Urine Nuclear Magnetic Resonance (NMR) Metabolomics in Age-Related Macular Degeneration

Abstract

Biofluid biomarkers of age-related macular degeneration (AMD) are still lacking, and their identification is challenging. Metabolomics is well-suited to address this need, and urine is a valuable accessible biofluid. This study aimed to characterize the urinary metabolomic signatures of patients with different stages of AMD and a control group (>50 years). It was a prospective, cross-sectional study, where subjects from two cohorts were included: 305 from Coimbra, Portugal (AMD patients n = 252; controls n = 53) and 194 from Boston, United States (AMD patients n = 147; controls n = 47). For all participants, we obtained color fundus photographs (for AMD staging) and fasting urine samples, which were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy. Our results revealed that in both cohorts, urinary metabolomic profiles differed mostly between controls and late AMD patients, but important differences were also found between controls and subjects with early AMD. Analysis of the metabolites responsible for these separations revealed that, even though distinct features were observed for each cohort, AMD was in general associated with depletion of excreted citrate and selected amino acids at some stage of the disease, suggesting enhanced energy requirements. In conclusion, NMR metabolomics enabled the identification of urinary signals of AMD and its severity stages, which might represent potential metabolomic biomarkers of the disease.

Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration

“…A recent metabolomics study in urine samples also showed depleted citrate and amino acid levels in AMD, which was suggested to reflect an enhancement in energy requirement in the disease. 47 Decreased amino acid levels (valine, isoleucine, leucine) have also been reported in dementia. 41 Valine, isoleucine, leucine, and phenylalanine are essential amino acids, and circulating levels are determined largely by dietary intake.…”

Metabolomics in Age-Related Macular Degeneration: A Systematic Review

“…Three of the studies were by the same author on the same cohort, but there were differences in sample size, biological samples, test platform, and research grouping, so all of them were included in this review. [25][26][27] A total of four types of sampled tissues were involved in the study, including serum (n = 3), 4,10,28 plasma (n = 7), 25,27,[29][30][31][32][33] urine (n = 1), 26 aqueous humor (n = 1), and both serum and plasma (n = 1). 34,35 With regard to the analytical platforms used for metabolite detection, 10 studies used MS, and the other three used the NMR platform.…”

“…34,35 With regard to the analytical platforms used for metabolite detection, 10 studies used MS, and the other three used the NMR platform. 27,26,34 The sample sizes ranged from 40 to 6533 individuals. The study with the largest sample size came from a recent study based on five cohorts from Europe.…”

Metabolomic analysis in ophthalmology

“…Significant changes were found in N-acetyl-L-alanine, L-tyrosine, L-phenylalanine, L-methionine, and L-arginine, which leads to the conclusion that AMD may be also related to disorders in amino acid metabolism 72 . 1 H NMR spectroscopy study on urinary metabolomic signatures of patients with different stages of AMD and a control group reported depletion of some amino acids and citrate in adult AMD patients vs controls 71 . Serum GC-TOF-MS metabolome study on 446 patients with macular neovascularization (AMD, polypoidal choroidal vasculopathy, PCV, and pathological myopia, PM) and 138 cataract adults as controls, identified significant differences in 33 metabolites in the patients with macular neovascularization.…”

“…The dysregulation of purine, taurine and hypotaurine metabolism may be related to deregulation of cellular energy metabolism, disturbed antioxidant defense and neuroprotection. Glutamate and glutamine changes between AMD patients and controls as well as across AMD severity stages are possibly associated with disturbances in neurotransmitter supply, important for retina and visual pathway 70,71 . GC-MS/MS study on plasma metabolome profile of AMD patients and controls also reported disturbed amino acid metabolism in AMD patients.…”