Systematic review and meta-analysis of mass spectrometry proteomics applied to ocular fluids to assess potential biomarkers of age-related macular degeneration

Abstract

Abstract Background Age-related macular degeneration (AMD) is a significant cause of severe vision loss. The main purpose of this study was to identify mass spectrometry proteomics-based potential biomarkers of AMD that contribute to understanding the mechanisms of disease and aiding in early diagnosis. Methods This study retrieved studies that aim to detect differences relate to proteomics in AMD patients and healthy control groups by mass spectrometry (MS) proteomics approaches. The search process was accord with PRISMA guidelines (PROSPERO database: CRD42023388093). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes Pathway Analysis (KEGG) were performed on differentially expressed proteins (DEPs) in the included articles using the DAVID database. DEPs were included in a meta-analysis when their effect size could be computed in at least two research studies. The effect size of measured proteins was transformed to the log2-fold change. Protein‒protein interaction (PPI) analysis was conducted on proteins that were statistically significant in the meta-analysis using the String online database. Results Eleven studies fulfilled the inclusion criteria, and 161 DEPs were identified. The GO analysis showed that AMD is significantly related to proteolysis, extracellular exosome and protein binding. In KEGG, the most significant pathway was the complement and coagulation cascades. Meta-analysis results suggested that eight proteins were statistically significant, and according to PPI results, the most significant four proteins were serotransferrin (TF), apolipoprotein A1 (APOA1), complement C3 (C3) and lipocalin-1 (LCN1). Conclusions Four possible biomarkers, TF, APOA1, C3 and LCN1, were found to be significant in the pathogenesis of AMD and need to be further validated. Further studies should be performed to evaluate diagnostic and therapeutic value of these proteins.