Dysregulation of human corneal miRNAs and their cognate targets in Fusarium spp. keratitis and its implication in disease progression.

PURPOSE: Fusarium spp. keratitis causes significant corneal blindness and often responds poorly to antifungal therapy. Understanding its pathogenesis is critical for improving disease management. In this context, dysregulated microRNAs are emerging as key modulators of host immune responses and corneal damage. This study aimed to characterize the dysregulation of human corneal miRNAs and their cognate targets during Fusarium spp. keratitis and to examine their association with disease progression, severity, and clinical outcome, including their diagnostic and prognostic potential.

METHODS

Corneal swabs and tissues were collected at presentation, after antifungal therapy, and post-therapeutic penetrating keratoplasty in non-responders, alongside cadaveric controls. Small RNA sequencing identified differentially expressed miRNAs at each stage. Functional enrichment and network analyses were conducted. Seventeen miRNAs were validated by RT-qPCR in 10 samples per group, followed by receiver operating characteristic (ROC) analysis in 20 additional samples to determine prognostic accuracy.

RESULTS

Distinct miRNA dysregulation occurred across Fusarium spp. keratitis stages. Enrichment analyses revealed involvement of inflammatory pathways, including IL-17, TNF, NF-kappaB, and Toll-like receptor signalling, regulated by miRNAs such as miR-149-5p, miR-184, and miR-328-3p. Downregulation of TGF-β signalling and WNT signalling mediated by miR-16-5p and miR-19a-3p was linked to impaired wound healing in non-responders. RT-qPCR confirmed significant expression changes with strong concordance to sequencing data. ROC analysis identified miR-19a-3p and miR-16-5p as robust prognostic markers across disease stages.

CONCLUSION

This study reveals miRNA-mediated mechanisms contributing to Fusarium spp. keratitis pathogenesis. miR-19a-3p and miR-16-5p are promising prognostic biomarkers for severity and treatment response, supporting their relevance for future clinical stratification studies.