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Tien Phan, Ramesh Kasetti, Amit Sope, J Cameron Millar, Abbot F Clark, Gulab Zode; Periocular injections of dexamethasone reduce outflow facility and elevate intraocular pressure in C57 mice.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6450.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular hypertension is a serious side effect of glucocorticoid therapy. We have previously shown that thrice-daily topical ocular dexamethasone (Dex) phosphate significantly elevated IOP in normal C57 mice after 3-weeks of treatment. To further simplify this process, we sought to examine whether weekly periocular injections of various Dex formulations elevate IOP in normal C57 mice. We further explored the role of myocilin (Myoc) in Dex-induced ocular hypertension using Myoc knock out (KO) mice and transgenic mice overexpressing WT myocilin (Tg-WTMYOC).
Periocular injections of vehicle or Dex phosphate (50, 200 and 500μg) or Dex acetate (20μg) were performed in C57 mice (2 and 6 month) every week and conscious IOP was measured using rebound tonometer. Outflow facility was measured using constant flow infusion after 5-weeks of injections. To determine the role of myocilin in Dex-induced ocular hypertension, IOP was monitored in Myoc KO and WT Myoc-Tg mice injected with 200μg Dex phosphate weekly.
Periocular injections of Dex significantly elevated IOP in both 2 and 6 month-old C57 mice (p<0.0001). 1-week post injections, IOP in vehicle-treated mice was 13.96mmHg (n=6), in 20μg Dex acetate-treated mice was 16.88mmHg (n=6), in 50μg Dex phosphate mice was 16.81mmHg (n=8), in 200μg Dex phosphate-treated mice was 18.2mmHg (p<0.0001, n=8), and in 500μg Dex phosphate-treated mice was 18.3mmHg (n=4). Similar level of IOP elevation was observed in subsequent weeks of Dex treatment. Outflow facility in Dex phosphate (200μg) treated mice was significantly decreased compared to vehicle-treated mice (0.02243 μl/min/mmHg in vehicle vs 0.01425 μl/min/mmHg in Dex-treated mice, p<0.03, n=8). In addition, IOP elevation in Dex-treated Myoc KO and WT Myoc transgenic mice was similar to C57 mice treated with Dex, suggesting that loss of myocilin or overexpression of WT myocilin does not alter Dex-induced ocular hypertension.
These studies indicate that periocular injections of Dex phosphate reduce outflow facility and elevate IOP in C57 mice providing an easier model to study GC-induced ocular hypertension.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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