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A. Whitlock, B. McKnight, D. S. Rice; Increased Intraocular Pressure in Mice Treated With Dexamethasone. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2100.
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The mouse continues to gain popularity as a model species for glaucoma research because of anatomical and physiological similarities (with respect to aqueous humor dynamics) between mice and primates, and the increased availability of genetically modified mice. Advances in techniques to monitor intraocular pressure (IOP) in mice have facilitated longitudinal measurementsof this important risk factor associated with glaucoma. The purpose of this study was to investigate the IOP effect of systemic delivery of dexamethasone in normotensive mice.
Osmotic mini-pumps delivering dexamethasone were implanted into male hybrid mice (C57BL/6J-Tyrc-Brd x 129S5/SvEvBrd, F2 generation). A separate cohort (controls) received PBS-filled pumps. IOP was recorded using a TonoLab tonometer on both groups of mice under isoflurane anesthesia before (baseline) and after pump implantation, for a period of 28 days. Serum samples were collected for pharmacokinetic (PK) analyses, and eyes were harvested for histology. Pharmacological responses were observed between days 21 and 25, following topical administration of ocular hypotensive agents.
Continuous administration of dexamethasone resulted in a significant increase of 3.4 ± 0.4 mm Hg (mean ± SEM) in IOP when compared with baseline IOP measurements. This increase in IOP peaked at 21 days and remained constant. No significant change in IOP was observed in the PBS-treated mice. Plasma levels of dexamethasone were 238 ± 37 nM (mean ± SEM) at 7 days post-implant, and 78 ± 18 nM (mean ± SEM) on day 28. There was no correlation on day 28 between the magnitude of IOP increase and plasma dexamethasone levels. No obvious obstructions in the outflow pathway were observed histologically. Mice with dexamethasone-induced increases in IOP were more responsive to timolol, latanoprost, and Y-39983 compared to PBS-control mice.
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