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Christopher J. Hammond, Pirro G. Hysi, Nicole Soranzo, Christian Gieger, Timothy D. Spector; Metabolomic Profiling of Age-Related Cataract. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2741.
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The study of metabolomics, profiling of small molecules in small samples, is an emerging approach for biological research. Metabolic traits as functional intermediates may act as biomarkers and help identify functional pathways in some cases better than other existing methodologies because they are a measurable direct product of genes and environmental factors. Genetic associations have identified risk loci for many complex diseases, which in the case of cataract are still eluding identification. The aim of the study was to explore the relationship between age-related cataract and serum metabolites, given the known associations of cataract with metabolic dysfunctions.
1052 population-representative volunteers, mean age 63 years (range 50-81) from the TwinsUK Adult Twin Registry underwent non-targeted metabolomic analysis of plasma samples, using gas- and liquid-chromatography in combination with mass spectrometry (Metabolon Inc, Durham, NC), to quantitatively measure c.250 metabolites in plasma samples. The participants also had quantitative assessment of cataract using digital Scheimpflug lens images for nuclear cataract, and retroillumination images for cortical cataract. Analysis was assessed in linear regression models that included age of the subjects.
The strongest association for cortical cataract was 3-methoxytyrosine (p<0.001). The EPHA2 receptor tyrosine kinase gene has previously been reported as associated with age-related cortical cataract; animal models fed low protein high tyrosine diets also develop cataract. The strongest associations with nuclear cataract were laurate (p=0.003), 4-ethylphenyl sulphate (p=0.006) and malate (p=0.008). Malate dehydrogenase is inactivated by non-enzymic glycosylation (glycation) of structural proteins by glucose, which is inhibited by α-crystallin in the lens.
A metabolomic approach has suggested some candidate pathways which may be involved in development of age-related cataract, including further confirmation of tyrosine metabolism pathway in aetiology of cortical cataract. Further research is necessary to elucidate these pathways.
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