Abstract
Bisphenol A (BPA) is a widely utilized endocrine-disrupting chemical that has been associated with metabolic dysregulation in various tissues. Nevertheless, its impact on ocular metabolism remains insufficiently understood. This study aims to investigate the metabolic effects of BPA exposure in ARPE-19 retinal pigment epithelial cells using untargeted metabolomics. ARPE-19 cells were exposed to 100 µM BPA for 24 hours, and cytotoxicity, intracellular reactive oxygen species (ROS) levels and glutathione metabolism parameters were identified. Metabolic alterations were analyzed utilizing liquid chromatography-quadrupole time-of-flight mass spectrometry (Q-TOF LC/MS). Principal component analysis (PCA), volcano plots, heatmaps, and pathway enrichment analysis were conducted to identify significantly altered metabolites and pathways. BPA exposure led to notable metabolic changes, including alterations in the tricarboxylic acid (TCA) cycle, β-oxidation, nucleoside metabolism, and amino acid metabolism. Key metabolite changes included increased levels of glutamine, pyroglutamic acid, anserine, and adenosine 2',3'-cyclic phosphate, suggesting oxidative stress and metabolic adjustment. Pathway analysis identified significant changes in arachidonic acid metabolism and pyrimidine metabolism, indicating oxidative stress and metabolic compensation due to BPA exposure. The findings underscore the metabolic risks of BPA exposure to retinal health and necessitate further validation through targeted metabolomics and in vivo studies.