Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy

Abstract

PurposeTo differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy.MethodsTwo cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis.ResultsSmall changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD.ConclusionFor the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.

Clinical Metabolomics and Glaucoma

“…In ophthalmology, metabolomics has been used to study various eye diseases including glaucoma [10][11][12][13][14][15][16] , age-related macular degeneration [17][18][19] , diabetic retinopathy [20][21][22] , keratoconus [23] , refractive error [24,25] , retinal detachment [26] , uveitis [27,28] , dry eye [29,30] , and other ocular surface diseases [31] . Analyses have been performed on tear fluid [23,[29][30][31][32] , aqueous humor [24,25,33,34] , vitreous humor [20,26,27,35,36] , cornea [37][38][39] , conjunctiva [40] , and lens [41,42] samples.…”

“…However, a correlation with disease stage has been shown for diabetic retinopathy [21] , as well as age-related macular degeneration [18,19] . Similar studies have been conducted in cancer research, one of the largest areas of metabolomics research; preserved blood and urine samples have been used to metabotype progressive and/or relapsing patients.…”

Re: Laíns et al.: Human plasma metabolomics study across all stages of age-related macular degeneration identifies potential lipid biomarkers ( Ophthalmology . 2018;125:245-254)

“…However, suboptimal sensitivity can be a major impediment to clinical implementation, because clinicians can be reluctant to trust results from point-of-care testing, and/or the need for back up laboratory test confirmation continues. 2 We are aware of 3 diagnostic accuracy studies of the AdenoPlus point-of-care test. The study we cited in our editorial 3 found a sensitivity of 39.5% in a hospital eye emergency department, Sambursky et al 4 found a much higher sensitivity of 85% to 90% (depending on the reference standard used) in ophthalmology private practices and academic centers, whereas Holtz et al 5 found a sensitivity of 50% in acute eye care clinics.…”

“…The results of the AMD biomarker found in the blood were different when compared with this study's results. 2 Second, it was noted that this study enrolled 30 controls and 90 patients with AMD; however, did the authors calculate the sample size? In their previous studies, they enrolled a total of 396 patients to test the plasma metabolomic profile in patients with AMD by nuclear magnetic resonance spectroscopy.…”

Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration

“…Although certain TCA-related organic acids were analyzed in the samples from Osborn et al, 28 the putative metabolite identifications still need to be confirmed by LC/MS and authentic standard samples. 29 Our AH quantitative analysis of AMD fingerprints, with particular interest in glucose-related metabolites, presented both similarities and differences with previous articles. First, AH showed no significant increase in lactate concentrations, which is the preferable production of aerobic glycolysis in the retina.…”