine-Treated Dry Eye Disease in Dogs

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 ± 6.02 mm, p = 0.47; 9.80 mm ± 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 ± 527.52 ng/mL, p = 0.05; 328.49 ng/mL ± 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.