Metabolomic Profiling of Vitreous Humor Reveals Distinct Metabolic Signatures in Proliferative Vitreoretinopathy

Purpose: Proliferative vitreoretinopathy (PVR) remains associated with a poor prognosis despite advances in vitreoretinal surgery. In the absence of effective adjunctive therapies, this study aimed to characterize vitreous metabolic alterations in PVR to better understand its pathophysiology. Methods: Untargeted metabolomic profiling was conducted on vitreous humor samples from 38 eyes that underwent surgery: PVR (grade C, n = 10), rhegmatogenous retinal detachment (RRD; grades A and B, n = 18), and controls undergoing intraocular lens (IOL) scleral fixation (n = 10). Metabolites were analyzed using capillary electrophoresis-mass spectrometry. Metabolic profiles were compared pairwise among the three groups with multiple testing correction, and pathway enrichment analysis was performed. Results: RRD demonstrated no disease-specific metabolic signature relative to controls after multiple testing correction. In contrast, PVR exhibited a distinct metabolic profile compared with both RRD and controls. Pathway enrichment analysis revealed upregulation of amino acid and nitrogen metabolism-including arginine and proline metabolism, glycine and serine metabolism, the urea cycle, ammonia recycling, alanine metabolism, and the malate-aspartate shuttle-consistent with increased biosynthetic demand. Pathways related to fibrosis and stress responses were also enriched. Conclusions: This study shows that PVR exhibits a unique metabolic signature distinct from RRD, characterized by the activation of metabolic pathways that support increased energy demand, cellular proliferation, stress responses, and fibrotic remodeling. These findings provide insights into the metabolic mechanisms associated with the progression from RRD to PVR, suggesting potential therapeutic targets to prevent fibrosis and aberrant cell proliferation.