Evidence mapPaperPMID 41268978Full record

ArticleInvestigative ophthalmology & visual science2025

Mechano- and Glucocorticoid-Sensitive TREK-1 Channels Regulate Conventional Outflow and Intraocular Pressure.

Sarah N Redmon, Oleg Yarishkin, Christopher N Rudzitis, Monika Lakk, Jacques Bertrand, Joseph van Batenburg-Sherwood, Christina M Nicou, Christopher L Passaglia, Darryl R Overby, David Križaj

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

10 authors.

Sarah N RedmonDepartment of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States.
Oleg YarishkinDepartment of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States.
Christopher N RudzitisDepartment of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States.
Monika LakkDepartment of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States.
Jacques BertrandDepartment of Bioengineering, Imperial College London, London, United Kingdom.
Joseph van Batenburg-SherwoodDepartment of Bioengineering, Imperial College London, London, United Kingdom.
Christina M NicouDepartment of Medical Engineering, University of South Florida, Tampa, Florida, United States.
Christopher L PassagliaDepartment of Medical Engineering, University of South Florida, Tampa, Florida, United States.
Darryl R OverbyDepartment of Bioengineering, Imperial College London, London, United Kingdom.
David KrižajDepartment of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States.

Funding

University of Utah Core Vision Research GrantP30EY014800 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2005 to 2025
$1.4M
Replacement of the Flexcell Tension systemR01EY027920 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2025 to 2025
$443k
Vision Research Training Grant at the University of UtahT32EY024234 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2025 to 2025
$161k
NEI NIH HHS P30 EY014800NEI NIH HHS R01 EY022076NEI NIH HHS R01 EY027920NEI NIH HHS R01 EY031817NEI NIH HHS T32 EY024234
6 · The paper itself

Abstract

Purpose: The purpose of this study was twofold: to determine the molecular link between corticosteroid exposure and mechanosensation and to establish the role of mechanosensitive TWIK-related potassium channel-1 (TREK-1) in the regulation of aqueous humor outflow and corticosteroid-induced ocular hypertension (OHT). Methods: Real-time PCR was used to determine the corticosteroid dexamethasone (DEX) dependence of expression of tandem-pore potassium (K2P), transient receptor potential vanilloid (TRPV), Piezo channel, extracellular matrix (ECM), and fibrotic marker genes in mouse trabecular meshwork (mTM) cells. Immunohistochemistry was employed to assess TREK-1 localization, iPerfusion to determine the TREK-1 dependence of conventional outflow, and tonometry to track intraocular pressure (IOP) in mouse eyes. Telemetry additionally tested TREK-1 dependence of OHT in rat. Steroid-induced transcriptional suppression of mTM Kcnk2 was validated by whole-cell recording in primary human trabecular meshwork (TM) cells. Results: The tandem pore K+ channel transcriptome in mTM cells was dominated by Trek-1 (Kcnk2) mRNA; with residual levels of Traak and Thik-2 transcripts; and low levels of Trek-2, Twik3, and Task1 expression. DEX upregulated Fsp1 and suppressed Kcnk2 expression without affecting Trpv4, Piezo1, or Trpc1 mRNA content. The TREK-1 agonist ML-402 doubled outflow facility in mouse eyes and reduced IOP in the mouse model of DEX-induced OHT and in rat eyes with spontaneously elevated IOP. Chronic DEX exposure depolarized human primary TM (pTM) cells and reduced the amplitude of the ML-402-evoked current. Conclusions: Ocular overexposure to corticosteroids may compromise IOP homeostasis by impairing TM expression and function of TREK-1. Pharmacological activation of TREK-1 facilitates conventional outflow and could help lower IOP in eyes with steroid-induced ocular hypertension.

Indexed as

Aqueous HumorGene Expression RegulationGlucocorticoidsIntraocular PressureOcular HypertensionPotassium Channels, Tandem Pore DomainTrabecular MeshworkAnimalsCells, CulturedDexamethasoneDisease Models, AnimalHumansImmunohistochemistryMaleMechanotransduction, CellularMiceDexamethasoneGlucocorticoidspotassium channel protein TREK-1Potassium Channels, Tandem Pore DomainTRPV Cation Channels

Identifiers

PMID41268978
PMCPMC12663879

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.