Evidence map›Paper›PMID 34231253›Full record

ArticleGlia2021

Cannabinoid signaling promotes the de-differentiation and proliferation of Müller glia-derived progenitor cells.

Warren A Campbell, Sydney Blum, Alana Reske, Thanh Hoang, Seth Blackshaw, Andy J Fischer

Open access · greenAbstract read
In one paragraph

Article in Glia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024
    Review
  17. Article
  18. Article
  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 2 institutions in 1 country.

Warren A CampbellDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0003-4913-5945
Sydney BlumDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Alana ReskeDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Thanh HoangSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Seth BlackshawSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-1338-8476
Andy J FischerDepartment of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0001-6123-7405
The Ohio State University · USJohns Hopkins University · US

Funding

Muller glia: roles in retinal homeostasis and neuronal regenerationR01EY022030 · NEI · OHIO STATE UNIVERSITY · PI FISCHER, ANDY J · 2012 to 2021
$3.5M
Comparative transcriptomic and epigenomic analyses of Muller glia reprogrammingU01EY027267 · NEI · UNIVERSITY OF NOTRE DAME · PI BLACKSHAW, SETH, HYDE, DAVID R · 2016 to 2019
$3.0M
Identification of gene regulatory networks that control proliferative and neurogenic competence in mammalian Müller gliaR01EY031685 · NEI · JOHNS HOPKINS UNIVERSITY · PI BLACKSHAW, SETH · 2020 to 2023
$2.0M
Fatty acid binding-proteins and endocannabinoids in the retina; roles in glial reactivity and reprogramming of Muller glia into progenitor cellsR01EY032141 · NEI · OHIO STATE UNIVERSITY · PI FISCHER, ANDY J · 2021 to 2025
$1.9M
NEI NIH HHS R01 EY022030NEI NIH HHS R01 EY031685NEI NIH HHS R01 EY032141NEI NIH HHS U01 EY027267
6 · The paper itself

Abstract

Endocannabinoids (eCB) are lipid-based neurotransmitters that are known to influence synaptic function in the visual system. eCBs are also known to suppress neuroinflammation in different pathological states. However, nothing is known about the roles of the eCB system during the transition of Müller glia (MG) into proliferating progenitor-like cells in the retina. Accordingly, we used the chick and mouse model to characterize expression patterns of eCB-related genes and applied pharmacological agents to investigate how the eCB system impacts glial reactivity and the capacity of MG to become Müller glia-derived progenitor cells (MGPCs). We queried single cell RNA-seq libraries to identify eCB-related genes and identify cells with dynamic patterns of expression in damaged retinas. MG and inner retinal neurons expressed the eCB receptor CNR1, as well as enzymes involved in eCB metabolism. In the chick, intraocular injections of cannabinoids, 2-Arachidonoylglycerol (2-AG) and Anandamide (AEA), stimulated the formation of MGPCs. Cannabinoid Receptor 1 (CNR1)-agonists and Monoglyceride Lipase-inhibitor promoted the formation of MGPCs, whereas CNR1-antagonist and inhibitors of eCB synthesis suppressed this process. In damaged mouse retinas where MG activate NFkB-signaling, activation of CNR1 decreased and inhibition of CNR1 increased NFkB, whereas levels of neuronal cell death were unaffected. Surprisingly, retinal microglia were largely unaffected by increases or decreases in eCB-signaling in both chick and mouse retinas. We conclude that the eCB system in the retina influences the reactivity of MG and the formation of proliferating MGPCs, but does not influence the reactivity of immune cells in the retina.

Indexed as

CannabinoidsStem CellsAnimalsCell ProliferationEpendymoglial CellsMiceNeurogliaRetinaCannabinoidsendocannabinoidsmicrogliaMüller gliaMüller glia-derived progenitor cellsscRNA-seq

Identifiers

PMID34231253
PMCPMC8373766
OpenAlexW3178419038

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.