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

## TL;DR

Vitamin C helps treat fungal eye infections in mice by improving immune cell movement and reducing inflammation, and works well with antifungal drugs.

## Contribution

Vitamin C's role in enhancing neutrophil chemotaxis and anti-inflammatory effects in fungal keratitis is newly demonstrated.

## Key findings

- Vitamin C reduces corneal perforation and clinical scores in a murine model of fungal keratitis.
- Vitamin C promotes neutrophil infiltration via mast cells and enhances fungicidal activity without affecting ROS or NETs.
- Combining vitamin C with amphotericin B shows additive antifungal effects and reduces fungal load.

## Abstract

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 in vitro and in vivo. 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 in vitro and confirmed this effect in in vivo 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.