Oxidative Stress and Uveitis: Molecular Mechanisms and Pathogenetic Role

Abstract

Uveitis comprises a heterogeneous group of intraocular inflammatory diseases that differ in anatomical location, etiology, clinical course, and immune mechanisms. Despite this diversity, evidence derived predominantly from experimental autoimmune uveitis (EAU) suggests that oxidative stress may act as a context-dependent amplifier linking immune activation, ocular barrier dysfunction, and tissue injury. Excess reactive oxygen species (ROS) disrupt redox homeostasis and activate redox-sensitive inflammatory signaling, thereby amplifying cytokine production, mitochondrial dysfunction, leukocyte recruitment, and retinal damage. This review summarizes current evidence on oxidative stress in uveitis, focusing on major ROS-generating systems, NF-κB-driven inflammation, Nrf2/HO-1-mediated antioxidant responses, MAPK and PI3K-Akt signaling, and immune–metabolic pathways involved in autoimmune ocular inflammation. Cell-specific responses in retinal and immune cells further illustrate how redox imbalance may contribute to local tissue injury and immune-mediated disease progression. The role of oxidative stress in blood–ocular barrier dysfunction, particularly blood–retinal barrier disruption during posterior segment inflammation, is also discussed. Overall, preclinical studies support an active role for oxidative stress in inflammatory amplification and ocular tissue injury, whereas evidence from patients with defined uveitic entities remains limited, heterogeneous, and largely associative. Redox-directed treatments should therefore currently be regarded as investigational adjunctive strategies rather than established therapies for uveitis.