Evidence map›Paper›PMID 25395486›Full record

ArticleInvestigative ophthalmology & visual science2014

Shear stress-triggered nitric oxide release from Schlemm's canal cells.

Nicole E Ashpole, Darryl R Overby, C Ross Ethier, W Daniel Stamer

Open access · greenAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Loss of cerebral autoregulation drives abnormal perfusion patterns after stroke.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  9. Article
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  11. Article
  12. Article
  13. The Factors Affecting the Stability of IOP Homeostasis.Investigative ophthalmology & visual science · 2024
    Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. YAP/TAZ Mediate TGFβ2-Induced Schlemm's Canal Cell Dysfunction.Investigative ophthalmology & visual science · 2022
    Article
  20. Article

1 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

4 authors at 2 institutions in 2 countries.

Nicole E AshpoleBiomedical Engineering, Duke University, Durham, North Carolina, United States.
Darryl R OverbyDepartment of Bioengineering, Imperial College London, London, United Kingdom.
C Ross EthierDepartment of Bioengineering, Imperial College London, London, United Kingdom Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States.
W Daniel StamerOphthalmology Department, Duke University, Durham, North Carolina, United States.
Duke University · USImperial College London · GB

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
eNOS-Dependent Mechanoregulation of Intraocular PressureR01EY022359 · NEI · DUKE UNIVERSITY · PI STAMER, W DANIEL · 2012 to 2025
$5.6M
NEI NIH HHS EY005722NEI NIH HHS EY022359NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY022359
6 · The paper itself

Abstract

purposeEndothelial nitric oxide (NO) synthase is regulated by shear stress. At elevated intraocular pressures when the Schlemm's canal (SC) begins to collapse, shear stress is comparable with that in large arteries. We investigated the relationship between NO production and shear stress in cultured human SC cells.

methodsSchlemm's canal endothelial cells isolated from three normal and two glaucomatous human donors were seeded into Ibidi flow chambers at confluence, cultured for 7 days, and subjected to steady shear stress (0.1 or 10 dynes/cm(2)) for 6, 24, or 168 hours. Cell alignment with flow direction was monitored, and NO production was measured using 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) and Griess reagents. Human trabecular meshwork (TM) and umbilical vein endothelial cells (HUVECs) were used as controls.

resultsNormal SC strains aligned with the direction of flow by 7 days. Comparing 0.1 vs. 10 dynes/cm(2), NO levels increased by 82% at 24 hours and 8-fold after 7 days by DAF-FM, and similar results were obtained with Griess reagent. Shear responses by SC cells at 24 hours were comparable with HUVECs, and greater than TM cells, which appeared shear-insensitive. Nitric oxide production by SC cells was detectable as early as 6 hours and was inhibited by 100 μM nitro-L-arginine methyl ester. Two glaucomatous SC cell strains were either unresponsive or lifted from the plate in the face of shear.

conclusionsShear stress triggers NO production in human SC cells, similar to other vascular endothelia. Increased shear stress and NO production during SC collapse at elevated intraocular pressures may in part mediate IOP homeostasis.

Indexed as

Stress, MechanicalAgedAged, 80 and overAnalysis of VarianceAqueous HumorCase-Control StudiesCells, CulturedEndothelial CellsFemaleGlaucomaHumansHuman Umbilical Vein Endothelial CellsIntraocular PressureMaleMiddle AgedNitric OxideNitric OxideNitric Oxide Synthaseaqueous humorconventional outfloweNOSglaucomaintraocular pressure

Identifiers

PMID25395486
PMCPMC4266075
OpenAlexW2027140863

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.