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
SN - 0014-4835
VL - 171
SP - 106
EP - 110
JO - Experimental Eye Research
JF - Experimental Eye Research
ER -