Evidence map›Paper›PMID 29097767›Full record

ArticleScientific reports2017

Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork.

Ramesh B Kasetti, Prabhavathi Maddineni, J Cameron Millar, Abbot F Clark, Gulab S Zode

Abstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing 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

63 citing papers in PubMed.

  1. Article
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  8. Proteomic analysis of liver fibrosis reveals EFEMP1 as a new modulator of focal adhesion and migration of hepatic stellate cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Mechanobiology in the eye.npj biological physics and mechanics · 2025
    Review
  14. Mouse Model of Glucocorticoid-Induced Glaucoma.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  15. Review
  16. Review
  17. Role of TGF-β1/SMADs signalling pathway in resveratrol-induced reduction of extracellular matrix deposition by dexamethasone-treated human trabecular meshwork cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024
    Article
  18. Article
  19. Article
  20. Article

3 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

5 authors.

Ramesh B KasettiThe North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, TX, 76107, Fort Worth, USA.
Prabhavathi MaddineniThe North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, TX, 76107, Fort Worth, USA.
J Cameron MillarThe North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, TX, 76107, Fort Worth, USA.
Abbot F ClarkThe North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, TX, 76107, Fort Worth, USA.
Gulab S ZodeThe North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, TX, 76107, Fort Worth, USA. gulab.zode@unthsc.edu.

Funding

Crosstalk Between Unfolded Protein Response and Autophagy for the Treatment of GlaucomaR01EY026177 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI ZODE, GULAB · 2016 to 2025
$3.8M
Targeting ER Stress Pathway Using Sodium 4-Phenylbutyrate for the Treatment of POAGR01EY028616 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI ZODE, GULAB · 2018 to 2021
$1.4M
Role of ER Stress in the Pathogenesis of Primary Open Angle GlaucomaR00EY022077 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI ZODE, GULAB · 2014 to 2016
$740k
Role of ER Stress in the Pathogenesis of Primary Open Angle GlaucomaK99EY022077 · NEI · UNIVERSITY OF IOWA · PI ZODE, GULAB · 2012 to 2013
$175k
NEI NIH HHS K99 EY022077NEI NIH HHS R00 EY022077NEI NIH HHS R01 EY026177NEI NIH HHS R01 EY028616
6 · The paper itself

Abstract

Increased synthesis and deposition of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) is associated with TM dysfunction and intraocular pressure (IOP) elevation in glaucoma. However, it is not understood how ECM accumulation leads to TM dysfunction and IOP elevation. Using a mouse model of glucocorticoid (GC)-induced glaucoma, primary human TM cells and human post-mortem TM tissues, we show that increased ECM accumulation leads to endoplasmic reticulum (ER) stress in the TM. The potent GC, dexamethasone (Dex) increased the secretory protein load of ECM proteins in the ER of TM cells, inducing ER stress. Reduction of fibronectin, a major regulator of ECM structure, prevented ER stress in Dex-treated TM cells. Overexpression of fibronectin via treatment with cellular fibronectin also induced chronic ER stress in primary human TM cells. Primary human TM cells grown on ECM derived from Dex-treated TM cells induced ER stress markers. TM cells were more prone to ER stress from ECM accumulation compared to other ocular cell types. Moreover, increased co-localization of ECM proteins with ER stress markers was observed in human post-mortem glaucomatous TM tissues. These data indicate that ER stress is associated with increased ECM accumulation in mouse and human glaucomatous TM tissues.

Indexed as

Endoplasmic Reticulum StressAnimalsCells, CulturedDisease Models, AnimalExtracellular Matrix ProteinsGlaucomaHumansMiceProtein BiosynthesisTrabecular MeshworkExtracellular Matrix Proteins

Identifiers

PMID29097767
PMCPMC5668243

What OpenQuestion holds

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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.