Abstract
Idiopathic epiretinal membrane (iERM) is a pathological fibrocellular change in the vitreoretinal junction over the macular area; however, possible pathogenic mechanisms remain unclear. Changes in the differential protein composition of the aqueous humor (AH) may represent potential molecular changes associated with iERM. To gain new insights into the molecular mechanisms of iERM pathology, a sensitive label-free proteomics analysis was performed to compare AH protein expressions in patients with cataracts with or without iERM. This study employed nanoflow ultra-high-performance liquid chromatography-tandem mass spectrometry to investigate protein compositions of the AH obtained from individual human cataract eyes from 10 patients with iERM and 10 age-matched controls without iERM. Eight proteins were differentially expressed between the iERM and control samples, among which six proteins were upregulated and two were downregulated. A gene ontology (GO) analysis revealed that iERM was closely associated with several biological processes, such as immunity interactions, cell proliferation, and extracellular matrix remodeling. Additionally, multiple proteins, including lumican, cyclin-dependent kinase 13, and collagen alpha-3(VI) chain, were correlated with the central retinal thickness, indicating a multifactorial response in the pathogenic process of iERM. Changes in the AH level of lumican between iERM and control samples were also confirmed by an enzyme-linked immunosorbent assay. In conclusion, several pathological pathways involved in iERM were identified in the AH by a proteomic analysis, including immune reactions, cell proliferation, and remodeling of the extracellular matrix. Lumican is a potential aqueous biomarker for predicting iERM development and monitoring its progression. More clinical parameters also need to be identified to complete the analysis, and those could provide additional targets for treating and preventing iERM.