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

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Myopia is a leading cause of vision impairment globally.
• The precise molecular mechanisms underlying myopia development are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms of myopia development using a multi-omics approach.
• To identify potential therapeutic targets for myopia intervention.

Main Methods:

• Integrated transcriptomic and proteomic analyses of retina, choroid, and sclera in guinea pigs (a model of spontaneous myopia).
• Analysis of myopia-prone and spontaneous myopic states.
• Integration with human myopia Genome-Wide Association Study (GWAS) loci.
• Validation of CYP26A1 expression.

Main Results:

• A two-state molecular framework for myopia development was identified.
• Transcript-protein discordance in remodeling pathways was observed in a myopia-prone state, with metabolic and immune suppression.
• Concordant molecular regulation and ribosome/translation activity characterized the spontaneous myopic state.
• Post-transcriptional regulation in the sclera and translational relevance were highlighted, with specific focus on CYP26A1.

Conclusions:

• The study provides a molecular framework for understanding myopia progression.
• Identified molecular signatures suggest potential therapeutic targets in neurogenesis, synaptic remodeling, and translational control.