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Mark Vezina, Christian Li; Comparison of the Effect of Latanoprost on IOP Lowering in Two Strains of Normotensive Rat. Invest. Ophthalmol. Vis. Sci. 2014;55(13):139.
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Intraocular pressure (IOP) measurements are a common endpoint in ocular efficacy and toxicology studies. However, for rats there can be significant differences between strains in response to IOP lowering drugs. This study evaluated the effect of the IOP lowering agent latanoprost in Brown Norway and Wistar rats.
Twelve male Brown Norway and 10 male Wistar normotensive rats were subjected to bilateral IOP measurements at 4 to 6 time points/day (occasion) using a Tonovet rebound tonometer. Up to 3 baseline occasions were obtained from each strain to characterize diurnal changes. Latanoprost was administered as a single bilateral topical instillation in the morning on 3 separate occasions with a minimum 48 hours between doses. Three or 5 measurements/eye were recorded and averaged at each time point.
Latanoprost resulted in an initial elevation of IOP in both strains consistent with results described in the literature. In Brown Norway rats IOP returned to baseline or just slightly below baseline with no significant IOP reduction. Wistar rats demonstrated a subsequent mean IOP reduction of 3-5 mm Hg from the baseline range approximately 5 hours post dose.
These data demonstrated there can be significant differences in response of rat strains to IOP lowering drugs. Brown Norway rats were unresponsive to the IOP lowering effects of latanoprost, while Wistar rats showed peak lowering at 5 hours post dose of up to 5 mm Hg. The potential difference in response of rat strains to IOP lowering drugs should be considered, especially when designing early efficacy studies, to avoid misleading results.
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