Oxidative Stress in Dry Eye Disease: Molecular Mechanisms and Emerging Therapeutic Strategies

Dry eye disease (DED) is a chronic inflammatory disorder of the ocular surface, characterized by tear film homeostasis imbalance, with aging being identified as a crucial independent risk factor. Oxidative stress, which refers to the excessive production of reactive oxygen species (ROS) and reactive nitrogen substances during mitochondrial metabolism and the weakened protective effect of antioxidants, plays a central role in this process. With aging, the mitochondrial function of ocular surface tissues, such as the corneal epithelium, meibomian glands, and lacrimal glands, declines. Concurrently, the activity of endogenous antioxidant enzymes (such as superoxide dismutase and glutathione peroxidase) decreases, and the levels of tear antioxidants such as lactoferrin also decrease. These age-related changes collectively lead to excessive accumulation of ROS, triggering oxidative stress that directly damages biomacromolecules in ocular surface cells and impairs the stability of the tear film. Furthermore, we have summarized the current therapeutic strategies for oxidative stress in DED, including both conventional antioxidants and emerging approaches such as eye drops based on nanoenzymes, thermosensitive hydrogels, intense pulsed light therapy, and drug-eluting contact lenses. By combining the new progress in the delivery systems of biomaterials-based drugs with mechanism-guided interventions, this review systematically establishes the intimate functional linkages between mitochondrial dysfunction, oxidative stress, and the pathogenesis of DED and focuses on elaborating the translational potential of advanced biomaterials-based antioxidant regimens, aiming to provide novel foundations and insights theoretical for the development of more effective and precise therapeutic strategies for DED.