Evidence map›Paper›PMID 25639201›Full record

ArticleExperimental eye research2015

Wnt inhibition induces persistent increases in intrinsic stiffness of human trabecular meshwork cells.

Joshua T Morgan, Vijay Krishna Raghunathan, Yow-Ren Chang, Christopher J Murphy, Paul Russell

Open access · greenAbstract read
In one paragraph

Article in Experimental eye research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 56 citations in OpenAlex.

  1. Novel Role for CGRP in Aqueous Humor Outflow.Investigative ophthalmology & visual science · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Mechanobiology in the eye.npj biological physics and mechanics · 2025
    Review
  6. Review
  7. Article
  8. GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.Investigative ophthalmology & visual science · 2024
    Article
  9. Article
  10. Squishy matters - Corneal mechanobiology in health and disease.Progress in retinal and eye research · 2024
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Normal and glaucomatous outflow regulation.Progress in retinal and eye research · 2021
    Review
  17. Article
  18. Review
  19. Cannabidiol and the Canonical WNT/β-Catenin Pathway in Glaucoma.International journal of molecular sciences · 2021
    Review
  20. Article
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

5 authors at 1 institution in 1 country.

Joshua T MorganDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, United States.
Vijay Krishna RaghunathanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, United States.
Yow-Ren ChangDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, United States.
Christopher J MurphyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, United States; Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, United States.
Paul RussellDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, United States. Electronic address: prussell@ucdavis.edu.
University of California, Davis · US

Funding

VISION RESEARCH CORE GRANTP30EY012576 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI LISA M OAKES · 1999 to 2026
$18.9M
Biophysical Cues and Corneal Wound HealingR01EY019970 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MURPHY, CHRISTOPHER JOHN · 2011 to 2020
$3.5M
Role of Biophysical Cues in the Pathogenesis of GlaucomaR01EY019475 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI RUSSELL, PAUL · 2010 to 2013
$1.5M
NEI NIH HHS P30 EY012576NEI NIH HHS P30EY12576NEI NIH HHS R01 EY019475NEI NIH HHS R01EY019475NEI NIH HHS R01 EY019970NEI NIH HHS R01EY019970
6 · The paper itself

Abstract

Wnt antagonism has been linked to glaucoma and intraocular pressure regulation, as has increased stiffness of human trabecular meshwork (HTM) tissue. We have shown culturing HTM cells on substrates that mimic the elevated stiffness of glaucomatous tissue leads to elevated expression of the Wnt antagonist secreted frizzled related protein 1 (SFRP1), suggesting a linkage between SFRP1 and HTM mechanobiology. In this study, we document biomechanical consequences of Wnt antagonism on HTM cells. Cells were treated with the Wnt antagonists (SFRP1, KY02111, and LGK-974) for 8 days and allowed to recover for 4 days. After recovery, intrinsic cell stiffness and activation of the Wnt pathway via β-catenin staining and blotting were assayed. Basal cell stiffness values were 3.71 ± 0.37, 4.33 ± 3.07, and 3.07 ± kPa (median ± S.D.) for cells derived from 3 donors. Cell stiffness increased after 0.25 μg/mL (4.32 ± 5.12, 8.86 ± 8.51, 4.84 ± 3.15 kPa) and 0.5 μg/mL (16.75 ± 5.59, 13.18 ± 7.99, and 8.54 ± 5.77 kPa) SFRP1 treatment. Stiffening was observed after 10 μM KY02111 (10.72 ± 5.63 and 6.57 ± 5.53 kPa) as well as LGK-974 (9.60 ± 7.41 and 11.40 ± 9.24 kPa) treatment compared with controls (3.79 ± 1.01 and 5.16 ± 2.14 kPa). Additionally, Wnt inhibition resulted in decreased β-catenin staining and increased phosphorylation at threonine 41 after recovery. In conclusion, this work demonstrates a causal relationship between Wnt inhibition and cell stiffening. Additionally, these findings suggest transient Wnt inhibition resulted in durable modulation of the mechanical phenotype of HTM cells. When placed in context with previous results, these findings provide a causal link between Wnt antagonism and cell stiffness and suggest a feedback loop contributing to glaucoma progression.

Indexed as

beta CateninCells, CulturedElasticityElastic ModulusHumansIntercellular Signaling Peptides and ProteinsMembrane ProteinsMicroscopy, Atomic ForceSecreted Frizzled-Related ProteinsSignal TransductionTrabecular MeshworkWnt ProteinsWnt Signaling Pathwaybeta CateninIntercellular Signaling Peptides and ProteinsMembrane ProteinsSecreted Frizzled-Related ProteinsSFRP1 protein, humanWnt ProteinsAtomic force microscopyCell stiffnessHuman trabecular meshworkSecreted frizzled related proteinWnt

Identifiers

PMID25639201
PMCPMC4352377
OpenAlexW2028185874

What OpenQuestion holds

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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.