Evidence map›Paper›PMID 34776983›Full record

ArticleFrontiers in pharmacology2021

Proteomic Phenotyping of Stimulated Müller Cells Uncovers Profound Pro-Inflammatory Signaling and Antigen-Presenting Capacity.

Adrian Schmalen, Lea Lorenz, Antje Grosche, Diana Pauly, Cornelia A Deeg, Stefanie M Hauck

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026
    Review
  4. Article
  5. Article
  6. Tear fluid participates in systemic immunity.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Review
  7. Early-stage diabetic retinopathy: gut-metabolic triggers, immune-neurodegeneration, and interventions.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025
    Review
  8. Article
  9. Article
  10. Interferons andFrontiers in immunology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. NMOSD IgG Impact Retinal Cells in Murine Retinal Explants.Current issues in molecular biology · 2023
    Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Adrian SchmalenResearch Unit Protein Science and Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Lea LorenzChair of Physiology, Department of Veterinary Sciences, LMU Munich, Martinsried, Germany.
Antje GroscheDepartment of Physiological Genomics, Biomedical Center, LMU Munich, Martinsried, Germany.
Diana PaulyExperimental Ophthalmology, Philipps-University Marburg, Marburg, Germany.
Cornelia A DeegChair of Physiology, Department of Veterinary Sciences, LMU Munich, Martinsried, Germany.
Stefanie M HauckResearch Unit Protein Science and Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Ludwig-Maximilians-Universität München · DEHelmholtz Zentrum München · DEUniversity Hospital Regensburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Müller cells are the main macroglial cells of the retina exerting a wealth of functions to maintain retinal homoeostasis. Upon pathological changes in the retina, they become gliotic with both protective and detrimental consequences. Accumulating data also provide evidence for a pivotal role of Müller cells in the pathogenesis of diabetic retinopathy (DR). While microglial cells, the resident immune cells of the retina are considered as main players in inflammatory processes associated with DR, the implication of activated Müller cells in chronic retinal inflammation remains to be elucidated. In order to assess the signaling capacity of Müller cells and their role in retinal inflammation, we performed in-depth proteomic analysis of Müller cell proteomes and secretomes after stimulation with INFγ, TNFα, IL-4, IL-6, IL-10, VEGF, TGFβ1, TGFβ2 and TGFβ3. We used both, primary porcine Müller cells and the human Müller cell line MIO-M1 for our hypothesis generating approach. Our results point towards an intense signaling capacity of Müller cells, which reacted in a highly discriminating manner upon treatment with different cytokines. Stimulation of Müller cells resulted in a primarily pro-inflammatory phenotype with secretion of cytokines and components of the complement system. Furthermore, we observed evidence for mitochondrial dysfunction, implying oxidative stress after treatment with the various cytokines. Finally, both MIO-M1 cells and primary porcine Müller cells showed several characteristics of atypical antigen-presenting cells, as they are capable of inducing MHC class I and MHC class II with co-stimulatory molecules. In line with this, they express proteins associated with formation and maturation of phagosomes. Thus, our findings underline the importance of Müller cell signaling in the inflamed retina, indicating an active role in chronic retinal inflammation.

Indexed as

atypical antigen-presenting cellcomplement systemcytokinesdiabetic retinopathyimmune responseMüller cellsoxidative phosphorylationretina

Identifiers

PMID34776983
PMCPMC8585775
OpenAlexW3211283940

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.