Dexamethasone-Induced Ocular Hypertension in Mice: Effects of Myocilin and Route of Administration.
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.
North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
Gaurang C
GC
Patel
North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
Tien N
TN
Phan
North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
Prabhavathi
P
Maddineni
North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
Ramesh B
RB
Kasetti
North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
J Cameron
JC
Millar
North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas. Electronic address: abe.clark@unthsc.edu.
Abbot F
AF
Clark
North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas. Electronic address: gulab.zode@unthsc.edu.
Gulab S
GS
Zode
D000758:Anesthesia; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D007267:Injections; D056965:Injections, Intraocular; D007429:Intraocular Pressure; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009798:Ocular Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D014129:Trabecular Meshwork / Q000187:drug effects / Q000473:pathology; D000099179:Myocilin
D024042:Collagen Type I; D003598:Cytoskeletal Proteins; D003907:Dexamethasone; D005136:Eye Proteins; D005353:Fibronectins; D006023:Glycoproteins; D000099179:Myocilin; C018038:dexamethasone acetate