Knockout of tissue transglutaminase ameliorates TGFβ2-induced ocular hypertension: A novel therapeutic target for glaucoma?

Urmimala Raychaudhuri, John Cameron Millar, Abbot Clark

Research output: Contribution to journalArticle

Abstract

Glaucoma is a vision threatening optic neuropathy that affects millions of people worldwide. In primary open angle, increased intraocular pressure (IOP) is the main risk factor for the development of this disease. Studies investigating the causes and mechanisms of increased IOP show fibrotic changes in the trabecular meshwork (TM) that are different from those of age-matched controls. Tissue transglutaminase (TGM2), an extracellular matrix (ECM) crosslinking enzyme, covalently crosslinks ECM proteins and causes excessive ECM protein deposition in the TM that could cause increased IOP. Previous literature reports increased expression of TGM2 in glaucomatous eyes compared to controls. We recently have shown that overexpression of TGM2 causes increased ECM crosslinking in the TM, increases IOP, and decreases aqueous humor (AH) outflow facility in mouse eyes. Therefore, we wanted to study the effect of TGM2 knockout (KO) on IOP in TGM2 floxed mice. Ad5.Cre transduction caused partial KO of TGM2, which decreased TGM2 expression in the TM region of mouse eyes. TGM2 KO significantly decreased IOP by itself and also in TGFβ2 induced ocular hypertensive mice. TGM2 KO also restores the outflow facility in TGFβ2 transduced eyes. Overall, TGM2 KO rescued the TGFβ2-induced ocular hypertensive phenotype. Thus, TGM2 may offer potential as a new therapeutic target for glaucoma.

Original languageEnglish
Pages (from-to)106-110
Number of pages5
JournalExperimental Eye Research
Volume171
DOIs
StatePublished - 1 Jun 2018

Fingerprint

Ocular Hypertension
Intraocular Pressure
Glaucoma
Trabecular Meshwork
Extracellular Matrix Proteins
Extracellular Matrix
Therapeutics
Optic Nerve Diseases
Aqueous Humor
transglutaminase 2
Phenotype
Enzymes

Keywords

  • Extracellular matrix (ECM)
  • Glaucoma
  • Intraocular pressure (IOP)
  • Knockout
  • Mouse
  • Tissue transglutaminase (TGM2)

Cite this

@article{3dd91e88c2d54bc2a73f69d854b1d616,
title = "Knockout of tissue transglutaminase ameliorates TGFβ2-induced ocular hypertension: A novel therapeutic target for glaucoma?",
abstract = "Glaucoma is a vision threatening optic neuropathy that affects millions of people worldwide. In primary open angle, increased intraocular pressure (IOP) is the main risk factor for the development of this disease. Studies investigating the causes and mechanisms of increased IOP show fibrotic changes in the trabecular meshwork (TM) that are different from those of age-matched controls. Tissue transglutaminase (TGM2), an extracellular matrix (ECM) crosslinking enzyme, covalently crosslinks ECM proteins and causes excessive ECM protein deposition in the TM that could cause increased IOP. Previous literature reports increased expression of TGM2 in glaucomatous eyes compared to controls. We recently have shown that overexpression of TGM2 causes increased ECM crosslinking in the TM, increases IOP, and decreases aqueous humor (AH) outflow facility in mouse eyes. Therefore, we wanted to study the effect of TGM2 knockout (KO) on IOP in TGM2 floxed mice. Ad5.Cre transduction caused partial KO of TGM2, which decreased TGM2 expression in the TM region of mouse eyes. TGM2 KO significantly decreased IOP by itself and also in TGFβ2 induced ocular hypertensive mice. TGM2 KO also restores the outflow facility in TGFβ2 transduced eyes. Overall, TGM2 KO rescued the TGFβ2-induced ocular hypertensive phenotype. Thus, TGM2 may offer potential as a new therapeutic target for glaucoma.",
keywords = "Extracellular matrix (ECM), Glaucoma, Intraocular pressure (IOP), Knockout, Mouse, Tissue transglutaminase (TGM2)",
author = "Urmimala Raychaudhuri and Millar, {John Cameron} and Abbot Clark",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.exer.2018.03.009",
language = "English",
volume = "171",
pages = "106--110",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Knockout of tissue transglutaminase ameliorates TGFβ2-induced ocular hypertension

T2 - A novel therapeutic target for glaucoma?

AU - Raychaudhuri, Urmimala

AU - Millar, John Cameron

AU - Clark, Abbot

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Glaucoma is a vision threatening optic neuropathy that affects millions of people worldwide. In primary open angle, increased intraocular pressure (IOP) is the main risk factor for the development of this disease. Studies investigating the causes and mechanisms of increased IOP show fibrotic changes in the trabecular meshwork (TM) that are different from those of age-matched controls. Tissue transglutaminase (TGM2), an extracellular matrix (ECM) crosslinking enzyme, covalently crosslinks ECM proteins and causes excessive ECM protein deposition in the TM that could cause increased IOP. Previous literature reports increased expression of TGM2 in glaucomatous eyes compared to controls. We recently have shown that overexpression of TGM2 causes increased ECM crosslinking in the TM, increases IOP, and decreases aqueous humor (AH) outflow facility in mouse eyes. Therefore, we wanted to study the effect of TGM2 knockout (KO) on IOP in TGM2 floxed mice. Ad5.Cre transduction caused partial KO of TGM2, which decreased TGM2 expression in the TM region of mouse eyes. TGM2 KO significantly decreased IOP by itself and also in TGFβ2 induced ocular hypertensive mice. TGM2 KO also restores the outflow facility in TGFβ2 transduced eyes. Overall, TGM2 KO rescued the TGFβ2-induced ocular hypertensive phenotype. Thus, TGM2 may offer potential as a new therapeutic target for glaucoma.

AB - Glaucoma is a vision threatening optic neuropathy that affects millions of people worldwide. In primary open angle, increased intraocular pressure (IOP) is the main risk factor for the development of this disease. Studies investigating the causes and mechanisms of increased IOP show fibrotic changes in the trabecular meshwork (TM) that are different from those of age-matched controls. Tissue transglutaminase (TGM2), an extracellular matrix (ECM) crosslinking enzyme, covalently crosslinks ECM proteins and causes excessive ECM protein deposition in the TM that could cause increased IOP. Previous literature reports increased expression of TGM2 in glaucomatous eyes compared to controls. We recently have shown that overexpression of TGM2 causes increased ECM crosslinking in the TM, increases IOP, and decreases aqueous humor (AH) outflow facility in mouse eyes. Therefore, we wanted to study the effect of TGM2 knockout (KO) on IOP in TGM2 floxed mice. Ad5.Cre transduction caused partial KO of TGM2, which decreased TGM2 expression in the TM region of mouse eyes. TGM2 KO significantly decreased IOP by itself and also in TGFβ2 induced ocular hypertensive mice. TGM2 KO also restores the outflow facility in TGFβ2 transduced eyes. Overall, TGM2 KO rescued the TGFβ2-induced ocular hypertensive phenotype. Thus, TGM2 may offer potential as a new therapeutic target for glaucoma.

KW - Extracellular matrix (ECM)

KW - Glaucoma

KW - Intraocular pressure (IOP)

KW - Knockout

KW - Mouse

KW - Tissue transglutaminase (TGM2)

UR - http://www.scopus.com/inward/record.url?scp=85044159136&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2018.03.009

DO - 10.1016/j.exer.2018.03.009

M3 - Article

C2 - 29535003

AN - SCOPUS:85044159136

VL - 171

SP - 106

EP - 110

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

ER -