Ascorbic acid metabolites are involved in intraocular pressure control in the general population.
Hysi, Pirro G
Khawaja, Anthony P
Foster, Paul J
Benet, Leslie Z
Spector, Tim D
Hammond, Chris J
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Hysi, P. G., Khawaja, A. P., Menni, C., Tamraz, B., Wareham, N., Khaw, K., Foster, P. J., et al. (2019). Ascorbic acid metabolites are involved in intraocular pressure control in the general population.. Redox Biol, 20 349-353. https://doi.org/10.1016/j.redox.2018.10.004
Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to further explore the strength and directionality of effect of the metabolites on IOP. We show that O-methylascorbate, a circulating Vitamin C metabolite, has a significant IOP-lowering effect, consistent with previous knowledge of the anti-hypertensive and anti-oxidative role of ascorbate compounds. These results enhance understanding of IOP control and may potentially benefit future IOP treatment and reduce vision loss from glaucoma.
Humans, Glaucoma, Ascorbic Acid, Intraocular Pressure, Adult, Aged, Middle Aged, Female, Male, Metabolomics, Metabolome, Public Health Surveillance
Acknowledgements & Author Contributions EPIC-Norfolk infrastructure and core functions are supported by grants from the Medical Research Council (G1000143) and Cancer Research UK (C864/A14136). The clinic for the third health examination was funded by Research into Ageing (262). Genotyping was funded by the Medical Research Council (MC_PC_13048). We thank all staff from the MRC Epidemiology laboratory team for the preparation and quality control of DNA samples. Mr Khawaja is supported by a Moorfields Eye Charity fellowship. Professor Foster has received additional support from the Richard Desmond Charitable Trust (via Fight for Sight) and the Department for Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital and the UCL Institute of Ophthalmology for a specialist Biomedical Research Centre for Ophthalmology. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, the National Institute for Health Research (NIHR) – funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. CH and PH acknowledge the support from the TFC Frost Charitable Trust.
Medical Research Council (MC_UU_12015/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
External DOI: https://doi.org/10.1016/j.redox.2018.10.004
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286829
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/