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

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. 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. 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. 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.