Integration of Vitreous Lipidomics and Metabolomics for Comprehensive Understanding of the Pathogenesis of Proliferative Diabetic Retinopathy

As a vision-threatening complication of diabetes mellitus(DM),proliferative diabetic retinopathy (PDR) is associated with sustainedmetabolic disorders. Herein, we collected the vitreous cavity fluidof 49 patients with PDR and 23 control subjects without DM for metabolomicsand lipidomics analyses. Multivariate statistical methods were performedto explore relationships between samples. For each group of metabolites,gene set variation analysis scores were generated, and we constructeda lipid network by using weighted gene co-expression network analysis.The association between lipid co-expression modules and metaboliteset scores was investigated using the two-way orthogonal partial leastsquares (O2PLS) model. A total of 390 lipids and 314 metabolites wereidentified. Multivariate statistical analysis revealed significantvitreous metabolic and lipid differences between PDR and controls.Pathway analysis showed that 8 metabolic processes might be associatedwith the development of PDR, and 14 lipid species were found to bealtered in PDR patients. Combining metabolomics and lipidomics, weidentified fatty acid desaturase 2 (FADS2) as an important potentialcontributor to the pathogenesis of PDR. Collectively, this study integratesvitreous metabolomics and lipidomics to comprehensively unravel metabolicdysregulation and identifies genetic variants associated with alteredlipid species in the mechanistic pathways for PDR.