Pediatric cataract presents at birth or during early childhood, and is the main cause of childhood blindness worldwide [Zhao and Zhao, 2021]. Performing surgery to relieve form deprivation is the recommended treatment to promote visual rehabilitation [Singh et al., 2022]. However, postoperative complications including visual axis opacification, glaucoma, retinal detachment, provide different challenges to the visual prognosis in children [Singh et al., 2022]. Therefore, research has been concentrating on investigating the molecular etiology of pediatric cataract [Bell et al., 2020; Pichi et al., 2016; Taylan Şekeroğlu and Utine, 2021], which may help to discover therapeutic targets to slow or even reverse lens opacification.

Researches have explored etiological mechanisms associated with pediatric cataract based on genes and aggregation of mutant proteins, while rare literatures focus on the role of metabolism. Mutations causing congenital cataract were generally categorized as crystallin mutations, lens membrane protein mutations, lens cytoskeletal element mutations, developmental regulatory gene mutations [Bell et al., 2020; Taylan Şekeroğlu and Utine, 2021]. A few abnormal changes of metabolites, such as accumulation of cholesterol or galactose, were suggested to be related to pediatric cataract features in systemic diseases [Bell et al., 2020]. However, metabolic mechanism of pediatric cataract remains unknown.

Aqueous humor (AH) can supply nutrients and metabolites to the eye lens, which are essential for the proper functioning of lens [Yanshole et al., 2019]. AH of congenital cataract patients has been assessed for cytokine profiles and inflammatory factors using multiplex enzyme-linked immunosorbent assays and Luminex xMAP technology [Sauer et al., 2016; Wu et al., 2018; Zhang et al., 2020]. Metabolomics is a promising approach for the exploration of disease pathogenesis [Haines et al., 2018], as metabolites can accurately reflect the physiological changes with the role of downstream products of gene transcription, translation, and post-translational protein modification [Baharum and Azizan, 2018; Oldiges et al., 2007]. Recent studies have revealed metabolomic differences and potential biomarkers in AH of eye diseases, such as glaucoma [Myer et al., 2020], high myopia [Ji et al., 2017], and age-related macular degeneration [Han et al., 2020]. Nevertheless, the metabolomic landscape of AH and potential biomarkers in pediatric cataract are still obscure.

This study aimed to investigate the metabolite profile of AH samples obtained from patients with pediatric cataracts by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based metabolomics, which may help improve the understanding of pathophysiological metabolic characteristics and etiologies and find new intervention targets.