UPLC-MS/MS-based serum metabolomics analysis for comprehensive pathological myopia profiling

Xin Liu; Yue Wu; Yuying Liu; Wenzhe Qian; Liandi Huang; Yixiang Wu; Bilian Ke

doi:10.1016/j.exer.2024.110152

UPLC-MS/MS-based serum metabolomics analysis for comprehensive pathological myopia profiling

Exp Eye Res. 2024 Nov 25:110152. doi: 10.1016/j.exer.2024.110152. Online ahead of print.

Authors

Xin Liu¹, Yue Wu¹, Yuying Liu¹, Wenzhe Qian¹, Liandi Huang¹, Yixiang Wu¹, Bilian Ke²

Affiliations

¹ Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Fundus Disease, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.
² Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China; Department of Ophthalmology, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine No. 160 Pujian Road, Shanghai, 200127, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Fundus Disease, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China. Electronic address: kebilian@126.com.

PMID: 39603320
DOI: 10.1016/j.exer.2024.110152

Abstract

Pathological myopia (PM) is associated with ocular morbidities that cause blindness. PM often occurs in eyes with high myopia (HM) while they are distinctly different. Identifying the differences in metabolites and metabolic pathways between patients with PM and HM may provide information about the pathogenesis of PM, which is currently unknown. This study aimed to reveal the comprehensive metabolic alterations associated with PM. Thirty patients with PM, 27 with simple HM and 27 with low myopia (LM) were enrolled in this study. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was performed, and a Venn diagram was generated to explore the overlapping differential metabolites and enriched pathways between each set of two groups. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacity of each metabolite marker. A total of 134, 125 and 81 differential metabolites were identified in each comparison. Thirty-two differential metabolites were overlapped between the PM vs HM comparison and the PM vs LM comparison. Of these 32 metabolites, 16 were common to all three comparisons; among these metabolites, high levels of 4-hydroxy-l-glutamic acid and low levels of succinic semialdehyde and 2,3-dinor-8-iso prostaglandin F2α appeared to be risk factors for PM. The remaining 16 metabolites were shared only between the PM versus HM and PM versus LM comparisons, most of which are lipid molecules. Pathway analysis revealed that alanine, aspartate and glutamate metabolism was the key metabolic pathway altered in PM patients. Overall, significant differences in the metabolites and metabolic pathways were observed in patients with PM. The metabolic differences identified in this study included differential factors between PM and HM patients, addressing current gaps in PM research. These findings provide a novel perspective of the molecular mechanism of PM.

Keywords: UPLC‒MS/MS; glutamic acid; lipid metabolism; metabolomics; pathological myopia; prostaglandin; succinic acid.