Evidence map›Paper›PMID 34795670›Full record

ArticleFrontiers in immunology2021

In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy.

Stefaniya Konstantinova Boneva, Julian Wolf, Rozina Ida Hajdú, Gabriele Prinz, Henrike Salié, Anja Schlecht, Saskia Killmer, Yannik Laich, Henrik Faatz, Albrecht Lommatzsch and 8 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  14. Review
  15. Article
  16. Article
  17. Hyalocytes-guardians of the vitreoretinal interface.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024
    Review
  18. Article
  19. Review
  20. Macrophage activation contributes to diabetic retinopathy.Journal of molecular medicine (Berlin, Germany) · 2024
    Review
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

18 authors at 4 institutions in 2 countries.

Stefaniya Konstantinova BonevaEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Julian WolfEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Rozina Ida HajdúEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Gabriele PrinzEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Henrike SaliéDepartment of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Anja SchlechtEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Saskia KillmerDepartment of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Yannik LaichEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Henrik FaatzSt. Franziskus Eye Center, Münster, Germany.
Albrecht LommatzschSt. Franziskus Eye Center, Münster, Germany.
Martin BuschDepartment of Ophthalmology, University Medical Center Greifswald, Greifswald, Germany.
Felicitas BucherEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Andreas StahlDepartment of Ophthalmology, University Medical Center Greifswald, Greifswald, Germany.
Daniel BöhringerEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Bertram BengschDepartment of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Günther SchlunckEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Hansjürgen AgostiniEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Clemens A K LangeEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
University Medical Center Freiburg · DESt. Franziskus Hospital · DEUniversitätsmedizin Greifswald · DEUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Retinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR. Methods: A total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease. Results: The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR. Conclusion: This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach.

Indexed as

Cell TransdifferentiationAdultAgedCells, CulturedComputational BiologyDiabetic RetinopathyDrug RepositioningEndothelial CellsEpiretinal MembraneEye ProteinsFemaleGene OntologyHumansImatinib MesylateImmunologic FactorsMaleEye ProteinsImatinib MesylateImmunologic FactorshyalocytesImaging Mass Cytometrymyofibroblastsproliferative diabetic retinopathy (PDR)retinal neovascularization (RNV)RNA sequencingtransdifferentiation

Identifiers

PMID34795670
PMCPMC8593213
OpenAlexW3208964757

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.