Abstract
BACKGROUND: Diabetic retinopathy (DR) is a progressive retinal disease that leads to vision loss if not detected early. Metabolomic analysis of vitreous humor offers a promising approach to identifying biomarkers associated with disease onset and progression. This pilot study investigates the metabolomic profiles of vitreous humor from patients at different stages of DR, aiming to uncover potential biomarkers for early detection and monitoring of disease progression. METHODS: Vitreous samples were collected during therapeutic pars plana vitrectomy of 23 patients without diabetes (CTRL), with diabetes and without retinopathy (DIA), non-proliferative DR (NPDR) and proliferative DR (PDR). Metabolomics was performed using high-performance liquid chromatography coupled with high-resolution mass spectrometry. RESULTS: Principal component analysis revealed distinct metabolic signatures differentiating the patient groups. Lysine, proline, and arginine levels progressively increased from DIA to NPDR and PDR stages, highlighting their association with disease progression. Methionine and threonine showed notable increases in PDR compared to all other groups, while carnitine, a key metabolite in lipid metabolism, exhibited stage-specific increases, peaking in PDR. The detection of systemic and topical drugs, including metformin and tropicamide, in the vitreous further emphasizes altered ocular permeability in DR. CONCLUSION: Our findings suggest that metabolomic profiling could provide valuable insights into the underlying pathogenesis of DR and serve as a foundation for personalized therapeutic strategies.