Evidence map›Paper›PMID 25201985›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma.

Darryl R Overby, Enhua H Zhou, Rocio Vargas-Pinto, Ryan M Pedrigi, Rudolf Fuchshofer, Sietse T Braakman, Ritika Gupta, Kristin M Perkumas, Joseph M Sherwood, Amir Vahabikashi and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
13.7field-weighted citation impact, top 1% 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

129 citing papers in PubMed, 191 citations in OpenAlex.

  1. Article
  2. Article
  3. Novel Role for CGRP in Aqueous Humor Outflow.Investigative ophthalmology & visual science · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Targeting the Glutaminolysis Pathway in Glaucoma-Associated Fibrosis.International journal of molecular sciences · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

69 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

16 authors at 4 institutions in 3 countries.

Darryl R OverbyDepartment of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom;
Enhua H ZhouProgram in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;
Rocio Vargas-PintoDepartment of Biomedical Engineering, Northwestern University, Evanston, IL 60208;
Ryan M PedrigiDepartment of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom;
Rudolf FuchshoferInstitute of Human Anatomy and Embryology, Universität Regensburg, 93053 Regensburg, Germany;
Sietse T BraakmanDepartment of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom;
Ritika GuptaDepartment of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom;
Kristin M PerkumasDepartment of Ophthalmology, Duke University, Durham, NC 27710;
Joseph M SherwoodDepartment of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom;
Amir VahabikashiDepartment of Biomedical Engineering, Northwestern University, Evanston, IL 60208;
Quynh DangProgram in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;
Jae Hun KimProgram in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;
C Ross EthierDepartment of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332; Departments of Biomedical Engineering and Ophthalmology, Emory University, Atlanta, GA 30322;
W Daniel StamerDepartment of Ophthalmology, Duke University, Durham, NC 27710; Department of Biomedical Engineering, Duke University, Durham, NC 27710; and.
Jeffrey J FredbergProgram in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;
Mark JohnsonDepartment of Biomedical Engineering, Northwestern University, Evanston, IL 60208; Departments of Mechanical Engineering and Ophthalmology, Northwestern University, Evanston, IL 60208 m-johnson2@northwestern.edu.
Imperial College London · GBNorthwestern University · USDuke University · USUniversity of Regensburg · DE

Funding

Physics of collective cellular migration in lung health and diseaseP01HL120839 · NHLBI · HARVARD SCHOOL OF PUBLIC HEALTH · PI FREDBERG, JEFFREY J · 2014 to 2018
$12.2M
MULTIDISCIPLINARY VISUAL SCIENCES TRAINING PROGRAMT32EY007128 · NEI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SARTHY, VIJAY P · 1997 to 2009
$1.8M
How Does Aqueous Humor Cross the Inner Wall of Schlemm's Canal?R21EY018373 · NEI · TULANE UNIVERSITY OF LOUISIANA · PI OVERBY, DARRYL R · 2007 to 2008
$338k
NEI NIH HHS R01 EY 01969NEI NIH HHS R21 EY018373NEI NIH HHS T32 EY007128NHLBI NIH HHS P01 HL120839
6 · The paper itself

Abstract

Increased flow resistance is responsible for the elevated intraocular pressure characteristic of glaucoma, but the cause of this resistance increase is not known. We tested the hypothesis that altered biomechanical behavior of Schlemm's canal (SC) cells contributes to this dysfunction. We used atomic force microscopy, optical magnetic twisting cytometry, and a unique cell perfusion apparatus to examine cultured endothelial cells isolated from the inner wall of SC of healthy and glaucomatous human eyes. Here we establish the existence of a reduced tendency for pore formation in the glaucomatous SC cell--likely accounting for increased outflow resistance--that positively correlates with elevated subcortical cell stiffness, along with an enhanced sensitivity to the mechanical microenvironment including altered expression of several key genes, particularly connective tissue growth factor. Rather than being seen as a simple mechanical barrier to filtration, the endothelium of SC is seen instead as a dynamic material whose response to mechanical strain leads to pore formation and thereby modulates the resistance to aqueous humor outflow. In the glaucomatous eye, this process becomes impaired. Together, these observations support the idea of SC cell stiffness--and its biomechanical effects on pore formation--as a therapeutic target in glaucoma.

Indexed as

CytoskeletonEndothelial CellsEyeGlaucomaMicroscopy, Atomic ForceCells, CulturedHumanscell mechanicscytoskeletonmodulusprimary open-angle glaucoma

Identifiers

PMID25201985
PMCPMC4183270
OpenAlexW2047191461

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.