Melatonin Ameliorates Desiccation Stress-Induced Ocular Inflammation in an In Vitro Model by Activating the Nrf2 Pathway.

Dry eye disease (DED) is a multifactorial ocular disorder marked by tear film instability, oxidative stress, and inflammation. Although melatonin is known to exert antioxidant and anti-inflammatory effects, its precise role in regulating desiccation-induced stress responses at the ocular surface has not been well defined. In particular, the involvement of the Nrf2 signalling pathway in melatonin-mediated protection against corneal epithelial inflammation under tear film instability remains unexplored. In this study, we evaluated the therapeutic potential of melatonin in a human corneal epithelial cell (HCEC) model mimicking desiccation stress. Melatonin treatment significantly reduced reactive oxygen species (ROS) levels and upregulated antioxidant enzymes, including catalase (CAT) and heme oxygenase-1 (HO-1), via Nrf2 pathway activation. These effects were attenuated by Nrf2 knockdown using siRNA, confirming pathway specificity. Furthermore, melatonin markedly suppressed pro-inflammatory cytokine production, suggesting a dual mechanism of action involving both redox regulation and immune modulation. Our findings provide novel insight into the Nrf2-dependent effects of melatonin on ocular surface protection under desiccation conditions. These results suggest melatonin as a promising candidate for the treatment of DED through simultaneous modulation of oxidative and inflammatory pathways specific to tear film instability.