TY - JOUR
T1 - Dexamethasone-Induced Ocular Hypertension in Mice
T2 - Effects of Myocilin and Route of Administration
AU - Patel, Gaurang C.
AU - Phan, Tien N.
AU - Maddineni, Prabhavathi
AU - Kasetti, Ramesh B.
AU - Millar, J. Cameron
AU - Clark, Abbot F.
AU - Zode, Gulab S.
N1 - Funding Information:
Supported by National Eye Institute grants R01EY016242 (A.F.C.), EY022077 (G.S.Z.), and EY026177 (G.S.Z.).
Publisher Copyright:
© 2017 American Society for Investigative Pathology
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious adverse effect of prolonged GC therapy that can lead to iatrogenic glaucoma and permanent vision loss. An appropriate mouse model can help us understand precise molecular mechanisms and etiology of GC-induced OHT. We therefore developed a novel, simple, and reproducible mouse model of GC-induced OHT. GC-induced myocilin expression in the trabecular meshwork (TM) has been suggested to play an important role in GC-induced OHT. We further determined whether myocilin contributes to GC-OHT. C57BL/6J mice received weekly periocular conjunctival fornix injections of a dexamethasone-21-acetate (DEX-Ac) formulation. Intraocular pressure (IOP) elevation was relatively rapid and significant, and correlated with reduced conventional outflow facility. Nighttime IOPs were higher in ocular hypertensive eyes compared to daytime IOPs. DEX-Ac treatment led to increased expression of fibronectin, collagen I, and α-smooth muscle actin in the TM in mouse eyes. No changes in body weight indicated no systemic toxicity associated with DEX-Ac treatment. Wild-type mice showed increased myocilin expression in the TM on DEX-Ac treatment. Both wild-type and Myoc−/− mice had equivalent and significantly elevated IOP with DEX-Ac treatment every week. In conclusion, our mouse model mimics many aspects of GC-induced OHT in humans, and we further demonstrate that myocilin does not play a major role in DEX-induced OHT in mice.
AB - Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious adverse effect of prolonged GC therapy that can lead to iatrogenic glaucoma and permanent vision loss. An appropriate mouse model can help us understand precise molecular mechanisms and etiology of GC-induced OHT. We therefore developed a novel, simple, and reproducible mouse model of GC-induced OHT. GC-induced myocilin expression in the trabecular meshwork (TM) has been suggested to play an important role in GC-induced OHT. We further determined whether myocilin contributes to GC-OHT. C57BL/6J mice received weekly periocular conjunctival fornix injections of a dexamethasone-21-acetate (DEX-Ac) formulation. Intraocular pressure (IOP) elevation was relatively rapid and significant, and correlated with reduced conventional outflow facility. Nighttime IOPs were higher in ocular hypertensive eyes compared to daytime IOPs. DEX-Ac treatment led to increased expression of fibronectin, collagen I, and α-smooth muscle actin in the TM in mouse eyes. No changes in body weight indicated no systemic toxicity associated with DEX-Ac treatment. Wild-type mice showed increased myocilin expression in the TM on DEX-Ac treatment. Both wild-type and Myoc−/− mice had equivalent and significantly elevated IOP with DEX-Ac treatment every week. In conclusion, our mouse model mimics many aspects of GC-induced OHT in humans, and we further demonstrate that myocilin does not play a major role in DEX-induced OHT in mice.
UR - http://www.scopus.com/inward/record.url?scp=85016054020&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2016.12.003
DO - 10.1016/j.ajpath.2016.12.003
M3 - Article
C2 - 28167045
AN - SCOPUS:85016054020
SN - 0002-9440
VL - 187
SP - 713
EP - 723
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -