Proteomic Profiling Reveals ANGPTL7 Elevation in Aqueous Humor Linked to Intraocular Pressure Dysregulation in High Myopia

High myopia (HM) poses vision risks due to complications. This study used an integrative multiomics approach─Olink proteomics on aqueous humor (92 proteins) and transcriptomics on lens capsules─in 5 highly myopic cataract (HMC) and 6 age-related cataract (CON) patients. Proteomics identified 10 upregulated proteins in the HMC aqueous humor. Cross-referencing transcriptomics uniquely pinpointed ANGPTL7 as consistently elevated. Clinical validation in 43 patients (24 HMC vs 19 CON) showed significant positive correlations between aqueous ANGPTL7 levels and intraocular pressure (IOP) dynamics (baseline IOP and postoperative spikes) exclusively in the HMC group. Further analysis localized ANGPTL7 overexpression to the trabecular meshwork, coinciding with collagen-enriched extracellular remodeling and coregulation with METRNL. Elevated trabecular ANGPTL7 was confirmed in defocus-induced HM mice. These findings establish ANGPTL7 as a predictive biomarker and pathogenic mediator of HM-related IOP dysregulation, mechanistically linking axial-elongation-induced stress to aqueous outflow resistance. This microliter-scale multiomics integration provides a framework for surgical risk stratification and potential targeted therapies.