Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Vitreous metabolomic signatures of pathological myopia with complications

Eye volume 37, pages 2987–2993 (2023)Cite this article

Subjects

Abstract

Background

Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications.

Methods

VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis.

Results

Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications.

Conclusions

Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Results of multivariate analysis of the metabolic profile of PM with complications and control.
Fig. 2: Analysis of altered metabolites, pathways and potential markers in the PM with complications and control groups.
Fig. 3: Receiver operating characteristic (ROC) curves for metabolites distinguishing control and PM with vitreous complications.
Fig. 4: Venn diagram for altered metabolites based on pairwise analyses.

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Grochowski ET, Pietrowska K, Kowalczyk T, Mariak Z, Kretowski A, Ciborowski M, et al. Omics in Myopia. J Clin Med. 2020;9:3464.

  2. Chen M, Wu A, Zhang L, Wang W, Chen X, Yu X, et al. The increasing prevalence of myopia and high myopia among high school students in Fenghua city, eastern China: A 15-year population-based survey. BMC Ophthalmol. 2018;18:159.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Du B, Jin N, Zhu X, Lu D, Jin C, Li Z, et al. A prospective study of serum metabolomic and lipidomic changes in myopic children and adolescents. Exp Eye Res. 2020;199:108182.

    Article  CAS  PubMed  Google Scholar 

  4. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology. 2016;123:1036–42.

    Article  PubMed  Google Scholar 

  5. Dai L, Yang W, Qin X, Li Y, Cao H, Zhou C, et al. Serum metabolomics profiling and potential biomarkers of myopia using LC-QTOF/MS. Exp Eye Res. 2019;186:107737.

    Article  CAS  PubMed  Google Scholar 

  6. Rudnicka AR, Kapetanakis VV, Wathern AK, Logan NS, Gilmartin B, Whincup PH, et al. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention. Br J Ophthalmol. 2016;100:882–90.

    Article  PubMed  Google Scholar 

  7. Ohno-Matsui K, Kawasaki R, Jonas JB, Cheung CM, Saw SM, Verhoeven VJ, et al. International photographic classification and grading system for myopic maculopathy. Am J Ophthalmol. 2015;159:877–83.e7.

    Article  PubMed  Google Scholar 

  8. Wei Q, Zhang T, Fan J, Jiang R, Chang Q, Hong J, et al. Pathological myopia-induced antioxidative proteins in the vitreous humor. Ann Transl Med. 2020;8:193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Walline JJ, Lindsley K, Vedula SS, Cotter SA, Mutti DO, Twelker JD. Interventions to slow progression of myopia in children. Cochrane Database Syst Rev. 2011;1:CD004916.

  10. Sacks D, Baxter B, Campbell BCV, Carpenter JS, Cognard C, Dippel D, et al. Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke. Int J Stroke. 2018;13:612–32.

    PubMed  Google Scholar 

  11. Kell DB, Brown M, Davey HM, Dunn WB, Spasic I, Oliver SG. Metabolic footprinting and systems biology: The medium is the message. Nat Rev Microbiol. 2005;3:557–65.

    Article  CAS  PubMed  Google Scholar 

  12. Ke C, Xu H, Chen Q, Zhong H, Pan CW. Serum metabolic signatures of high myopia among older Chinese adults. Eye (Lond). 2021;35:817–24.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang X, Wang X, Le S, Ojanen X, Cheng S. Effects of exercise and dietary interventions on serum metabolites in men with insomnia symptoms: A 6-month randomized controlled trial. Sports Med Health Sci. 2020;2:95–101.

  14. Kameda M, Teruya T, Yanagida M, Kondoh H. Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility. Proc Natl Acad Sci USA. 2020;117:9483–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wei R, Wang J, Su M, Jia E, Chen S, Chen T, et al. Missing value imputation approach for mass spectrometry-based metabolomics data. Sci Rep. 2018;8:663.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Barbas-Bernardos C, Armitage EG, García A, Mérida S, Navea A, Bosch-Morell F, et al. Looking into aqueous humor through metabolomics spectacles - exploring its metabolic characteristics in relation to myopia. J Pharm Biomed Anal. 2016;127:18–25.

    Article  CAS  PubMed  Google Scholar 

  17. Preidis GA, Keaton MA, Campeau PM, Bessard BC, Conner ME, Hotez PJ. The undernourished neonatal mouse metabolome reveals evidence of liver and biliary dysfunction, inflammation, and oxidative stress. J Nutr. 2014;144:273–81.

    Article  CAS  PubMed  Google Scholar 

  18. Quifer-Rada P, Chiva-Blanch G, Jáuregui O, Estruch R, Lamuela-Raventós RM. A discovery-driven approach to elucidate urinary metabolome changes after a regular and moderate consumption of beer and nonalcoholic beer in subjects at high cardiovascular risk. Mol Nutr Food Res. 2017;61. https://doi.org/10.1002/mnfr.201600980.

  19. Romagnoli G, Verhoeven MD, Mans R, Fleury Rey Y, Bel-Rhlid R, van den Broek M, et al. An alternative, arginase-independent pathway for arginine metabolism in Kluyveromyces lactis involves guanidinobutyrase as a key enzyme. Mol Microbiol. 2014;93:369–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jiang Q, Wang C, Xue C, Xue L, Wang M, Li C, et al. Changes in the levels of l-carnitine, acetyl-l-carnitine and propionyl-l-carnitine are involved in perfluorooctanoic acid induced developmental cardiotoxicity in chicken embryo. Environ Toxicol Pharm. 2016;48:116–24.

    Article  CAS  Google Scholar 

  21. Pessotto P, Valeri P, Arrigoni-Martelli E. The presence of L-carnitine in ocular tissues of the rabbit. J Ocul Pharm. 1994;10:643–51.

    Article  CAS  Google Scholar 

  22. Parvanova A, Trillini M, Podestà MA, Iliev IP, Aparicio C, Perna A, et al. Blood pressure and metabolic effects of Acetyl-l-Carnitine in Type 2 diabetes: DIABASI randomized controlled trial. J Endocr Soc. 2018;2:420–36.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ji Y, Rao J, Rong X, Lou S, Zheng Z, Lu Y. Metabolic characterization of human aqueous humor in relation to high myopia. Exp Eye Res. 2017;159:147–55.

    Article  CAS  PubMed  Google Scholar 

  24. Savitz J. The kynurenine pathway: A finger in every pie. Mol Psychiatry. 2020;25:131–47.

    Article  PubMed  Google Scholar 

  25. Platten M, Nollen EAA, Röhrig UF, Fallarino F, Opitz CA. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Disco. 2019;18:379–401.

    Article  CAS  Google Scholar 

  26. Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health. Science 2017;357:eaaf9794.

  27. Comai S, Bertazzo A, Brughera M, Crotti S. Tryptophan in health and disease. Adv Clin Chem. 2020;95:165–218.

    Article  CAS  PubMed  Google Scholar 

  28. George A, Schmid KL, Pow DV. Retinal serotonin, eye growth and myopia development in chick. Exp Eye Res. 2005;81:616–25.

    Article  CAS  PubMed  Google Scholar 

  29. Best SA, Midgley JM, Huang W, Watson DG. The determination of 5-hydroxytryptamine, related indolealkylamines and 5-hydroxyindoleacetic acid in the bovine eye by gas chromatography-negative ion chemical ionization mass spectrometry. J Pharm Biomed Anal. 1993;11:323–33.

    Article  CAS  PubMed  Google Scholar 

  30. Mármol F, Sanchez J, Martínez-Pinteño A. Effects of uric acid on oxidative and nitrosative stress and other related parameters in SH-SY5Y human neuroblastoma cells. Prostaglandins Leukot Ess Fat Acids. 2021;165:102237.

    Article  Google Scholar 

  31. de Lau LM, Koudstaal PJ, Hofman A, Breteler MM. Serum uric acid levels and the risk of Parkinson disease. Ann Neurol. 2005;58:797–800.

    Article  PubMed  Google Scholar 

  32. Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, et al. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA. 1998;95:675–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Packer M. Uric Acid is a biomarker of oxidative stress in the failing heart: Lessons learned from trials with Allopurinol and SGLT2 inhibitors. J Card Fail. 2020;26:977–84.

    Article  PubMed  Google Scholar 

  34. Li S, Shao M, Li D, Tang B, Cao W, Sun X. Association of serum uric acid levels with primary open-angle glaucoma: A 5-year case-control study. Acta Ophthalmol. 2019;97:e356–e63.

    Article  CAS  PubMed  Google Scholar 

  35. Francisco BM, Salvador M, Amparo N. Oxidative stress in myopia. Oxid Med Cell Longev. 2015;2015:750637.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by the Zhejiang Provincial Natural Science Foundation of China (LY20H120004).

Author information

Author notes

  1. These authors contributed equally: Yongping Tang, Xiaobo Zhang.

Authors and Affiliations

  1. National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China

    Yong-Ping Tang, Xiao-Bo Zhang, Zhi-Xiang Hu, Ke Lin, Zhong Lin, Tian-Yu Chen, Rong-Han Wu & Zai-Long Chi

  2. State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China

    Xiao-Bo Zhang & Zai-Long Chi

Authors
  1. Yong-Ping Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-Xiang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ke Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhong Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tian-Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rong-Han Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zai-Long Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZLC and RHW designed the study. ZXH, KL, ZL, and TYC recruited the patients and collected the samples. YPT and XBZ performed the metabolomics analysis and analysed the data. YPT, XBZ, RHW, and ZLC wrote the manuscript. All authors provided final approval of the version to be published.

Corresponding authors

Correspondence to Rong-Han Wu or Zai-Long Chi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, YP., Zhang, XB., Hu, ZX. et al. Vitreous metabolomic signatures of pathological myopia with complications. Eye 37, 2987–2993 (2023). https://doi.org/10.1038/s41433-023-02457-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41433-023-02457-4

Search

Advanced search

Quick links