Novel Biomarkers for Screening Retinal Detachment Associated with Choroidal Detachment Using DIA-MS-Based Proteomics.

Abstract

Purpose: Rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) is known for its rapid progression and poor prognosis, making it a subject of significant clinical interest due to its complex pathogenesis. This study aims to utilize mass spectrometry for proteomic analysis of vitreous humor to identify proteins and biomarkers critical to the pathophysiology of RRDCD.

Methods: Data-independent acquisition (DIA) mass spectrometry was employed to analyze vitreous humor samples from RRDCD and Rhegmatogenous retinal detachment (RRD) patients. The analysis focused on identifying differentially expressed proteins (DEPs) and determining their functional roles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the biological processes and pathways associated with these DEPs. DEPs were validated using ELISA to confirm the reliability of the mass spectrometry results.

Results: A total of 237 DEPs were identified, including 63 upregulated and 174 downregulated proteins. GO functional analysis showed enrichment in terms related to molecular function regulators, biological adhesion, and the extracellular region. KEGG pathway analysis revealed significant associations with the Extracellular environment (ECM)-receptor interaction, complement and coagulation cascades, and lysosome pathways. Receiver operating characteristic (ROC) analysis further confirmed that Serum amyloid A-4 protein (SAA4), Inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1), and Vitronectin (VTN) exhibit excellent performance in the diagnosis of RRDCD. Both VTN and SAA4 showed positive correlations with BCVA at 6 months post-surgery.

Conclusion: RRDCD activates a variety of cellular pathways, not only complement and inflammation, but also the remodeling of the extracellular matrix and the activation of lysosome-related pathways disrupt normal retinal cell function. SAA4, ITIH1, and VTN in vitreous fluid can serve as effective biomarkers for diagnosing patients with RRDCD. Additionally, both VTN and SAA4 are correlated with post-operative visual outcomes.