92-Plex Inflammatory Proteomic Signatures in Aqueous Humor of High Myopia and Candidate Biomarkers

Objective: In this exploratory study with a limited sample size, we aimed to investigate inflammation-related proteins in the aqueous humor of high myopia (HM) patients, analyze their correlations with ocular parameters, and screen for potential biomarkers. Methods: 20 age-related cataract patients undergoing surgery (Jan 1, 2025 - Feb 1, 2026) were enrolled: HM group (n=12) and non-HM control (n=8). Aqueous humor was collected preoperatively; 92 inflammation-related proteins were quantified using Olink Target 96 Inflammation Panel. Differential expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network analysis, and Spearman correlation analysis were performed to explore the biological functions of differentially expressed proteins and their relationships with ocular parameters. Results: Nine differentially expressed proteins (DEPs) (FDR q<0.05, |log2FC|>0.585) were upregulated in HM vs control, most prominently HGF, CST5, CCL19. Enrichment analyses revealed that the DEPs were mainly enriched in the cytokine-cytokine receptor interaction pathway, chemokine signaling pathway, and immune-inflammatory response-related terms. PPI network analysis identified TWEAK, CXCL5, and CCL19 as core proteins. Exploratory correlation analysis identified several associations of nominal significance (uncorrected p < 0.05) between cytokines and ocular parameters in both HM and non-HM groups (eg, DNER and TWEAK with central corneal thickness, CXCL5 with macular center thickness; HGF with keratometry, spherical equivalent, and axial length; CST5 with macular thickness; TWEAK with choroidal thickness). However, none remained significant after FDR correction for multiple comparisons (all q > 0.25). These findings are considered hypothesis-generating. Conclusion: The upregulation of HGF, CST5, CCL19, TWEAK, CXCL5, and DNER in the aqueous humor of patients with high myopia and their specific correlations with ocular parameters suggest a new molecular perspective for understanding the pathogenesis of high myopia. These preliminary findings suggest that the candidate biomarkers may have potential relevance to high myopia progression; however, independent validation in larger cohorts is needed.