Peptide DFCPPGFNTK Mitigates Dry Eye Pathophysiology by Suppressing Oxidative Stress, Apoptosis, Inflammation, and Autophagy: Evidence from In Vitro and In Vivo Models.

Dry eye is an ophthalmic disease with an intricate pathomechanism, and there are no effective interventions or medications available. We investigated the effects of a peptide, DFCPPGFNTK (DFC), screened from tilapia skin hydrolysate on dry eye and its underlying mechanisms. In vitro, human corneal epithelial cells (HCECs) were challenged by 100 mM NaCl in a hyperosmotic environment. DFC restored the cell viability of HCECs induced by NaCl, reduced the transition of mitochondrial membrane potential, delayed the apoptosis of damaged cells, reduced the production of reactive oxygen (ROS) and malondialdehyde (MDA), increased the activities of superoxide dismutase (SOD) and catalase (CAT), and increased the expression rate of Bcl-2/Bax. Compared to the model group, the protein expression levels of COX-2 and iNOS were down-regulated, the mRNA expression of Tnf-α and Il-6 were decreased, the protein expression levels of Nrf2 and HO-1 were increased, and the levels of autophagy-related proteins p62 and LC3B were regulated. In vivo, the dry eye model was developed by administering eye drops of 0.2% BAC to mice for 14 days. DFC increased tear secretion, changed the morphology of tear fern crystals, prevented corneal epithelial thinning, reduced the loss of conjunctival goblet cells (GCs), and inhibited the apoptosis of mice corneal epithelial cells. In summary, DFC improved dry eye by inhibiting oxidative stress, apoptosis, inflammation, and autophagy.