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Metabolomic characteristics of aqueous humor in young myopia patients without fundus complications

Eye (2025)Cite this article

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Abstract

Background

To explore the potential mechanisms of myopia by detecting metabolites in the aqueous humour (AH) of young patients with myopia without fundus complications.

Methods

Randomised controlled trials (RCTs). A total of 65 AH samples (65 eyes) were collected in Weifang Eye Hospital. Untargeted metabolomics was conducted via liquid chromatography‒tandem mass spectrometry (LC‒MS/MS). Receiver operating characteristic (ROC) curves were generated.

Results

Patients were divided into three groups according to axial length (AL). There were 21 patients (21 eyes) in the moderate-myopia (MM) group (24.00 mm < AL ≤ 26.00 mm), 24 patients (24 eyes) in the high-myopia (HM) group (26.00 mm < AL ≤ 28.00 mm), and 20 patients (20 eyes) in the ultrahigh-myopia (UHM) group (AL > 28.00 mm). A total of 2203 metabolites were detected in the AH samples, and there were 62 shared differentially abundant metabolites among the three groups. KEGG pathways among the three groups included sphingolipid metabolism, lipid and atherosclerosis, and the pentose phosphate pathway (PPP). The key metabolites DL-glutamine, phytosphingosine, D-erythrose 4-phosphate, and pyridoxine phosphate exhibited the strongest correlations with AL (all P values were <0.0001). In the ROC analysis, DL-glutamine, phytosphingosine, and D-erythrose 4-phosphate were good biomarkers for MM. Pyridoxine phosphate was a potential biomarker for UHM.

Conclusions

Abnormal sphingolipid metabolism was closely related to myopia. Changes in phytosphingosine levels in the AH among various AL groups may serve as early warning signs of retinal changes. These metabolic pathways and metabolites could serve as intervention targets for myopia management in the future.

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Fig. 1: Overall experimental process.
Fig. 2: Metabolomic profiling and differential abundance analysis of aqueous humour (AH) in myopic patients.
Fig. 3: Cluster and functional enrichment analysis of differentially abundant metabolites (DAMs) among groups.
Fig. 4: Correlation analysis of key metabolites and axial length (AL).

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Data availability

The data generated and analysed during the current study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China [grant no. 82271114]; the Natural Science Foundation of Zhejiang Province, China [grant no. LZ22H120001 and ZCLTGD24H1201]; Science and Technology Development Plan Project of Weifang, Shandong Province, China [grant no. 2023YX070 and 2025ZJ1121].

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Author notes

  1. These authors contributed equally: Mengjun Fu, Xiaobo Zhang.

Authors and Affiliations

  1. State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Mengjun Fu, Xiaobo Zhang, Xiangyuan Song, Yijie Xu & Zai-Long Chi

  2. Weifang Eye Institute, National key clinical specialty, Weifang Eye Hospital, Zhengda Guangming Eye Group, Weifang, China

    Mengjun Fu, Jingjing Zhao, Jiahao Wang, Yongchao Wang, Kunning Wang & Haorun Zhang

  3. National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Xiaobo Zhang & Zai-Long Chi

  4. Department of Ophthalmology, Yinzhou People’s Hospital, Medical School of Ningbo University, Ningbo, China

    Qihu Tong

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Contributions

MF and XZ: conducted the experiments and wrote the manuscript. XS and YX: statistical analysis and figures. JZ, JW, YW, and KW: ICL preoperation and postoperation examinations and data collection. HZ and QT: ICL surgery and AH collection. Z-LC: designed the study and revised the manuscript.

Corresponding authors

Correspondence to Haorun Zhang or Zai-Long Chi.

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The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Weifang Eye Hospital (approval number: 2023-01-03) and was in compliance with the Declaration of Helsinki.

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Fu, M., Zhang, X., Song, X. et al. Metabolomic characteristics of aqueous humor in young myopia patients without fundus complications. Eye (2025). https://doi.org/10.1038/s41433-025-04168-4

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