Metabolomic analysis of the aqueous humor from patients with central retinal vein occlusion using UHPLC-MS/MS

Abstract

Central retinal vein occlusion (CRVO) is one of the retinal fundus diseases and may result in irreversible visual impairment. Metabolic dysfunction has been proved to play an essential role in the pathogenesis of CRVO. We performed untargeted metabolomic analysis of the aqueous humor (AH) of patients with CRVO and controls using UHPLC-MS/MS.A total of 248 metabolites were identified in the tested AH samples, 37 of which allowed for the construction of an orthogonal partial least squares discriminant analysis model with good predictive capability (Q2cum = 0.834) and low risk of overfitting. The components contributing the most to the metabolomic signature of CRVO were those related to amino acid metabolism, carbohydrates, and fatty acid metabolites (variable importance on projection>1.0 and p < 0.05). The CRVO group appeared to have a lower AH concentration of carbohydrates and amino acids, but a relative higher concentration of carnitine-associated energetic substrates (butyryl carnitine, deoxycarnitine, N6-trimethyl-l-lysine) and osmolytes compared with those of the control group.These results indicate that patients with CRVO may have ocular aberrations in metabolic pathways involving certain amino acids, fatty acids, and carbohydrates. These metabolite changes might correlate with energy dysfunction and inflammation response in the AH of CRVO patients. This finding may provide insight into the pathophysiology of CRVO for the development of new therapeutic strategies.