Integrated genomics reveals cellular senescence-driven molecular networks and immune crosstalk in myopia pathogenesis.

Myopia, a leading global health challenge linked to severe ocular complications, remains poorly understood in terms of molecular mechanisms involving cellular senescence. This study integrates transcriptomic datasets (GSE112155 and GSE151631) from myopia and normal vision samples to unravel senescence-driven pathways and immune interactions underlying myopia pathogenesis. By constructing protein-protein interaction networks and post-transcriptional regulatory axes (mRNA-miRNA-TF), we identified core senescence-associated genes (Tp53, Cdkn1a, and Myc) as central regulators in myopia progression. Single-sample gene set enrichment analysis revealed significant immune dysregulation in myopia, marked by altered infiltration of γδ T cells, natural killer T cells, and neutrophils. Functional validation through Tp53 overexpression and Cdkn1a/Myc knockout in mice demonstrated their critical roles in exacerbating myopia phenotypes, including elongated eye axis and thickened retina. These findings highlight a synergistic interplay between cellular senescence and immune-mediated mechanisms in myopia, supported by multi-omics evidence and in vivo experiments. Our work not only maps the molecular networks bridging senescence and myopia but also proposes novel therapeutic targets for modulating these pathways. This study advances the understanding of myopia as a senescence-associated disorder and underscores the potential of targeting immune-senescence crosstalk for intervention.