Vitreous proteomic insights into the pathogenesis of nonarteritic anterior ischemic optic neuropathy

Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic nerve injury and vision loss in older individuals. However, the pathogenesis of NAION remains poorly understood, and no treatment has conclusively demonstrated efficacy. This study aimed to explore and describe the proteome of the vitreous humor in eyes with NAION. Ten patients diagnosed with NAION and ten comparative controls diagnosed with idiopathic epiretinal membranes were enrolled in this study. The vitreous proteomes of both groups were analyzed using liquid chromatography-tandem mass spectrometry, and multiple reaction monitoring was performed to validate the target proteins. A total of 815 proteins were identified in both groups, of which 155 were common to both groups. Among these, 98 proteins were significantly upregulated and 57 proteins were downregulated in the NAION group compared to those in the controls. NAION is associated with the increased expression of proteins involved in hemostasis and metabolic pathways. Additionally, extracellular matrix (ECM) remodeling molecules were downregulated in the NAION vitreous, which likely reflects increased vitreous liquefaction and alterations in vitreous biomechanics. This study provides a comprehensive proteomic profile of the vitreous humor in eyes with NAION and highlights the dysregulation of hemostasis, metabolic pathways, and ECM remodeling. These findings enhance our understanding of the molecular mechanisms underlying NAION and may pave the way for the development of novel biomarkers and therapeutic targets.