Cross-tissue dual-omics analysis reveals molecular programs linked to myopia susceptibility and progression

Myopia is a global cause of vision impairment, yet its molecular mechanisms remain unclear. We applied a multi-omics approach to the retina, choroid, and sclera of guinea pigs (GPs), a model of spontaneous myopia. Integrated transcriptomic and proteomic analyses suggest a two-state molecular framework. In a myopia-prone state, the choroid and sclera exhibited widespread transcript-protein discordance, with RNA and protein changes in remodeling pathways not aligned in direction, alongside metabolic down-regulation and suppressed immune transcription, a primed yet quiescent state preceding elongation. In a spontaneous myopic state, molecular regulation becomes more concordant, with RNA and protein changing in the same direction, indicating active remodeling, whereas ribosome/translation emerged as a consistent cross-tissue signal. Integration with human myopia GWAS loci, followed by validation of CYP26A1 expression in GP ocular tissues at both transcript and protein levels, highlighted post-transcriptional regulation in the sclera and underscored translational relevance. These findings provide a molecular framework for myopia development and nominate targets in neurogenesis, synaptic remodeling, and translational control for therapeutic intervention.