Evidence map›Paper›PMID 35429992›Full record

ArticleCell death discovery2022

Vascular derived endothelin receptor A controls endothelin-induced retinal ganglion cell death.

Olivia J Marola, Gareth R Howell, Richard T Libby

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
4.9field-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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. IL1A enhances TNF-induced retinal ganglion cell death.Frontiers in aging neuroscience · 2026
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  14. Endothelin-1, over-expressed in SOD1Frontiers in cellular neuroscience · 2022
    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

3 authors at 2 institutions in 1 country.

Olivia J MarolaDepartment of Ophthalmology, Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY, USA.ORCID http://orcid.org/0000-0002-0078-6088
Gareth R HowellThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, USA.
Richard T LibbyDepartment of Ophthalmology, Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY, USA. richard_libby@urmc.rochester.edu.ORCID http://orcid.org/0000-0003-2844-7632
University of Rochester Medical Center · USJackson Laboratory · US

Funding

The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Paul Richard Territo · 2016 to 2026
$95.6M
TREAT AD Structural Biology CoreU54AG065187 · NIA · EMORY UNIVERSITY · PI Gregory W Carter, ALLAN I LEVEY · 2019 to 2026
$69.7M
VISUAL SCIENCET32EY007125 · NEI · UNIVERSITY OF ROCHESTER · PI Krystel R Huxlin, Duje Tadin · 1990 to 2026
$7.1M
Cell specific roles of the endothelin system in glaucoma-relevant retinal ganglion cell deathR01EY027701 · NEI · UNIVERSITY OF ROCHESTER · PI HOWELL, GARETH R, LIBBY, RICHARD T · 2017 to 2021
$2.7M
Endothelin Signaling in Glaucomatous NeurodegenerationF31EY030739 · NEI · UNIVERSITY OF ROCHESTER · PI MAROLA, OLIVIA JOYCE · 2020 to 2021
$85k
NEI NIH HHS F31 EY030739NEI NIH HHS R01 EY027701NEI NIH HHS T32 EY007125NIA NIH HHS U54 AG054345NIA NIH HHS U54 AG065187U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY027701U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY030739
6 · The paper itself

Abstract

Endothelin (EDN, also known as ET) signaling has been suggested to be an important mediator of retinal ganglion cell (RGC) death in glaucoma. Antagonism of EDN receptors (EDNRA and EDNRB, also known as ET-A and ET-B) prevented RGC death in mouse models of chronic ocular hypertension, and intravitreal injection of EDN ligand was sufficient to drive RGC death. However, it remains unclear which cell types EDN ligands directly affect to elicit RGC death. Multiple cell types in the retina and optic nerve express EDNRA and EDNRB and thus could respond to EDN ligands in the context of glaucoma. Here, we systematically deleted Edn receptors from specific cell types to identify the critical EDN receptor mediating RGC death in vivo. Deletion of both Ednra and Ednrb from retinal neurons (including RGCs) and macroglia did not prevent RGC loss after exposure to EDN1 ligands, suggesting EDN1 ligands cause RGC death via an indirect mechanism involving a secondary cell type. Deletion of Ednra from the full body, and then specifically from vascular mural cells, prevented EDN1-induced vasoconstriction and RGC death. Together, these data suggest EDN ligands cause RGC death via a mechanism initiated by vascular mural cells. It is possible RGC death is a consequence of vascular mural cell-induced vasoconstriction and its pathological sequelae. These results highlight the potential importance of neurovascular dysfunction in glaucoma.

Identifiers

PMID35429992
PMCPMC9013356
OpenAlexW4224075319

What OpenQuestion holds

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Read underepoch 390

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.