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J Cameron Millar, Iok-Hou Pang, Abbot F Clark; Strain Survey of Aqueous Humor Dynamics in the Mouse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2907.
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© ARVO (1962-2015); The Authors (2016-present)
Recently mice have been extensively used as an experimental model for glaucoma. The mouse eye bears many similarities to the human in terms of anatomy, physiology, and pharmacology. However, its small size presents a challenge for the study of aqueous humor dynamics (AHD). Mouse AHD parameters have been studied by several laboratories in various strains, but there is no clear consensus. We hypothesize that strain differences may play a role. This study was designed to evaluate potential differences in AHD among several commonly used mouse strains with or without ocular hypertension induced by intraocular injection of a viral vector encoding mutant myocilin.
Female BALB/cJ, A/J, and C57-BL/6J mice, aged 12-25 weeks and weighing between 21 and 28g were utilized. Animals were fed standard chow and kept in 12h light/12h dark conditions (lights on @0600hrs). Intraocular pressure (IOP) was elevated in the left eye by intravitreal injection of Ad5.MYOC.Y437H. The right (naïve) eye was not injected. IOP was measured using a TonoLab tonometer (ICare®). AHD parameters (outflow facility (C), episcleral venous pressure (Pe), aqueous humor inflow rate (Fin), and uveoscleral outflow rate (Fu)) were established by constant flow infusion in anesthetized animals following our previously published methodology (Millar et al., IOVS 52: 685-694, 2011).
Intravitreal injection of Ad5.MYOC.Y437H significantly increased IOP in BALB/cJ mice (P<0.001), A/J mice (P=0.001) and C57-BL/6J mice (P<0.001). Mean C in A/J mouse eyes was greater than that of BALB/cJ mouse eyes (1.24× (naïve); 1.21× (injected)), and mean C in C57-BL/6J mouse eyes was greater than that of BALB/cJ mouse eyes (1.52× (naïve); 1.26× (injected)). In each strain, C in eyes injected with Ad5.MYOC.Y437H was significantly reduced, by a factor of 1.32× (BALB/cJ), 1.35× (A/J) and 1.58× (C57-BL/6J) compared with uninjected contralateral eyes (P=0.00716, ANOVA). Fu and Pe were not found to be significantly different between the BALB/cJ and the A/J strains, nor between the naïve or Ad5.MYOC.Y437H-injected eyes within these strains.
There are strain differences in C but not in other AHD parameters. Intravitreal injection of a vector encoding mutant myocilin increased IOP mainly due to a reduction in C.
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