Alleviation of dry eye disease by Silurus asotus hydrolysate through anti-inflammatory, antioxidant and anti-apoptotic mechanisms
摘要
Dry eye disease (DED) is a multifactorial ocular disorder characterized by instability of tear film and inflammation. Although therapeutic options are available, improved, safe, and effective treatments and elucidation of underlying mechanisms are still required. This study aimed to evaluate the protective effects and underlying mechanisms of action of Silurus asotus protein hydrolysate (SAH) using in vitro and in vivo models of DED. A cell-based DED model was established by air-drying human corneal epithelial cells for 1.5 min, and they were SAH pretreated with SAH before induction of DED. The in vivo DED model was generated by topical administration of atropine sulfate in Sprague-Dawley rats. SAH was administered orally for two weeks. Tear secretion was measured using the phenol red thread test. Histological, immunohistochemical, and biochemical analyses were performed to assess structural and molecular changes in the cornea, retina, conjunctiva and lacrimal glands. SAH administration restored tear secretion and improved structural integrity of ocular tissues in rats with DED. Treatment with SAH markedly suppressed immune cell infiltration and significantly downregulated the expression of cluster of differentiation (CD) 3, CD4, adhesion molecules, and inflammasome-related factors. Moreover, SAH inhibited phosphorylation of extracellular signal-regulated kinase and reduced expression of matrix metalloproteinases, andalleviated oxidative stress and apoptosis by decreasing the levels of pro-apoptotic proteins. The high-dose SAH group exhibited superior efficacy in reducing inflammation, oxidative stress, and apoptosis compared to the low-dose group. These findings demonstrate that SAH effectively protects ocular tissues in both cellular and animal models of DED.