Vitamin C enhances corneal fungal infection treatment in mice via chemotaxis and anti-inflammation

Fungal keratitis (FK) is a persistent and vision-threatening disease. The potential of vitamin C (VC) in tissue protection is well-recognized; however, its specific role in FK and its interaction with antifungal drugs are not well defined. In this study, we investigated the role of VC in FK <i>in vitro</i> and <i>in vivo</i>. It revealed that VC substantially decreases clinical scores and corneal perforation rates in a murine model of FK. VC promoted a concentration-dependent increase in neutrophil infiltration via mast cells <i>in vitro</i> and confirmed this effect in <i>in vivo</i> experiments. Moreover, VC enhanced fungicidal activity by boosting infiltrated neutrophils, without influencing reactive oxygen species (ROS) production or neutrophil extracellular traps (NETs) formation. VC also mitigated the cytokine storm within bone marrow-derived macrophages and increased neutrophil apoptosis, thereby facilitating the efficient clearance of senescent neutrophils. The combination of VC with amphotericin B (AmB) demonstrated additive antifungal effects, reducing fungal load and corneal perforation. These results indicate that VC is pivotal in defending against fungal corneal infections by promoting neutrophil chemotaxis through mast cells (MCs) and modulating the inflammatory response, without suppressing neutrophils' antifungal capability. The combination of VC with AmB may present a new therapeutic avenue for FK.