Evidence map›Paper›PMID 24374036›Full record

ArticleExperimental eye research2014

Concentration-related effects of nitric oxide and endothelin-1 on human trabecular meshwork cell contractility.

W Michael Dismuke, Jin Liang, Darryl R Overby, W Daniel Stamer

Abstract read
In one paragraph

Article in Experimental eye research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
9.4field-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

60 citing papers in PubMed, 108 citations in OpenAlex.

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  9. The Factors Affecting the Stability of IOP Homeostasis.Investigative ophthalmology & visual science · 2024
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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

4 authors at 2 institutions in 2 countries.

W Michael DismukeDepartment of Ophthalmology, Duke University, Durham, NC, USA.
Jin LiangDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Darryl R OverbyDepartment of Bioengineering, Imperial College London, London, UK.
W Daniel StamerDepartment of Ophthalmology, Duke University, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA. Electronic address: dan.stamer@duke.edu.
Duke University · USImperial College London · GB

Funding

eNOS-Dependent Mechanoregulation of Intraocular PressureR01EY022359 · NEI · DUKE UNIVERSITY · PI STAMER, W DANIEL · 2012 to 2025
$5.6M
NEI NIH HHS EY022359NEI NIH HHS R01 EY022359
6 · The paper itself

Abstract

The contractility status of trabecular meshwork (TM) cells influences aqueous humor outflow resistance and intraocular pressure. Using human TM cells as a model, the goal of the present study was to examine concentration-response relationships of two prototypical molecules, nitric oxide (NO) and endothelin-1 (ET-1), known to differentially influence vascular smooth muscle contractility. Efficacy of ET-1, two NO donors (DETA-NO and SNP) and a cGMP analog (8-Br-cGMP) were assessed using two complementary methods: functionally in a gel contraction assay and biochemically using a myosin light chain phosphorylation assay. The NO donors DETA-NO and SNP dose dependently relaxed cultured human TM cells (EC50 for DETA-NO = 6.0 ± 2.4 μM, SNP = 12.6 ± 8.8 μM), with maximum effects at 100 μM. Interestingly, at concentrations of NO donors above 100 μM, the relaxing effect was lost. Relaxation caused by DETA-NO (100 μM) was dose dependently blocked by the soluble guanylate cyclase specific inhibitor ODQ (IC50 = 460 ± 190 nM). In contrast to the NO donors, treatment of cells with the cGMP analog, 8-Br-cGMP produced the largest relaxation (109.4%) that persisted at high concentrations (EC50 = 110 ± 40 μM). ET-1 caused a dose-dependent contraction of human TM cells (EC50 = 1.5 ± 0.5 pM), with maximum effect at 100 pM (56.1%) and this contraction was reversed by DETA-NO (100 μM). Consistent with functional data, phosphorylation status of myosin light chain was dose dependently reduced with DETA-NO, and increased with ET-1. Together, data show that TM cells rapidly change their contractility status over a wide dynamic range, well suited for the regulation of outflow resistance and intraocular pressure.

Indexed as

AdultCell Physiological PhenomenaCells, CulturedCyclic GMPDose-Response Relationship, DrugEndothelin-1Enzyme InhibitorsGuanylate CyclaseHumansInfantMiddle AgedMyosin Light ChainsNitric Oxide DonorsNitroprussideOxadiazolesPhosphorylation1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene8-bromocyclic GMPCyclic GMPEndothelin-1Enzyme InhibitorsGuanylate CyclaseMyosin Light ChainsNitric Oxide DonorsNitroprussideOxadiazolesQuinoxalinesTriazenesaqueous humorconventional outflowglaucomaSchlemm's canal

Identifiers

PMID24374036
PMCPMC3943640
OpenAlexW2065004555

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.