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Deeba Husain, Ines Laines, Ana Sofia Martins, Daniela Duarte, Antonio Barros, Rufino Martins Silva, Ana Gil, Joan W Miller; Biofluids NMR metabolomics in Age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3710.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is multifactorial, combining phenotypic, environmental, and genetic risk factors. Likely due to this complexity, attempts to identify valid applicable biomarkers for AMD have been unsuccessful. The metabolome (typically comprising molecules <1 kDa) is downstream of the genome, transcriptome and is simultaneously affected by a wide range of environmental and lifestyle exposures. We performed a prospective, cross-sectional study aimed to evaluate the impact of AMD on biofluids metabolic profile.
We recruited subjects with confirmed diagnosis of AMD and a control group without any vitreoretinal disease, after Mass Eye and Ear institutional review board approval. All participants underwent a dilated ophthalmological exam, seven field fundus photographs, autofluorescence, and Spectral Domain ocular coherence tomography 20x20 degree including enhanced depth imaging protocol. We obtained medical history and lifestyle profiling (diet and exercise). Fasting blood and urine samples were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy (500MHz), through 1D spectra (plasma: standard, relaxation-edited and diffusion-edited; urine: standard only) and 2D spectra (on selected samples, to aid peak assignment). Multivariate statistical analysis involved Principal Component Analysis (PCA) and Partial Least Squares and Discriminant Analysis (PLS-DA), followed by Monte Carlo Cross Validation and Receiver Operating Characteristic curves. Metabolite variations were quantified through signal integration and significance assessment.
We included 51 AMD patients (68.6% female) and 9 controls (66.7% female), mean aged 73.5 ± 7.9 and 65.2 ± 7.3, respectively. PLS-DA of plasma spectra suggested differences in lipid levels and amino acids in AMD patients as compared to controls. We found increased levels of unsaturated lipids, glucose and branched-chain amino acids - isoleucine, leucine, valine. These differences were more pronounced in patients with late AMD. The excretory metabolome seemed less sensitive to AMD, compared to plasma.
Our data suggests that AMD patients have altered metabolomic profiles compared to controls. Biofluid metabolomics offers the potential to identify biomarkers for AMD. Based on this preliminary data, we are carrying out a larger study to further explore metabolomics in patients with AMD across different stages of disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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