Single-Cell Transcriptomics Reveals Effects of Long-Term Contact Lens Wearing on the Human Corneal Epithelium

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Purpose: Corneal contact lenses (CLs) are increasingly used as a treatment for myopia correction. This study aimed to elucidate the molecular mechanisms underlying corneal epithelial pathological changes induced by long-term CL wear, thereby providing potential targets for the prevention and management of CL-related corneal complications. Methods: We initially conducted single-cell RNA sequencing on intact corneal epithelium samples obtained from myopic patients with prolonged CL wear and nonwearing controls. Differential expression analysis and functional enrichment systematically characterized cell type-specific transcriptional changes between the two groups. Additionally, gene set expression scoring analysis, combined with experimental validation, revealed distinct pathological signatures associated with long-term CL use. Results: Our analysis revealed a significant increase in epithelial keratinization and enhanced chronic inflammatory response in the CL group. All epithelial cell types exhibited elevated senescence scores following prolonged CL wear. Furthermore, we detected a significant upregulation of hypoxia-related genes in the corneal epithelium of CL wearers, accompanied by metabolic impairment and dysfunction. Moreover, most typical angiogenesis- and neurodegeneration-related genes showed significantly higher expression levels in the corneal epithelium after extended CL use. Conclusions: Long-term wear of CLs may induce various manifestations in corneal epithelial cells, including keratinization, inflammatory response, aerobic metabolic impairment, cellular senescence, neovascularization, and corneal sensory abnormalities. These changes could compromise ocular surface barrier function and increase the risk of infectious keratitis.

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