Untargeted metabolomics for uncovering plasma biological markers of wet age-related macular degeneration

• Published in: Aging (Albany, NY.) Vol. 13; no. 10; pp. 13968 - 14000
• Main Authors: Deng, Yanhui, Shuai, Ping, Wang, Haixin, Zhang, Shanshan, Li, Jie, Du, Mingyan, Huang, Peirong, Qu, Chao, Huang, Lulin
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 31.05.2021
• Subjects: Apoptosis; Bacteria - metabolism; Biomarkers - blood; Cell Proliferation; Choroidal Neovascularization - metabolism; Epithelial Cells - metabolism; Genetic Predisposition to Disease; Humans; Macular Degeneration - blood; Macular Degeneration - genetics; Macular Degeneration - metabolism; Metabolome; Metabolomics; Molecular Sequence Annotation; Necrosis; Neovascularization, Physiologic; Polymorphism, Single Nucleotide - genetics; Principal Component Analysis; Research Paper; Retinal Pigment Epithelium - pathology; Signal Transduction; metabonomics; PCV; CNV; plasma; wAMD
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.203006

Wet age-related macular degeneration (wAMD) causes central vision loss and represents a major health problem in elderly people. Here we have used untargeted metabolomics using UHPLC-MS to profile plasma from 127 patients with wAMD (67 choroidal neovascularization (CNV) and 60 polypoidal choroidal vasculopathy (PCV)) and 50 controls. A total of 545 biochemicals were detected. Among them, 17 metabolites presented difference between patients with wAMD and controls. Most of them were oxidized lipids (N=6, 35.29%). Comparing to controls, 28 and 18 differential metabolites were identified in patients with CNV and PCV, respectively. Two metabolites, hyodeoxycholic acid and L-tryptophanamide, were differently distributed between PCV and CNV. We first investigated the genetic association with metabolites in wet AMD ( rs800292 and rs10490924). We identified six differential metabolites between the GG and AA genotypes of rs800292, five differential metabolites between the GG and AA genotypes of rs10490924, and four differential metabolites between the GG and GA genotypes of rs10490924. We selected four metabolites (cyclamic acid, hyodeoxycholic acid, L-tryptophanamide and O-phosphorylethanolamine) for experiments. Among them, cyclamic acid reduced the activity, inhibited the proliferation, increased the apoptosis and necrosis in human retinal pigment epithelial cells (HRPECs). L-tryptophanamide affected the proliferation, apoptosis and necrosis in HRPECs, and promoted the tube formation and migration in primary human retinal endothelial cells (HRECs). Hyodeoxycholic acid and O-phosphorylethanolamine inhibited the tube formation and migration in HRECs. The results suggested that differential metabolites have certain effects on wAMD pathogenesis-related HRPECs and HRECs.