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Ines Lains, Rachel S. Kelly, Jessica Lasky-Su, Rufino Silva, Joaquim N Murta, John B Miller, Ivana K Kim, Demetrios G. Vavvas, Joan W Miller, Deeba Husain; Plasma Mass-spectrometry Metabolomics in Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3764.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related Macular Degeneration (AMD) is multifactorial, combining environmental and genetic risk factors. Likely due to this complexity, reliable AMD biomarkers in biofluids are still lacking. The metabolome, the global profile of all the small molecules (<1 kDa) comprising a biological system, is the downstream product of the cumulative effects of the genome and environmental exposures. This study performed mass-spectrometry (MS) based metabolomic profiling of plasma to explore the metabolome of AMD and identify potential metabolic AMD biomarkers.
Prospective, cross-sectional study, including subjects with a diagnosis of AMD and a control group (> 50 years) without any vitreoretinal disease. All participants were imaged with color fundus photographs, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study (AREDS) classification scheme. Fasting blood samples were collected and analyzed by Metabolon, Inc (Durham, NC), using ultra-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon’s hardware and software were used for peak-identification and quality control. Metabolite variations were quantified through signal integration and significance assessment (ANOVA tests).
We included 90 patients with AMD (30 early, 30 intermediate, 30 late AMD; 64.4% female) and 30 controls (60.0% female), mean age 68.1 ± 10.2 and 71.3 ± 7.5 years, respectively. Using UPLC-MS, 878 biochemicals were identified. The comparison between all AMD patients and controls revealed statistically significant differences in fatty acid metabolites (in particular those related to acyl carnitine, p≤ 0.04), cell membrane (namely phosphatidylcholine, phosphatidyl-ethanolamine and phosphatidyl-inositol, p≤ 0.04) and vitamin A metabolites (p=0.01). Compared to controls, subjects with more severe AMD demonstrated greater differences in plasma metabolites.
Our data suggests that patients with AMD have altered plasma metabolomic profiles compared to controls. As the disease severity increases, an increasing number of changes are evident. These findings support the development of plasma-based metabolomics biomarkers of AMD, which will be the focus of subsequent analyses.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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