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Comparisons of the protein expressions between high myopia and moderate myopia on the anterior corneal stroma in human

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Abstract

Purpose

To investigate the differentially expressed proteins (DEP) between high myopia and moderate myopia on the anterior corneal stroma.

Methods

Tandem mass tag (TMT) quantitative proteomics was utilized to reveal proteins. DEPs were screened by the multiple change of more than 1.2 times or less than 0.83 and the P value < 0.05. The DEPs were functional annotated by Gene Ontology (GO) terms. Proteins and protein interaction (PPI) networks were conducted with String online tool. Parallel reaction monitoring (PRM) data processing was used to verify the TMT proteomics results.

Results

There are 36 DEPs between high myopia and moderate myopia on the anterior corneal stroma, of which 11 proteins are upregulated, 25 proteins are downregulated. The GO analysis demonstrated keratinocyte migration and structural constituent of cytoskeleton that are significantly changed with most of the proteins decreased in high myopic corneas. Keratin 16 (KRT16) and erythrocyte membrane protein band 4.1-like protein 4B are the only two proteins involved in both functions. The PPI analysis showed keratin type II cytoskeletal 6A (KRT6A) and KRT16 that have strong connections. Immunoglobulin lambda variable 8–61(IGLV8-61) and nicotinamide phosphoribosyl transferase (NAMPT) have consistent results with the TMT.

Conclusions

The high myopic corneas have 36 DEPs compared to the moderate myopic corneas on the anterior corneal stroma. Keratinocyte migrations and structural constituent of cytoskeleton are weakened in high myopic corneas, which may partly account for the lower corneal biomechanics in high myopic eyes. The lower expressed KRT16 plays important roles in high myopic corneas.

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Abbreviations

BP:

Biological processes

CC:

Cellular components

DEP:

Differentially expressed proteins

GO:

Gene Ontology

KEGG:

The Kyoto Encyclopedia of Genes and Genomes analysis

KRT:

Keratin

MF:

Molecular function

PPI:

Protein-protein interactions

PRM:

Parallel reaction monitoring

SMILE:

Femtosecond laser small incision lenticule extraction

TMT:

Tandem mass tag

References

  1. Tedja MS, Haarman AEG, Meester-Smoor MA, Kaprio J, Mackey DA, Guggenheim JA, Hammond CJ, Verhoeven VJM, Klaver CCW (2019) Consortium C: IMI - myopia genetics report. Invest Ophthalmol Vis Sci 60(3):M89–M105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cai XB, Shen SR, Chen DF, Zhang Q, Jin ZB (2019) An overview of myopia genetics. Exp Eye Res 188:107778

    Article  CAS  PubMed  Google Scholar 

  3. Wojciechowski R, Cheng CY (2018) Involvement of multiple molecular pathways in the genetics of ocular refraction and myopia. Retina 38(1):91–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dyrlund TF, Poulsen ET, Scavenius C, Nikolajsen CL, Thogersen IB, Vorum H, Enghild J (2012) Human cornea proteomeidentification and quantitation of the proteins of the three main layers including epithelium, stroma, and endothelium. J Proteome Res 11(8):4231–4239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen J, Wu W, Wang Z, Zhai C, Deng B, Alzogool M, Wang Y (2021) Novel corneal protein biomarker candidates reveal iron metabolic disturbance in high myopia eyes. Front Cell Dev Biol 9:689917

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wu W, Dou R, Wang Y (2019) Comparison of corneal biomechanics between low and high myopic eyes-a meta-analysis. Am J Ophthalmol 207:419–425

    Article  PubMed  Google Scholar 

  7. Kang BS, Wang LK, Zheng YP, Guggenheim JA, Stell WK, Kee C (2018) High myopia induced by form deprivation is associated with altered corneal biomechanical properties in chicks. PLoS One 13(11):e0207189

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chang L, Pan CW, Ohno-Matsui K, Lin X, Cheung GC, Gazzard G, Koh V, Hamzah H, Tai ES, Lim SC et al (2013) Myopia-related fundus changes in Singapore adults with high myopia. Am J Ophthalmol 155(6):991-999 e991

    Article  PubMed  Google Scholar 

  9. Harper AR, Summers JA (2015) The dynamic sclera: extracellular matrix remodeling in normal ocular growth and myopia development. Exp Eye Res 133:100–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Han F, Li M, Wei P, Ma J, Jhanji V, Wang Y (2020) Effect of biomechanical properties on myopia: a study of new corneal biomechanical parameters. BMC Ophthalmol 20(1):459

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sedaghat MR, Momeni-Moghaddam H, Azimi A, Fakhimi Z, Ziaei M, Danesh Z, Roberts CJ, Monfared N, Jamali (2020) Corneal biomechanical properties in varying severities of myopia. Front Bioeng Biotechnol 8:595330

    Article  PubMed  Google Scholar 

  12. Ni Y, Wang L, Liu C, Li Z, Yang J, Zeng J (2022) Gene expression profile analyses to identify potential biomarkers for myopia. Eye (Lond) 37(6):1264–1270

  13. Wu W, Wang Y, Zhang H, Zhang J, Li H, Dou (2016) One-year visual outcome of small incision lenticule extraction (SMILE) surgery in high myopic eyes: retrospective cohort study. BMJ Open 6(9):e010993

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M (2022) KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res 51(D1):D587–D592

  15. He Q, Fang X, Zhu T, Han S, Zhu H, Li S (2019) Differential proteomics based on TMT and PRM reveal the resistance response of Bambusa pervariabilis x Dendrocalamopisis grandis induced by AP-toxin. Metabolites 9(8):166

  16. Shi T, Song E, Nie S, Rodland KD, Liu T, Qian WJ, Smith RD (2016) Advances in targeted proteomics and applications to biomedical research. Proteomics 16(15–16):2160–2182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gallien S, Kim SY, Domon B (2015) Large-scale targeted proteomics using internal standard triggered-parallel reaction monitoring (IS-PRM). Mol Cell Proteomics 14(6):1630–1644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Trost A, Desch P, Wally V, Haim M, Maier RH, Reitsamer HA, Hintner H, Bauer JW, Onder K (2010) Aberrant heterodimerization of keratin 16 with keratin 6A in HaCaT keratinocytes results in diminished cellular migration. Mech Ageing Dev 131(5):346–353

    Article  CAS  PubMed  Google Scholar 

  19. Chan JKL, Yuen D, Too PH, Sun Y, Willard B, Man D, Tam C (2018) Keratin 6a reorganization for ubiquitin-proteasomal processing is a direct antimicrobial response. J Cell Biol 217(2):731–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Radaev S, Sun P (2002) Recognition of immunoglobulins by Fcgamma receptors. Mol Immunol 38(14):1073–1083

    Article  CAS  PubMed  Google Scholar 

  21. McKay TB, Hutcheon AEK, Zieske JD (2020) Biology of corneal fibrosis: soluble mediators, integrins, and extracellular vesicles. Eye (Lond) 34(2):271–278

    Article  PubMed  Google Scholar 

  22. Semba RD, Enghild JJ, Venkatraman V, Dyrlund TF, Van Eyk JE (2013) The human eye proteome project: perspectives on an emerging proteome. Proteomics 13(16):2500–2511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Li Q, Zhu H, Fan M, Sun J, Reinach PS, Wang Y, Qu J, Zhou X, Zhao F (2022) Form-deprivation myopia downregulates calcium levels in retinal horizontal cells in mice. Exp Eye Res 218:109018

    Article  CAS  PubMed  Google Scholar 

  24. Halasa AH, McLaren DS (1964) The refractive state of malnourished children. Arch Ophthalmol 71:827–831

    Article  CAS  PubMed  Google Scholar 

  25. Pan M, Zhao F, Xie B, Wu H, Zhang S, Ye C, Guan Z, Kang L, Zhang Y, Zhou X et al (2021) Dietary omega-3 polyunsaturated fatty acids are protective for myopia. Proc Natl Acad Sci USA 118(43):e2104689118

  26. Cao J, Routh AL, Kuyumcu-Martinez MN (2021) Nanopore sequencing reveals full-length tropomyosin 1 isoforms and their regulation by RNA-binding proteins during rat heart development. J Cell Mol Med 25(17):8352–8362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lippmann T, Jonkisz A, Dobosz T, Petrasch-Parwez E, Epplen JT, Dekomien G (2007) Haplotype-defined linkage region for gPRA in Schapendoes dogs. Mol Vis 13:174–180

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Nakajima Y, Moriyama M, Hattori M, Minato N, Nakanishi S (2009) Isolation of ON bipolar cell genes via hrGFP-coupled cell enrichment using the mGluR6 promoter. J Biochem 145(6):811–818

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Thanks for Tianjin Eye Hospital for providing the study subjects.

Funding

This study was funded by the National Natural Science Foundation of China (Grant No. 81900828, Wenjing Wu) and the Beijing Municipal Commission of Science and Technology Capital Clinical Diagnosis and Treatment Technology Research and Transformation Application (Grant Number Z201100005520043, Fengju Zhang).

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Authors and Affiliations

Authors

Contributions

Wenjing Wu: study design; data collection, analysis and interpretation, and writing and revising the manuscript. Yushan Xu: revising the manuscript. Fengju Zhang: funding collection, study design, data analysis, and revising the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fengju Zhang.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board (IRB) of Tianjin Eye Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors.

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The authors declare no competing interests.

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Wu, W., Xu, Y. & Zhang, F. Comparisons of the protein expressions between high myopia and moderate myopia on the anterior corneal stroma in human. Graefes Arch Clin Exp Ophthalmol 261, 3549–3558 (2023). https://doi.org/10.1007/s00417-023-06158-2

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  • DOI: https://doi.org/10.1007/s00417-023-06158-2

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