PURPOSE: Primary congenital glaucoma (PCG) is an autosomal recessive eye disorder, accounting for 0.01%-0.04% of blindness around the world. Unfortunately, the molecular characteristics concerning the pathogenic mechanisms of the disease remain poorly understood. METHODS: Here, for the first time, we employed gas chromatography coupled to time-of-flight mass spectrometry (GC/TOF MS) to reveal comprehensively the metabolic characteristics of PCG. RESULTS: First, 363 metabolites were detected in 50 aqueous humor (AH) samples from 30 patients with PCG, 10 patients with congenital cataracts (CCs), and 10 patients with aged-related cataracts (ARCs). Second, 290 metabolites in total were found in another 15 patients with PCG and 10 patients with primary open angle glaucoma (POAG). A further analysis suggested that patients with PCG had a significantly distinct metabolomics profile. Three amino acid-associated metabolites, including glycine, urea, and phenylalanine, were identified to be significantly different (p≤0.05) in relation to PCG. Meanwhile, three glaucoma-associated single nucleotide polymorphisms (SNPs), rs7114303, rs9364602, and rs2165241, were determined to be related to these three metabolites. The results here indicate that certain amino acid-associated metabolites and their metabolisms are key regulatory elements and metabolic pathways in the pathogenesis of PCG. CONCLUSIONS: Collectively, this work not only extended our understanding of the molecular characteristics of PCG, but also presented glycine as a potential biomarker for earlier diagnosis and may provide new therapeutic strategies for the disease.
Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
9.1.1 Congenital glaucoma, Buphthalmos (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
2.6.3 Compostion (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.7 Biochemistry (Part of: 3 Laboratory methods)