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Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis

  • Bent Honoré EMAIL logo , Javad Nouri Hajari , Tobias Torp Pedersen , Tomas Ilginis , Hajer Ahmad Al-Abaiji , Claes Sepstrup Lønkvist , Jon Peiter Saunte , Dorte Aalund Olsen , Ivan Brandslund , Henrik Vorum and Carina Slidsborg EMAIL logo
Published/Copyright: February 9, 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 6

Abstract

Objectives

To identify molecular pathways and prognostic- and diagnostic plasma-protein biomarkers for diabetic retinopathy at various stages.

Methods

This exploratory, cross-sectional proteomics study involved plasma from 68 adults, including 15 healthy controls and 53 diabetes patients for various stages of diabetic retinopathy: non-diabetic retinopathy, non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and diabetic macular edema. Plasma was incubated with peptide library beads and eluted proteins were tryptic digested, analyzed by liquid chromatography-tandem mass-spectrometry followed by bioinformatics.

Results

In the 68 samples, 248 of the 731 identified plasma-proteins were present in all samples. Analysis of variance showed differential expression of 58 proteins across the five disease subgroups. Protein–Protein Interaction network (STRING) showed enrichment of various pathways during the diabetic stages. In addition, stage-specific driver proteins were detected for early and advanced diabetic retinopathy. Hierarchical clustering showed distinct protein profiles according to disease severity and disease type.

Conclusions

Molecular pathways in the cholesterol metabolism, complement system, and coagulation cascade were enriched in patients at various stages of diabetic retinopathy. The peroxisome proliferator-activated receptor signaling pathway and systemic lupus erythematosus pathways were enriched in early diabetic retinopathy. Stage-specific proteins for early – and advanced diabetic retinopathy as determined herein could be ‘key’ players in driving disease development and potential ‘target’ proteins for future therapies. For type 1 and 2 diabetes mellitus, the proteomic profiles were especially distinct during the early disease stage. Validation studies should aim to clarify the role of the detected molecular pathways, potential biomarkers, and potential ‘target’ proteins for future therapies in diabetic retinopathy.

Keywords: liquid chromatography-tandem mass spectrometry; proteomics; disease mechanisms; plasma-protein biomarkers; diabetic retinopathy
Corresponding authors: Bent Honoré, MD, D.M.Sc., Department of Biomedicine, Aarhus University, Ole Worm Allé 4, 8000 Aarhus C, Denmark; and Department of Clinical Medicine, Aalborg University, Aalborg, Denmark, E-mail: ; and Carina Slidsborg, MD, PhD, Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Valdemar Hansens Vej 1, 2600 Glostrup, Copenhagen, Denmark, E-mail:

Funding source: Dagmar Marshalls Fond

Funding source: Vissing Fonden

Funding source: A. P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal

Funding source: Einar Willumsens Foundation

Funding source: Kong Christian den Tiendes Foundation

Funding source: Aase and Ejnar Danielsens Foundation

Funding source: August Frederik Wedell Erichsens Foundation

Funding source: Synoptik Foundation

Funding source: Fight for Sight Denmark

Acknowledgments

We are grateful to Ahmed Basim Abduljabar and Mona Britt Hansen for expert technical assistance.

  1. Research ethics: The present study was approved by the Danish Ethics Committee (H-17034984) and the Data Protection Agency.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: BH has stocks in Novo Nordisk A/S. CS consultancy for Bayer and Regeneron, and former employee of Novo Nordisk A/S. CSL advisory board for Bayer. Otherwise, authors state no conflict of interest.

  5. Research funding: This work was supported by grants from Aase and Ejnar Danielsens Fond, Fight for Sight Denmark, Dagmar Marshalls Fond, Einar Willumsens Fond, August Frederik Wedell Erichsens Fond, Kong Christian den Tiendes Fond, The Synoptikfonden and Vissing Fonden. The mass spectrometry instrumentation was kindly donated by A. P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal. The sponsors or funding organizations had no role in the design or conduct of this research.

  6. Data availability: The raw data can be obtained on request from the corresponding author.

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Received: 2023-04-26
Accepted: 2024-01-16
Published Online: 2024-02-09
Published in Print: 2024-05-27

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-1128
Keywords for this article
liquid chromatography-tandem mass spectrometry; proteomics; disease mechanisms; plasma-protein biomarkers; diabetic retinopathy

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  33. The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study
  34. Development and evaluation of a CRISPR-Cas13a system-based diagnostic for hepatitis E virus
  35. Letters to the Editor
  36. Crioplast® is a reliable device to ensure pre-analytical stability of adrenocorticotrophin (ACTH)
  37. Falsely decreased Abbott Alinity-c gamma-glutamyl transferase-2 result from paraprotein and heparin interference: case report and subsequent laboratory experiments
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  39. Value of plasma neurofilament light chain for monitoring efficacy in children with later-onset spinal muscular atrophy under nusinersen treatment
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  42. Congress Abstracts
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  44. 14th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  45. 15th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  46. ISMD2024 Thirteenth International Symposium on Molecular Diagnostics
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