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.