Evidence map›Paper›PMID 39087933›Full record

ArticleInvestigative ophthalmology & visual science2024

GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.

Chenna Kesavulu Sugali, Naga Pradeep Rayana, Jiannong Dai, Devon H Harvey, Kamesh Dhamodaran, Weiming Mao

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

6 authors.

Chenna Kesavulu SugaliEugene & Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States.
Naga Pradeep RayanaEugene & Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States.
Jiannong DaiEugene & Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States.
Devon H HarveyEugene & Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States.
Kamesh DhamodaranEugene & Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States.
Weiming MaoEugene & Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States.

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
The role of Wnt signaling in treating glucocorticoid-induced glaucomaR01EY031700 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI MAO, WEIMING · 2021 to 2025
$2.5M
Cross-talk between TGF-beta and Wnt pathways in the trabecular meshworkR01EY026962 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI MAO, WEIMING · 2017 to 2021
$1.9M
The role of distal aqueous humor outflow tissue in glucocorticoid-induced glaucomaR21EY033929 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI MAO, WEIMING · 2023 to 2024
$436k
Identification of genes responsible for glucocorticoid-induced glaucomaR21EY023048 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI MAO, WEIMING · 2013 to 2014
$388k
NCATS NIH HHS UL1 TR002529NEI NIH HHS R01 EY026962NEI NIH HHS R01 EY031700NEI NIH HHS R21 EY023048NEI NIH HHS R21 EY033929
6 · The paper itself

Abstract

Purpose: Primary open-angle glaucoma (POAG) is a leading cause of blindness, and its primary risk factor is elevated intraocular pressure (IOP) due to pathologic changes in the trabecular meshwork (TM). We previously showed that there is a cross-inhibition between TGFβ and Wnt signaling pathways in the TM. In this study, we determined if activation of the Wnt signaling pathway using small-molecule Wnt activators can inhibit TGFβ2-induced TM changes and ocular hypertension (OHT). Methods: Primary human TM (pHTM) cells and transduced SBE-GTM3 cells were treated with or without Wnt and/or TGFβ signaling activators and used for luciferase assays; for the extraction of whole-cell lysate, conditioned medium, cytosolic proteins, and nuclear proteins for Western immunoblotting (WB); or for immunofluorescent staining. Human donor eyes were perfusion cultured to study the effect of Wnt activators on IOP. Results: We found that the small-molecule Wnt activators (GSK3β inhibitors) (BIO, SB216763, and CHIR99021) activated canonical Wnt signaling in pHTM cells without toxicity at tested concentrations. This activation inhibited TGFβ signaling as well as TGFβ2-induced extracellular matrix deposition and formation of cross-linked actin networks in pHTM cells or SBE-GTM3 cells. We also observed nuclear translocation of both Smad4 and β-catenin in pHTM cells, which suggested that the cross-inhibition between the TGFβ and Wnt signaling pathways may occur in the nucleus. Using our ex vivo model, we found that CHIR99021 inhibited TGFβ2-induced OHT in perfusion-cultured human eyes. Conclusions: Our results showed that small-molecule Wnt activators have the potential for treating TGFβ signaling-induced OHT in patients with POAG.

Indexed as

Glaucoma, Open-AngleGlycogen Synthase Kinase 3 betaIntraocular PressureTrabecular MeshworkBlotting, WesternCells, CulturedHumansOcular HypertensionSignal TransductionTransforming Growth Factor betaTransforming Growth Factor beta2Wnt Signaling PathwayGlycogen Synthase Kinase 3 betaTransforming Growth Factor betaTransforming Growth Factor beta2

Identifiers

PMID39087933
PMCPMC11305430

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Registered trials

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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.