Evidence map›Paper›PMID 33925820›Full record

ArticleInternational journal of molecular sciences2021

The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment.

Wioletta Rozpędek-Kamińska, Grzegorz Galita, Natalia Siwecka, Steven L Carroll, John Alan Diehl, Ewa Kucharska, Dariusz Pytel, Ireneusz Majsterek

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. 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

8 authors at 3 institutions in 2 countries.

Wioletta Rozpędek-KamińskaDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland.ORCID 0000-0001-9206-1203
Grzegorz GalitaDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland.
Natalia SiweckaDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland.ORCID 0000-0002-0308-580X
Steven L CarrollDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
John Alan DiehlHollings Cancer Center, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Ewa KucharskaDepartment of Gerontology, Geriatrics and Social Work, Jesuit University Ignatianum, 31-501 Krakow, Poland.
Dariusz PytelDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland.
Ireneusz MajsterekDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland.
Medical University of Lodz · PLMedical University of South Carolina · USAkademia Ignatianum w Krakowie · PL

Funding

TRANSLATIONAL CONTROL IN ADAPTATION TO HYPOXIAP01CA104838 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SIMON, M. CELESTE · 2004 to 2018
$17.6M
UPR, interferon signaling and tumorigenesisP01CA165997 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DIEHL, JOHN ALAN · 2013 to 2023
$10.9M
Medical University of Lodz, Poland 502-03/5-108-05/502-54-224-18Medical University of Lodz, Poland 564/5-000-00/564-20-043NCI NIH HHS P01 CA104838NCI NIH HHS P01 CA165997Polish National Science Centre 2016/21/B/NZ5/01411
6 · The paper itself

Abstract

Primary open-angle glaucoma (POAG) constitutes the most common type of glaucoma. Emerging evidence suggests that Endoplasmic Reticulum (ER) stress and the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated Unfolded Protein Response (UPR) signaling pathway play a key role in POAG pathogenesis. Thus, the main aim of the study was to evaluate the effectiveness of the PERK inhibitor LDN-0060609 in cellular model of glaucoma using primary human trabecular meshwork (HTM) cells. To evaluate the level of the ER stress marker proteins, Western blotting and TaqMan gene expression assay were used. The cytotoxicity was measured by XTT, LDH assays and Giemsa staining, whereas genotoxicity via comet assay. Changes in cell morphology were assessed by phase-contrast microscopy. Analysis of apoptosis was performed by caspase-3 assay and flow cytometry (FC), whereas cell cycle progression by FC. The results obtained have demonstrated that LDN-0060609 triggered a significant decrease of ER stress marker proteins within HTM cells with induced ER stress conditions. Moreover, LDN-0060609 effectively increased viability, reduced DNA damage, increased proliferation, restored normal morphology, reduced apoptosis and restored normal cell cycle distribution of HTM cells with induced ER stress conditions. Thereby, PERK inhibitors, such as LDN-0060609, may provide an innovative, ground-breaking treatment strategy against POAG.

Indexed as

Glaucoma, Open-AngleApoptosisCell LineCell ProliferationDNA DamageeIF-2 KinaseEndoplasmic Reticulum StressEukaryotic Initiation Factor-2HumansProtein Kinase InhibitorsUnfolded Protein ResponseeIF-2 KinaseEukaryotic Initiation Factor-2Protein Kinase InhibitorsapoptosiseIF2αendoplasmic reticulum stressglaucomaglaucoma treatmentPERKPERK inhibitorunfolded protein response

Identifiers

PMID33925820
PMCPMC8123501
OpenAlexW3159036886

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.