Abstract
PURPOSE: To compare the lipid profiles of vitreous humor (VH) obtained from patients with proliferative diabetic retinopathy (PDR) and healthy controls and to determine possible metabolic pathways associated with PDR. METHODS: VH samples from both PDR patients (PDR group) and healthy subjects (Control group) were harvested for lipid analysis using high-throughput liquid chromatography tandem mass spectrometry (LC-MS/MS). The differential expressions of lipids between the control and PDR groups were determined by both univariate and multivariate methods. The sensitivity and specificity of the differentially expressed lipids as the candidate biomarkers for DR were determined through the area under receiver operating characteristic (ROC) analysis. MetaboAnalyst 5.0 was used for metabolic pathway analysis. RESULTS: Lipids were abundant in the VH samples, and LC-MS/MS analysis identified 35 lipid classes, 849 lipid species from both groups. There were much higher total lipid levels in the VH derived from PDR patients than that in the controls and the levels of cholesteryl Ester (ChE), phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylinositol (PI), and sphingomyelin (SM) obviously increased in the PDR patients as compared with the controls (all p < 0.01). Of these lipid species, a total of 256 lipids (245 upregulated and 11 downregulated) were determined by combining univariate and multivariate statistical analyses. ROC analysis showed the selected differentially expressed lipids had an area under ROC greater than 0.8, exhibiting good diagnostic value in distinguishing PDR patients from the controls. Pathway analysis showed that these differentially expressed lipids were mainly enriched in sphingolipid and purine metabolic pathways. CONCLUSION: Differentially expressed lipids in the VH of PDR patients were shown as ideal candidate metabolic biomarkers for clinical diagnosis and prognosis of DR, shedding new light on the metabolic mechanism of DR. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-025-04347-7.