Nano-alkaline ion-excited NETs ablative eye drops promote ocular surface recovery

Neutrophil extracellular traps (NETs) promote neovascularization during the acute phase after ocular chemical injury, while the local inflammatory acidic environment delays post-injury repair. Currently, the mechanism of NETs promoting neovascularization has not been fully elucidated, and there is a lack of therapeutic strategies to effectively improve the local microenvironment for corneal repair. In this study, we validated the NETs-M2-angiogenic pathway after injury. Using transcriptomics sequencing and liquid-phase microarray assays, the intrinsic immune cascade mechanism of NETs inducing macrophage M2 polarization and releasing VEGF via PI3K/AKT was identified. Based on this pathology and the physiological need to improve the local inflammatory acidic environment and promote corneal repair, we organically integrated the alkaline ion-rich bioglass with the highly transmissive and highly adhesive filipin protein, and constructed NETs ablative gel eye drops (DMS) that can release DNase I and alkaline ions in a sustained manner. The eye drops restricted the inflammatory interaction of NETs with macrophages from the source, adhered to the corneal surface and continuously released alkaline ions to improve the local acidic inflammatory environment, providing a favorable immune microenvironment for corneal recovery. We established a cell co-culture system and a corneal alkali burn model to further validate the role of DMS in modulating the intrinsic immune cascade of neovascularization for corneal repair and the related mechanisms. In conclusion, based on the biological mechanism of NETs-M2-VEGF after corneal chemical injury, the present study designed eye drops for dual regulation of intrinsic immunity and the inflammatory acid environment, which not only further supplemented and improved the pathophysiological mechanism of corneal neovascularization after chemical injury, but also provided a new way of thinking about corneal regeneration after injury.