Abstract
PURPOSE: Advances in mass spectrometry have provided new insights into the role of metabolomics in the etiology of several diseases. Studies on retinopathy of prematurity (ROP), for example, overlooked the role of metabolic alterations in disease development. We employed comprehensive metabolic profiling and gold-standard metabolic analysis to explore major metabolites and metabolic pathways, which were significantly affected in early stages of pathogenesis toward ROP. METHODS: This was a multicenter, retrospective, matched-pair, case-control study. We collected plasma from 57 ROP cases and 57 strictly matched non-ROP controls. Non-targeted ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was used to detect the metabolites. Machine learning was employed to reveal the most affected metabolites and pathways in ROP development. RESULTS: Compared with non-ROP controls, we found a significant metabolic perturbation in the plasma of ROP cases, which featured an increase in the levels of lipids, nucleotides, and carbohydrate metabolites and lower levels of peptides. Machine leaning enabled us to distinguish a cluster of metabolic pathways (glycometabolism, redox homeostasis, lipid metabolism, and arginine pathway) were strongly correlated with the development of ROP. Moreover, the severity of ROP was associated with the levels of creatinine and ribitol; also, overactivity of aerobic glycolysis and lipid metabolism was noted in the metabolic profile of ROP. CONCLUSIONS: The results suggest a strong correlation between metabolic profiling and retinal neovascularization in ROP pathogenesis. These findings provide an insight into the identification of novel metabolic biomarkers for the diagnosis and prevention of ROP, but the clinical significance requires further validation.