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Sasha Woods, Michael Powner, Senthil Selvam, Kamron Khan, Robyn H Guymer, Jennifer Trombley, Catherine Egan, Martin Friedlander, Marcus Fruttiger; Human Serum Metabolomics Study in Macular Telangiectasia Type 2. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3154.
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© ARVO (1962-2015); The Authors (2016-present)
Macular telangiectasia (MacTel) type 2 is an uncommon bilateral eye disease causing central vision loss. Retinal alterations begin in a temporal paracentral area, eventually affecting a characteristic oval region around the foveal centre. A recent genome-wide association study (GWAS) identified 5 genetic susceptibility loci for MacTel, 4 of which are implicated in the glycine/serine metabolic pathway. Furthermore, MacTel patients were shown to have reduced glycine/serine levels in their serum. Here we present a global metabolomics analysis of MacTel patients and matched controls.
50 patients and 50 independent controls (matched for age, sex, ethnicity and diabetes status) were selected from a number of participating centres. Following overnight fasting, blood samples were collected into serum separator tubes and centrifuged (1200rpm, 10 minutes, 20°C) after 30 minutes. Serum aliquots of 200µl were shipped to Metabolon Inc. in dry ice, where non-targeted mass-spectrometry (MS) analysis was performed using ultrahigh-performance liquid chromatography-tandem MS. To identify biochemicals that differed significantly between patients and controls and to correct for the false discovery rate (FDR), the Benjamin-Hochberg procedure was used.
In total, 1256 metabolites were identified in this study. Principal component analysis (PCA) revealed poor separation of MacTel patients from controls, indicating that the global metabolic profiles of the two groups were similar. 47 metabolites showed differences with p-values <0.05 and a further 25 had p-values ≥0.05 and ≤0.10. Amongst these, glycine and serine had the highest significance levels and were reduced by about 20% in MacTel patients. Further amino acids were also significantly lower in MacTel patients compared to controls, whilst a number of lipids – particularly phosphatidylethanolamines – were significantly higher (by about 20%). Moreover, MacTel patients also show evidence of increased levels of oxidative stress, associated with changes in cysteine/methionine metabolism.
Our data further implicates systemic abnormalities beyond the retinal phenotype in MacTel type 2 and identifies potential new biomarkers for this disease.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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