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Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy

Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowerin...

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Autores principales: Tang, Yizhen, Pan, Yiqiong, Chen, Yuhong, Kong, Xiangmei, Chen, Junyi, Zhang, Hengli, Tang, Guangxian, Wu, Jihong, Sun, Xinghuai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080440/
https://www.ncbi.nlm.nih.gov/pubmed/33935712
http://dx.doi.org/10.3389/fphar.2021.621146
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author Tang, Yizhen
Pan, Yiqiong
Chen, Yuhong
Kong, Xiangmei
Chen, Junyi
Zhang, Hengli
Tang, Guangxian
Wu, Jihong
Sun, Xinghuai
author_facet Tang, Yizhen
Pan, Yiqiong
Chen, Yuhong
Kong, Xiangmei
Chen, Junyi
Zhang, Hengli
Tang, Guangxian
Wu, Jihong
Sun, Xinghuai
author_sort Tang, Yizhen
collection PubMed
description Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3′-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways.
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spelling pubmed-80804402021-04-29 Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy Tang, Yizhen Pan, Yiqiong Chen, Yuhong Kong, Xiangmei Chen, Junyi Zhang, Hengli Tang, Guangxian Wu, Jihong Sun, Xinghuai Front Pharmacol Pharmacology Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3′-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways. Frontiers Media S.A. 2021-04-14 /pmc/articles/PMC8080440/ /pubmed/33935712 http://dx.doi.org/10.3389/fphar.2021.621146 Text en Copyright © 2021 Tang, Pan, Chen, Kong, Chen, Zhang, Tang, Wu and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Tang, Yizhen
Pan, Yiqiong
Chen, Yuhong
Kong, Xiangmei
Chen, Junyi
Zhang, Hengli
Tang, Guangxian
Wu, Jihong
Sun, Xinghuai
Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
title Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
title_full Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
title_fullStr Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
title_full_unstemmed Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
title_short Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
title_sort metabolomic profiling of aqueous humor and plasma in primary open angle glaucoma patients points towards novel diagnostic and therapeutic strategy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080440/
https://www.ncbi.nlm.nih.gov/pubmed/33935712
http://dx.doi.org/10.3389/fphar.2021.621146
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