Abstract
Purpose :
Congenital Cataract (CC) is a blinding disease in children with extensive phenotypic heterogeneity and multiple mechanisms. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with CC, and identify the underlying pathogenesis.
Methods :
Metabolomic profiles of AH were analyzed and compared between CC patients (n=35 [19 interior cataract, 16 posterior cataract]) and age-related cataract patients without metabolic diseases as controls (n=30), using global untargeted metabolomics with ultra-high-performance liquid chromatography tandem mass spectrometry. Principal component analysis, partial least squares discriminant analysis and heat map were applied to demonstrate metabolomic characteristics. Pathway analysis was conducted using Kyoto Encyclopedia of Genes and Genomes. Receiver-operating characteristic (ROC) analyses were employed to select potential biomarkers.
Results :
A total of 318 metabolites were measured, and 50 significantly differential metabolites were identified between CC group and control group (VIP > 1.0, fold change > 1.5 or < 0.667 and P < 0.05). Amino acids, peptides, and analogues was the most abundant categories of differential metabolites. With 5-HIAA, L-Kynurenine, and N-Formylkynurenine significantly increased and showed intercorrelations, pathway enrichment analysis pointed to the tryptophan metabolism, which can regulate physiological functions including inflammation and immune responses. The ROC analysis implied 15 metabolites served as potential biomarkers in AH of CC patients (all AUC > 0.900). For subgroup analysis in CC, 6 metabolites were significantly changed in interior cataracts compared with posterior cataracts, including spermidine, calcitriol, ornithine, mevalonic acid, etc (VIP > 1.0, fold change > 1.2 or < 0.833 and P < 0.05). Three metabolic pathways were identified, including terpenoid backbone biosynthesis, ferroptosis, and endocrine and other factor-regulated calcium reabsorption.
Conclusions :
These results illustrated novel potential metabolites and metabolic pathways in CC, which provides new insights into the pathophysiology of CC.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.