Metabolite Changes in the Aqueous Humor of Patients With Retinal Vein Occlusion Macular Edema: A Metabolomics Analysis.

Xiaojing Xiong,Zhu Chen,Xu Chen,Qingwei Chen,Jiaxin Pu,Zixi Zhou,Yazhu Yang,Huafeng Ma,Zheng Zheng,Minming Zheng

doi:10.3389/fcell.2021.762500

Abstract

Macular edema (ME) is the main cause of visual impairment in patients with retinal vein occlusion (RVO). The degree of ME affects the prognosis of RVO patients, while it lacks objective laboratory biomarkers. We aimed to compare aqueous humor samples from 28 patients with retinal vein occlusion macular edema (RVO-ME) to 27 age- and sex-matched controls by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry, so as to identify the key biomarkers and to increase the understanding of the mechanism of RVO-ME at the molecular level. Through univariate and multivariate statistical analyses, we identified 60 metabolites between RVO-ME patients and controls and 40 differential metabolites in mild RVO-ME [300 μm ≤ central retinal thickness (CRT) < 400 μm] patients compared with severe RVO-ME (CRT ≥ 400 μm). Pathway enrichment analysis showed that valine, leucine, and isoleucine biosynthesis; ascorbate and aldarate metabolism; and pantothenate and coenzyme A biosynthesis were significantly altered in RVO-ME in comparison with controls. Compared with mild RVO-ME, degradation and biosynthesis of valine, leucine, and isoleucine; histidine metabolism; beta-alanine metabolism; and pantothenate and coenzyme A biosynthesis were significantly changed in severe RVO-ME. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that adenosine, threonic acid, pyruvic acid, and pyro-L-glutaminyl-l-glutamine could differentiate RVO-ME from controls with an area under the curve (AUC) of >0.813. Urocanic acid, diethanolamine, 8-butanoylneosolaniol, niacinamide, paraldehyde, phytosphingosine, 4-aminobutyraldehyde, dihydrolipoate, and 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide had an AUC of >0.848 for distinguishing mild RVO-ME from severe RVO-ME. Our study expanded the understanding of metabolomic changes in RVO-ME, which could help us to have a good understanding of the pathogenesis of RVO-ME.

Highlights

Retinal vein occlusion (RVO) is the major cause of vision loss by retinal vascular diseases
We explored the metabolomic changes in AH of patients with retinal vein occlusion (RVO)-Macular edema (ME) disease
To the best of our knowledge, this is the first time that UHPC-Q-TOF/MS was used to analyze the discrepancy of AH metabolomics in retinal vein occlusion macular edema (RVO-ME) versus controls and mild RVO-ME (mRVO-ME) versus severe RVO-ME (sRVO-ME)

Summary

Introduction

Retinal vein occlusion (RVO) is the major cause of vision loss by retinal vascular diseases. Classified by the location of obstruction, RVO can be differentiated into central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Known risk factors for RVO include hypertension, atherosclerosis, hyperlipidemia, diabetes, thrombosis, and other inflammatory and myeloproliferative diseases (Petr, 2014; Balaratnasingam et al, 2016). Clinical presentations of RVO include retinal hemorrhage, tortuous retinal veins, optic nerve swelling, and macular edema (ME) (Querques et al, 2013). The most common cause of vision loss in RVO is ME. The diagnosis of retinal vein occlusion macular edema (RVO-ME) was undoubted, the initial pathogenesis and following pathophysiology of RVO-ME remained controversial

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