Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema

Abstract Background Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarker...

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Main Authors: Dan Jiang, Congcong Yan, Lina Ge, Chun Yang, Ying Huang, Yau Kei Chan, Chonghua Chen, Wei Chen, Meng Zhou, Bing Lin
Format: Article
Language:English
Published: BMC 2023-04-01
Series:Eye and Vision
Subjects:
Online Access:https://doi.org/10.1186/s40662-023-00331-8
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author Dan Jiang
Congcong Yan
Lina Ge
Chun Yang
Ying Huang
Yau Kei Chan
Chonghua Chen
Wei Chen
Meng Zhou
Bing Lin
author_facet Dan Jiang
Congcong Yan
Lina Ge
Chun Yang
Ying Huang
Yau Kei Chan
Chonghua Chen
Wei Chen
Meng Zhou
Bing Lin
author_sort Dan Jiang
collection DOAJ
description Abstract Background Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME. Methods Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways. Results The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME. Conclusions Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.
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spelling doaj.art-dcc3f378c00a410f9b8e0a87dbc50b892023-04-03T05:16:47ZengBMCEye and Vision2326-02542023-04-0110111110.1186/s40662-023-00331-8Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edemaDan Jiang0Congcong Yan1Lina Ge2Chun Yang3Ying Huang4Yau Kei Chan5Chonghua Chen6Wei Chen7Meng Zhou8Bing Lin9National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityDepartment of Ophthalmology, LKS Faculty of Medicine, The University of Hong KongNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityAbstract Background Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME. Methods Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways. Results The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME. Conclusions Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.https://doi.org/10.1186/s40662-023-00331-8Macular edemaLiquid chromatography-mass spectrometryMetabolic biomarkersMetabolomics
spellingShingle Dan Jiang
Congcong Yan
Lina Ge
Chun Yang
Ying Huang
Yau Kei Chan
Chonghua Chen
Wei Chen
Meng Zhou
Bing Lin
Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema
Eye and Vision
Macular edema
Liquid chromatography-mass spectrometry
Metabolic biomarkers
Metabolomics
title Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema
title_full Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema
title_fullStr Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema
title_full_unstemmed Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema
title_short Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema
title_sort metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema
topic Macular edema
Liquid chromatography-mass spectrometry
Metabolic biomarkers
Metabolomics
url https://doi.org/10.1186/s40662-023-00331-8
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