Evidence map›Paper›PMID 27006502›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Differential volume regulation and calcium signaling in two ciliary body cell types is subserved by TRPV4 channels.

Andrew O Jo, Monika Lakk, Amber M Frye, Tam T T Phuong, Sarah N Redmon, Robin Roberts, Bruce A Berkowitz, Oleg Yarishkin, David Križaj

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

49 citing papers in PubMed, 65 citations in OpenAlex.

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  19. Mutation of the TRPM3 cation channel underlies progressive cataract development and lens calcification associated with pro-fibrotic and immune cell responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Andrew O JoDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132;
Monika LakkDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132;
Amber M FryeDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132;
Tam T T PhuongDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132;
Sarah N RedmonDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132;
Robin RobertsDepartment of Anatomy and Cell Biology, Wayne State University, Detroit, MI 48202;
Bruce A BerkowitzDepartment of Anatomy and Cell Biology, Wayne State University, Detroit, MI 48202; Department of Ophthalmology, Wayne State University, Detroit, MI 48202;
Oleg YarishkinDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132;
David KrižajDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132; Center for Translational Medicine, Moran Eye Institute, University of Utah, Salt Lake City, UT 84132; Department of Neurobiology & Anatomy, University of Utah, Salt Lake City, UT 84132; Department of Bioengineering, University of Utah, Salt Lake City, UT 84132 david.krizaj@hsc.utah.edu.
University of Utah · USWayne State University · USEye Institute of Utah · US

Funding

University of Utah, Core Vision Research GrantP30EY014800 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Bryan William Jones · 2005 to 2026
$14.6M
Replacement of the Flexcell Tension systemR01EY027920 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI DAVID KRIZAJ · 2017 to 2026
$3.5M
The role of mechanosensation in the vertebrate retinaR01EY022076 · NEI · UNIVERSITY OF UTAH · PI KRIZAJ, DAVID · 2013 to 2017
$1.9M
Role of calcium channels in the development of diabetic retinopathyR21EY021619 · NEI · WAYNE STATE UNIVERSITY · PI BERKOWITZ, BRUCE A. · 2014 to 2015
$413k
NEI NIH HHS P30 EY014800NEI NIH HHS R01 EY022076NEI NIH HHS R01 EY027920NEI NIH HHS R21 EY021619
6 · The paper itself

Abstract

Fluid secretion by the ciliary body plays a critical and irreplaceable function in vertebrate vision by providing nutritive support to the cornea and lens, and by maintaining intraocular pressure. Here, we identify TRPV4 (transient receptor potential vanilloid isoform 4) channels as key osmosensors in nonpigmented epithelial (NPE) cells of the mouse ciliary body. Hypotonic swelling and the selective agonist GSK1016790A (EC50 ∼33 nM) induced sustained transmembrane cation currents and cytosolic [Formula: see text] elevations in dissociated and intact NPE cells. Swelling had no effect on [Formula: see text] levels in pigment epithelial (PE) cells, whereas depolarization evoked [Formula: see text] elevations in both NPE and PE cells. Swelling-evoked [Formula: see text] signals were inhibited by the TRPV4 antagonist HC067047 (IC50 ∼0.9 μM) and were absent in Trpv4(-/-) NPE. In NPE, but not PE, swelling-induced [Formula: see text] signals required phospholipase A2 activation. TRPV4 localization to NPE was confirmed with immunolocalization and excitation mapping approaches, whereas in vivo MRI analysis confirmed TRPV4-mediated signals in the intact mouse ciliary body. Trpv2 and Trpv4 were the most abundant vanilloid transcripts in CB. Overall, our results support a model whereby TRPV4 differentially regulates cell volume, lipid, and calcium signals in NPE and PE cell types and therefore represents a potential target for antiglaucoma medications.

Indexed as

AnimalsCalciumCalcium SignalingCells, CulturedCell SizeCiliary BodyEnzyme ActivationEpithelial CellsEpitheliumGlaucomaLeucineMiceMice, Inbred C57BLMice, KnockoutOsmotic PressurePhospholipases A2CalciumLeucineN-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamidePhospholipases A2SulfonamidesTrpv4 protein, mouseTRPV Cation Channelsaqueous humorciliary bodyglaucomaintraocular pressureTRPV4

Identifiers

PMID27006502
PMCPMC4833269
OpenAlexW2307934897

What OpenQuestion holds

Textmetadata
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.