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Aqueous Humor Proteomic Analysis Identifies Diagnostic Biomarkers for Autoimmune Optic Neuritis

Year: 2026

Type: preprint

Abstract: Autoimmune optic neuritis (AON) is an inflammatory optic neuropathy that commonly presents with acute or subacute visual loss. In the early stage, AON may overlap clinically with other optic neuropathies, particularly non-arteritic anterior ischemic optic neuropathy (NAION). Although serum and cerebrospinal fluid biomarkers can provide diagnostic assistance, they do not directly reflect the local ocular microenvironment. In this study, aqueous humor (AH) was used as a local liquid biopsy source to identify candidate molecules associated with AON. Data-independent acquisition (DIA) proteomics was applied to analyze AH proteins obtained from patients with AON, patients with NAION, and presbyopic surgical controls (CTL group) during anterior chamber paracentesis or surgery. Candidate biomarkers were subsequently quantified by enzyme-linked immunosorbent assay (ELISA). Proteomic analysis identified 4,264 proteins from 18 samples. Gene Ontology annotation and functional analysis showed that AON-related biological processes were mainly associated with immune responses, ganglioside biosynthesis, glycoprotein biosynthesis, lysosomal function, and protein translation. Candidate protein selection integrated fold change, biological module relevance, protein-protein interaction (PPI) network centrality, and ELISA feasibility, leading to the selection of lactoferrin (LTF), ribosomal protein SA (RPSA), and ATPase H+ transporting V1 subunit A (ATP6V1A) for further validation. The results showed that LTF concentration differed significantly between the AON and CTL groups and demonstrated diagnostic utility in receiver operating characteristic analysis, suggesting that LTF may serve as a potential aqueous humor biomarker for AON. In contrast, RPSA and ATP6V1A did not show stable intergroup differences during validation; nevertheless, the protein translation stress and lysosome-related pathways represented by these molecules suggest corresponding functional alterations in the AH microenvironment of AON. Overall, this study provides an initial characterization of the AH proteomic profile in AON and indicates that AH proteomics may offer a new approach for elucidating local pathological mechanisms and identifying fluid-based diagnostic biomarkers for AON.

Source: Research Square

DOI: 10.21203/rs.3.rs-11055905/v1