Evidence map›Paper›PMID 36470430›Full record

ArticleExperimental eye research2023

The TGM2 inhibitor cysteamine hydrochloride does not impact corneal epithelial and stromal wound healing in vitro and in vivo.

A L Minella, M I Casanova, T J Chokshi, J Kang, K Cosert, M M Gragg, M A Bowman, M E Mccorkell, N L Daley, B C Leonard and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental eye research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Squishy matters - Corneal mechanobiology in health and disease.Progress in retinal and eye research · 2024
    Review
  3. Review
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

13 authors at 2 institutions in 1 country.

A L MinellaDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
M I CasanovaDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
T J ChokshiDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
J KangDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
K CosertDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
M M GraggDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
M A BowmanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
M E MccorkellDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
N L DaleyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
B C LeonardDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
C J MurphyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA; Department of Ophthalmology and Vision Science, School of Medicine, University of California, Davis, Davis, CA, USA.
V K RaghunathanDepartment of Basic Sciences, College of Optometry, University of Houston, Houston, TX, USA.
S M ThomasyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA; Department of Ophthalmology and Vision Science, School of Medicine, University of California, Davis, Davis, CA, USA. Electronic address: smthomasy@ucdavis.edu.
University of California, Davis · USUniversity of Houston · US

Funding

VISION RESEARCH CORE GRANTP30EY012576 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI MARIE E BURNS · 1999 to 2026
$18.9M
Modulation of Signal Transduction by Nano-TopographyR01EY016134 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI MURPHY, CHRISTOPHER JOHN, THOMASY, SARA MICHELLE · 2006 to 2023
$5.1M
Biophysical Cues and Corneal Wound HealingR01EY019970 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MURPHY, CHRISTOPHER JOHN · 2011 to 2020
$3.5M
Modulation of Hsp90 signaling to limit corneal fibrosis and improve ocular drug penetrationK08EY028199 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEONARD, BRIAN C. · 2017 to 2021
$1.1M
NEI NIH HHS K08 EY028199NEI NIH HHS P30 EY012576NEI NIH HHS R01 EY016134NEI NIH HHS R01 EY019970
6 · The paper itself

Abstract

Corneal wound healing is integral for resolution of corneal disease or for post-operative healing. However, corneal scarring that may occur secondary to this process can significantly impair vision. Tissue transglutaminase 2 (TGM2) inhibition has shown promising antifibrotic effects and thus holds promise to prevent or treat corneal scarring. The commercially available ocular solution for treatment of ocular manifestations of Cystinosis, Cystaran®, contains the TGM2 inhibitor cysteamine hydrochloride (CH). The purpose of this study is to assess the safety of CH on corneal epithelial and stromal wounds, its effects on corneal wound healing, and its efficacy against corneal scarring following wounding. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were first used to quantify and localize TGM2 expression in the cornea. Subsequently, (i) the in vitro effects of CH at 0.163, 1.63, and 16.3 mM on corneal epithelial cell migration was assessed with an epithelial cell migration assay, and (ii) the in vivo effects of application of 1.63 mM CH on epithelial and stromal wounds was assessed in a rabbit model with ophthalmic examinations, inflammation scoring, color and fluorescein imaging, optical coherence tomography (OCT), and confocal biomicroscopy. Post-mortem assessment of corneal tissue post-stromal wounding included biomechanical characterization (atomic force microscopy (AFM)), histology (H&E staining), and determining incidence of myofibroblasts (immunostaining against α-SMA) in wounded corneal tissue. TGM2 expression was highest in corneal epithelial cells. Application of the TGM2 inhibitor CH did not affect in vitro epithelial cell migration at the two lower concentrations tested. At 16.3 mM, decreased cell migration was observed. In vivo application of CH at 57 mM was well tolerated and did not adversely affect wound healing. No difference in corneal scarring was found between CH treated and vehicle control eyes. This study shows that the TGM2 inhibitor CH, at the FDA-approved dose, is well tolerated in a rabbit model of corneal wound healing and does not adversely affect epithelial or stromal wound healing. This supports the safe use of this medication in Cystinosis patients with open corneal wounds. CH did not have an effect on corneal scarring in this study, suggesting that Cystaran® administration to patients with corneal wounds is unlikely to decrease corneal fibrosis.

Indexed as

Corneal InjuriesCysteamineCystinosisEpithelium, CornealAnimalsCicatrixCorneaCorneal DiseasesProtein Glutamine gamma Glutamyltransferase 2RabbitsWound HealingCysteamineProtein Glutamine gamma Glutamyltransferase 2Corneal wound healingCystaranCysteamine hydrochlorideFibrosisPhototherapeutic keratectomyScarringTissue transglutaminase 2

Identifiers

PMID36470430
PMCPMC10120528
OpenAlexW4311777043

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.