Evidence map›Paper›PMID 21562271›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011

The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells.

Daniel A Ryskamp, Paul Witkovsky, Peter Barabas, Wei Huang, Christopher Koehler, Nikolay P Akimov, Suk Hee Lee, Shiwani Chauhan, Wei Xing, René C Rentería and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed
6.0field-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

138 citing papers in PubMed, 227 citations in OpenAlex.

  1. Article
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  3. Review
  4. Article
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  8. Article
  9. Frontiers in cell and developmental biology · 2025
    Review
  10. Review
  11. Review
  12. Mechanobiology in the eye.npj biological physics and mechanics · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. The Variety of Mechanosensitive Ion Channels in Retinal Neurons.International journal of molecular sciences · 2024
    Review
  17. Review
  18. Article
  19. Review
  20. Article

78 more citing papers are in PubMed but not listed here.

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

12 authors at 6 institutions in 2 countries.

Daniel A RyskampDepartment of Ophthalmology & Visual Sciences, John A. Moran Eye Center, Interdepartmental Program in Neuroscience, and Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Paul Witkovsky
Peter Barabas
Wei Huang
Christopher Koehler
Nikolay P Akimov
Suk Hee Lee
Shiwani Chauhan
Wei Xing
René C Rentería
Wolfgang Liedtke
David Krizaj
The University of Texas Health Science Center at San Antonio · USUniversity of Utah · USEye Center · SADuke Medical Center · USDuke University · USNew York University · US

Funding

University of Utah, Core Vision Research GrantP30EY014800 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI PAUL STEVEN BERNSTEIN · 2005 to 2026
$14.6M
REGULATION OF NEUROTRANSMISSION IN THE RETINAR01EY013870 · NEI · UNIVERSITY OF UTAH · PI KRIZAJ, DAVID · 2002 to 2011
$2.7M
Predoctoral Interdepartmental Training Program in NeuroscienceT32DC008553 · NIDCD · UNIVERSITY OF UTAH · PI LUCERO, MARY T · 2006 to 2010
$906k
NEI NIH HHS P30 EY014800NEI NIH HHS P30EY014800NEI NIH HHS R01 EY013870NEI NIH HHS R01EY13870NIDCD NIH HHS T32 DC008553NIDCD NIH HHS T32DC008553
6 · The paper itself

Abstract

Sustained increase in intraocular pressure represents a major risk factor for eye disease, yet the cellular mechanisms of pressure transduction in the posterior eye are essentially unknown. Here we show that the mouse retina expresses mRNA and protein for the polymodal transient receptor potential vanilloid 4 (TRPV4) cation channel known to mediate osmotransduction and mechanotransduction. TRPV4 antibodies labeled perikarya, axons, and dendrites of retinal ganglion cells (RGCs) and intensely immunostained the optic nerve head. Müller glial cells, but not retinal astrocytes or microglia, also expressed TRPV4 immunoreactivity. The selective TRPV4 agonists 4α-PDD and GSK1016790A elevated [Ca2+]i in dissociated RGCs in a dose-dependent manner, whereas the TRPV1 agonist capsaicin had no effect on [Ca2+](RGC). Exposure to hypotonic stimulation evoked robust increases in [Ca2+](RGC). RGC responses to TRPV4-selective agonists and hypotonic stimulation were absent in Ca2+ -free saline and were antagonized by the nonselective TRP channel antagonists Ruthenium Red and gadolinium, but were unaffected by the TRPV1 antagonist capsazepine. TRPV4-selective agonists increased the spiking frequency recorded from intact retinas recorded with multielectrode arrays. Sustained exposure to TRPV4 agonists evoked dose-dependent apoptosis of RGCs. Our results demonstrate functional TRPV4 expression in RGCs and suggest that its activation mediates response to membrane stretch leading to elevated [Ca2+]i and augmented excitability. Excessive Ca2+ influx through TRPV4 predisposes RGCs to activation of Ca2+ -dependent proapoptotic signaling pathways, indicating that TRPV4 is a component of the response mechanism to pathological elevations of intraocular pressure.

Indexed as

AnimalsApoptosisAxonsCalciumCapsaicinDendritesDose-Response Relationship, DrugElectrophysiologyImmunohistochemistryLeucineMechanotransduction, CellularMiceRetinal Ganglion CellsRNA, MessengerSulfonamidesTRPV Cation ChannelsCalciumCapsaicinLeucineN-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamideRNA, MessengerSulfonamidesTrpv4 protein, mouseTRPV Cation Channels

Identifiers

PMID21562271
PMCPMC3109951
OpenAlexW2015948778

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.