Abstract
To characterize metabolites and metabolic pathways altered in intermediate and neovascular age-related macular degeneration (IAMD and NVAMD), high resolution untargeted metabolomics was performed via liquid chromatography-mass spectrometry on plasma samples obtained from 91 IAMD patients, 100 NVAMD patients, and 195 controls. Plasma metabolite levels were compared between: AMD patients and controls, IAMD patients and controls, and NVAMD and IAMD patients. Partial least-squares discriminant analysis and linear regression were used to identify discriminatory metabolites. Pathway analysis was performed to determine metabolic pathways altered in AMD. Among the comparisons, we identified 435 unique discriminatory metabolic features. Using computational methods and tandem mass spectrometry, we identified 11 metabolic features whose molecular identities had been previously verified and confirmed the molecular identities of three additional discriminatory features. Included among the discriminatory metabolites were acylcarnitines, phospholipids, amino acids, and steroid metabolites. Pathway analysis revealed that lipid, amino acid, and vitamin metabolism pathways were altered in NVAMD, IAMD, or AMD in general, including the carnitine shuttle pathway which was significantly altered in all comparisons. Finally, few discriminatory features were identified between IAMD patients and controls, suggesting that plasma metabolic profiles of IAMD patients are more similar to controls than to NVAMD patients.
Highlights
Age-related macular degeneration (AMD) is a significant health burden in the aging population
Age was significantly different in all comparisons, with all AMD patient groups older than controls, and neovascular AMD (NVAMD) patients older than intermediate AMD (IAMD) patients
There were no significant associations between AMD, NVAMD, or IAMD and sex, body mass index (BMI), smoking status, diabetes, hypertension, or hyperlipidemia
Summary
Age-related macular degeneration (AMD) is a significant health burden in the aging population. It is the leading cause of vision loss in individuals over age 60, affecting an estimated 150 million people worldwide, and this number is expected to reach 288 million by the year 2040 [1]. The stages of AMD are broadly categorized as early, intermediate, and advanced. Vision loss often occurs in advanced AMD which includes two types: geographic atrophy, in which retinal cells gradually degenerate, and neovascular AMD (NVAMD), characterized by the formation and proliferation of new choroidal blood vessels. The aberrant new vessels in NVAMD cause exudation and macular edema, resulting in retinal damage and severe vision loss. The majority of AMD-related vision loss is caused by NVAMD [3,4]
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