Tilapia Skin Peptides Inhibit Apoptosis, Inflammation, and Oxidative Stress to Improve Dry Eye Disease In Vitro and In Vivo

Abstract

Dry eye disease (DED) is a common chronic ophthalmic disorder, and there is no effective treatment to cure it. It is urgent to find new antidry eye compounds. Here, the effects and underlying mechanisms of tilapia skin peptides (TSP) on DED were investigated. In vitro, human corneal epithelial cells (HCECs) were cultured in a hypertonic medium containing TSP for 12 h. The MTT assay, calcein-AM/PI staining, reactive oxygen (ROS) analysis, and western blot were performed at the end of the experiments. In the in vivo model of DED, mice eyes were dropped with 0.3% benzalkonium chloride (BAC) and 0.1% TSP for 14 days. Mice were treated with BAC and TSP twice daily with a 10-hour time interval between treatments. After treatment, phenolic red cotton experiment, tear ferning test, and histology assay were carried out. In vitro, TSP significantly restored the cell viability of HCECs challenged by NaCl. In vivo, tear secretion function and tear fern-like crystal levels were considerably improved in the DED group after treatment with TSP. Mechanically, TSP impend the DED development by regulating Bax/Bcl-2 signal pathway, inhibiting iNOS and COX-2 protein expression, moderating ROS/Nrf2/HO-1 axis, inhibiting cell apoptosis in the corneal regions, increasing the number of conjunctival goblet cells, and arresting corneal epithelial thinning. In conclusion, TSP ameliorated DED-like disorder in BAC-induced DED mice and cell damage in NaCl-induced HCECs. TSP improved DED by suppressing apoptosis, inflammation, and oxidative stress. Consequently, this study reveals the beneficial activity of TSP in DED.