Proteomic profiling of vitreous humor identifies downregulation of VASN and TNC in idiopathic macular hole

This study aime\d to characterize vitreous proteomic changes in idiopathic macular hole (IMH) and to investigate molecular distinctions from epiretinal membrane (ERM). A prospective study analyzing proteomics was conducted on undiluted vitreous samples from 10 IMH patients and 10 ERM controls of similar age. Label-free quantitative mass spectrometry integrating data-independent acquisition (DIA) workflows was used to identify differentially expressed proteins (DEPs). Bioinformatic analyses included Gene Ontology (GO) and KEGG pathway enrichment. Selected candidate proteins were validated by enzyme-linked immunosorbent assay (ELISA). A total of 826 vitreous proteins were quantified via DIA, with 19 showing differential expression (FDR-adjusted p < 0.05). Enrichment analyses suggested associations with extracellular matrix organization, cell adhesion, and signaling pathways related to glial activation and tissue remodeling. ELISA validation confirmed significantly reduced vitreous levels of VASN (p = 0.0024) and TNC (p = 0.0005) in IMH compared with ERM, whereas LAMC1 showed no significant difference (p = 0.43). Comparative vitreous proteomics identified consistent downregulation of VASN and TNC in IMH. These findings suggest that alterations in the vitreous microenvironment may be associated with dysregulated extracellular matrix and tissue remodeling processes in IMH. Further functional and larger scale studies are required to clarify their mechanistic and clinical relevance.