Oxidative Stress and Redox Imbalance in Acanthamoeba Keratitis: Host–Parasite Crosstalk and Therapeutic Perspectives

Acanthamoeba keratitis is a severe, sight-threatening corneal infection caused by free-living amoebae widely distributed in soil, natural waters, and domestic or recreational water systems. Following entry into the corneal microenvironment, disease develops within a redox conflict in which host-derived reactive oxygen species (ROS) and reactive nitrogen species (RNS) may contribute to parasite control while simultaneously promoting inflammation and tissue injury. Acanthamoeba responds through an adaptable defense network involving superoxide dismutases, catalase, thioredoxin- and glutathione-dependent systems, peroxiredoxins, and mitochondrial mechanisms. However, most mechanistic evidence derives from in vitro trophozoite studies, whereas the contribution of individual redox pathways to mature cyst survival and persistence in the infected cornea remains poorly defined. This review critically integrates evidence on host oxidative and nitrosative responses, parasite antioxidant adaptation, bidirectional redox crosstalk, and redox-modulating therapeutic strategies. Current data support neither indiscriminate suppression nor uncontrolled amplification of reactive species. Instead, future interventions should achieve spatially, temporally, and stage-specifically controlled redox modulation that weakens parasite defenses while preserving corneal integrity and essential innate immune functions. Progress will require causal validation of redox targets, separate assessment of trophozoites and mature cysts, long-term excystation and regrowth assays, evaluation across clinical isolates and genotypes, and parallel assessment of host-cell toxicity in clinically relevant corneal models.