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

doi:10.1016/j.redox.2018.10.004

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

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Abstract

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.

Original language	English
Pages (from-to)	349-353
Number of pages	5
Journal	Redox Biology
Volume	20
Early online date	13 Oct 2018
DOIs	https://doi.org/10.1016/j.redox.2018.10.004
Publication status	Published - Jan 2019

Keywords

Ascorbate metabolism
Intraocular pressure
Multi-omics

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10.1016/j.redox.2018.10.004

Ascorbic acid metabolites are_HYSI_Firstonline13October2018_GREEN AAM (CC BY-NC-ND)Accepted author manuscript, 1 MB

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title = "Ascorbic acid metabolites are involved in intraocular pressure control in the general population",

abstract = "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",

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year = "2019",

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doi = "10.1016/j.redox.2018.10.004",

language = "English",

volume = "20",

pages = "349--353",

journal = "Redox Biology",

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T1 - Ascorbic acid metabolites are involved in intraocular pressure control in the general population

AU - Hysi, Pirro G.

AU - Khawaja, Anthony P.

AU - Menni, Cristina

AU - Tamraz, Bani

AU - Wareham, Nick

AU - Khaw, Kay-Tee

AU - Foster, Paul J.

AU - Benet, Leslie Z.

AU - Spector, Tim D.

AU - Hammond, Chris J.

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Ascorbate metabolism

KW - Intraocular pressure

KW - Multi-omics

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U2 - 10.1016/j.redox.2018.10.004

DO - 10.1016/j.redox.2018.10.004

M3 - Article

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VL - 20

SP - 349

EP - 353

JO - Redox Biology

JF - Redox Biology

ER -

Ascorbic acid metabolites are involved in intraocular pressure control in the general population

Abstract

Keywords

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