ABSTRACT: Purpose: To establish a clinically relevant mouse model of contact lens–related dry eye (CLDE) and evaluate the therapeutic effects and potential mechanisms of the cationic nanoemulsion Cationorm®. Methods: CLDE was induced by combined benzalkonium chloride (BAC) exposure and daily contact lens wear. After model establishment, mice were treated with normal saline, hyaluronic acid (HA), or Cationorm®. Tear film stability, tear secretion, and corneal epithelial damage were assessed using tear breakup time, phenol red thread test, and corneal fluorescein staining. Corneal and meibomian gland morphology were evaluated by histology, apoptosis was assessed by TUNEL staining, and barrier- and inflammation-related gene expression was analyzed by RT-qPCR. RNA sequencing was performed to explore treatment-associated molecular pathways. Results: The BAC+CL model induced tear film instability, reduced tear secretion, corneal epithelial damage, barrier-related gene dysregulation, and ocular surface inflammation. Cationorm® significantly prolonged tear breakup time compared with saline and HA and partially improved tear secretion. Cationorm® reduced corneal epithelial damage, improved corneal epithelial morphology, and increased the expression of barrier-related genes, including Zo1 and Occludin. Inflammatory markers, including Il1b, Tnfa, and Mmp9, were reduced after Cationorm® treatment. Cationorm® also reduced apoptosis in the cornea and meibomian gland and preserved meibomian gland structure. Transcriptomic analysis revealed enrichment of epithelial junction–related and immune-related pathways associated with Cationorm® treatment. Conclusions: Cationorm® improves ocular surface abnormalities in a dual-hit CLDE mouse model through coordinated effects on tear film stability, corneal epithelial integrity, inflammation, apoptosis, and meibomian gland structure. These findings support its potential as a multi-target therapeutic strategy for CLDE.
