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Metabolomic profile of diabetic retinopathy: a GC-TOFMS-based approach using vitreous and aqueous humor

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Abstract

Aim

To identify the potential metabolite markers in diabetic retinopathy (DR) by using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS).

Methods

GC-TOFMS spectra were acquired from vitreous and aqueous humor (AH) samples of patients with DR and non-diabetic participants. Comparative analysis was used to elucidate the distinct metabolites of DR. Metabolic pathway was employed to explicate the metabolic reprogramming pathways involved in DR. Logistic regression and receiver-operating characteristic analyses were carried out to select and validate the biomarker metabolites and establish a therapeutic model.

Results

Comparative analysis showed a clear separation between disease and control groups. Eight differentiating metabolites from AH and 15 differentiating metabolites from vitreous were highlighted. Out of these 23 metabolites, 11 novel metabolites have not been detected previously. Pathway analysis identified nine pathways (three in AH and six in vitreous) as the major disturbed pathways associated with DR. The abnormal of gluconeogenesis, ascorbate–aldarate metabolism, valine–leucine–isoleucine biosynthesis, and arginine–proline metabolism might weigh the most in the development of DR. The AUC of the logistic regression model established by d-2,3-Dihydroxypropanoic acid, isocitric acid, fructose 6-phosphate, and l-Lactic acid in AH was 0.965. The AUC established by pyroglutamic acid and pyruvic acid in vitreous was 0.951.

Conclusions

These findings have expanded our understanding of identified metabolites and revealed for the first time some novel metabolites in DR. These results may provide useful information to explore the mechanism and may eventually allow the development of metabolic biomarkers for prognosis and novel therapeutic strategies for the management of DR.

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Acknowledgements

We acknowledge Dr Xun Xu (MD) from our department for providing medical writing assistant.

Funding

Funding

This work was supported in part by grants from National Key R&D Program of China (No. 2016YFC0904800) and National Natural Science Foundation of China (No. 81870666).

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Author notes

  1. Haiyan Wang and Junwei Fang have contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China

    Haiyan Wang, Fenge Chen, Qian Sun, Xiaoyin Xu & Kun Liu

  2. College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Junwei Fang & Shu-Hai Lin

  3. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China

    Shu-Hai Lin

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  1. Haiyan Wang
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  4. Qian Sun
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Correspondence to Shu-Hai Lin or Kun Liu.

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The study was prospectively approved by the Ethics Committee of Shanghai First People’s Hospital of Shanghai Jiaotong University, and research was conducted in accordance to the Declaration of Helsinki.

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Wang, H., Fang, J., Chen, F. et al. Metabolomic profile of diabetic retinopathy: a GC-TOFMS-based approach using vitreous and aqueous humor. Acta Diabetol 57, 41–51 (2020). https://doi.org/10.1007/s00592-019-01363-0

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