Abstract

To investigate aqueous metabolic profiles in Vogt-Koyanagi-Harada (VKH) and Behcet’s disease (BD), we applied ultra-high-performance liquid chromatography equipped with quadrupole time-of flight mass spectrometry in aqueous humor samples collected from these patients and controls. Metabolite levels in these three groups were analyzed by univariate logistic regression. The differential metabolites were subjected to subsequent pathway analysis by MetaboAnalyst. The results showed that both partial-least squares discrimination analysis and hierarchical clustering analysis showed specific aqueous metabolite profiles when comparing VKH, BD, and controls. There were 28 differential metabolites in VKH compared to controls and 29 differential metabolites in BD compared to controls. Amino acids and fatty acids were the two most abundant categories of differential metabolites. Furthermore, pathway enrichment analysis identified several perturbed pathways, including pantothenate and CoA biosynthesis when comparing VKH with the control group, and D-arginine and D-ornithine metabolism and phenylalanine metabolism when comparing BD with the control group. Aminoacyl-tRNA biosynthesis was altered in both VKH and BD when compared to controls. Our findings suggest that amino acids metabolism as well as two fatty acids, palmitic acid and oleic acid, may be involved in the pathogenesis of BD and VKH.

Highlights

  • Uveitis known as intraocular inflammation is one of the leading causes of visual impairment and blindness in the world [1, 2]

  • We found that aqueous humor from VKH and Behcet’s disease (BD) patients showed distinct metabolic profiles compared to senile cataract controls

  • 28 and 29 metabolites were differentially expressed for VKH vs. control and BD vs. control, respectively

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Summary

Introduction

Uveitis known as intraocular inflammation is one of the leading causes of visual impairment and blindness in the world [1, 2]. Vogt-Koyanagi-Harada (VKH) disease and Behcet’s disease (BD) are two of the most commonly seen uveitis entities in China [3, 4]. The incidence rate of uveitis in China is 111.3 persons per 100,000 person-years [5] and a frequency of 12.7% and 8.7% has been reported for VKH and BD in Chinese uveitis patients, respectively [4]. VKH disease is a multisystemic autoimmune disease characterized by recurrent bilateral granulomatous panuveitis accompanied. Metabolomic Analysis of Vogt-Koyanagi-Harada and Behcet’s Disease with systemic involvements including poliosis, alopecia, vitiligo, central nervous system, and auditory abnormalities [6]. BD is recognized as an autoinflammatory disorder accompanied with recurrent uveitis, oral aphthae, genital ulcers, and typical skin lesions [7]. The exact pathogenesis of both VKH disease and BD remains unclear and omics analysis may advance the understanding of these diseases

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