Ascorbic acid metabolites are involved in intraocular pressure control in the general population
Pirro G. Hysi,
Anthony P. Khawaja,
Cristina Menni,
Bani Tamraz,
Nick Wareham,
Kay-Tee Khaw,
Paul J. Foster,
Leslie Z. Benet,
Tim D. Spector,
Chris J. Hammond
Affiliations
Pirro G. Hysi
Section of Academic Ophthalmology, Faculty of Life Sciences and Medicine, Kings' College London, UK; King’s College London Department of Twin Research and Genetic Epidemiology, London, UK; Corresponding author at: Section of Academic Ophthalmology, Faculty of Life Sciences and Medicine, Kings' College London, UK.
Anthony P. Khawaja
Department of Public Health & Primary Care, University of Cambridge, UK; NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and University College London, UK
Cristina Menni
King’s College London Department of Twin Research and Genetic Epidemiology, London, UK
Bani Tamraz
University of California, San Francisco, School of Pharmacy, San Francisco, CA, USA
Nick Wareham
Department of Public Health & Primary Care, University of Cambridge, UK
Kay-Tee Khaw
Department of Public Health & Primary Care, University of Cambridge, UK
Paul J. Foster
NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and University College London, UK
Leslie Z. Benet
University of California, San Francisco, School of Pharmacy, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA
Tim D. Spector
King’s College London Department of Twin Research and Genetic Epidemiology, London, UK
Chris J. Hammond
Section of Academic Ophthalmology, Faculty of Life Sciences and Medicine, Kings' College London, UK; King’s College London Department of Twin Research and Genetic Epidemiology, London, UK
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. Keywords: Ascorbate metabolism, Intraocular pressure, Multi-omics
