Oxidative stress and mitochondrial dysfunction drive Dry Eye Disease progression, highlighting new therapeutic targets

Dry Eye Disease (DED) is a prevalent multifactorial ocular surface condition affecting approximately 11.59% globally, characterized by tear film instability and ocular surface damage. Current therapies primarily focus on symptom alleviation, often falling short in addressing the underlying pathology. Aging significantly increases DED prevalence, correlating with elevated oxidative stress and reduced endogenous antioxidants. This review explores how tear hyperosmolarity induces oxidative stress, and critically, how mitochondrial dysfunction acts as a central upstream factor in DED pathogenesis.

This comprehensive review systematically analyzed existing literature to elucidate the molecular mechanisms of oxidative stress in Dry Eye Disease (DED). The authors synthesized evidence linking tear film instability, hyperosmolarity, and mitochondrial dysfunction to the generation of reactive oxygen species (ROS) and subsequent ocular surface damage. The review also identified and discussed emerging therapeutic strategies that target these specific oxidative pathways, moving beyond conventional symptomatic treatments.

The review highlights that tear hyperosmolarity in Dry Eye Disease (DED) directly induces oxidative stress, disrupting electrolyte balance and damaging the ocular surface. A central finding is that mitochondrial dysfunction acts as a pivotal upstream driver, coordinating ROS production, cellular damage, and inflammatory cascades, thereby perpetuating the DED vicious cycle.

The interaction of tear hyperosmolarity, oxidative stress, and chronic inflammation propagates Dry Eye Disease into a vicious circle, with mitochondrial dysfunction identified as a central upstream driving factor. The authors detail how decreased endogenous antioxidants and increased ROS production, particularly with aging, exacerbate DED progression. This comprehensive understanding underscores the need for therapies that move beyond mere symptom alleviation to address the underlying oxidative and mitochondrial damage, offering a more holistic approach to DED management.