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Editors Selection IGR 17-4
Basic Science: Experimental glaucoma
Comment by John Morrison on:
67161 A Magnetic Microbead Occlusion Model to Induce Ocular Hypertension-Dependent Glaucoma in Mice, Ito YA; Belforte N; Cueva Vargas JL et al., Journal of Vision Exp, 2016; 0:
Understanding mechanisms of glaucomatous optic nerve damage is essential for developing new treatments to modulate axonal injury. This relies heavily on the development of reliable animal models of chronically elevated intraocular pressure (IOP). While several models have been developed for rodents over the years, injection of microbeads in the anterior chamber has gained increased popularity, due to surgical simplicity and a greater degree of success.1,2 Samsel et al. subsequently modified this approach by injecting magnetic microspheres and directing them into the anterior chamber angle with a magnet to improve efficiency of aqueous outflow obstruction.3
While specific methods for producing this model in rats appeared in an earlier volume of this journal,4 Ito et al. present a step-by-step description of producing this model in mice. They provide important details that help overcome the specific challenges presented by these small eyes, and the accompanying video nicely details specifics that are difficult to convey in words, such as microneedle construction and the injection technique.
The authors nicely document the IOP elevation and retinal ganglion cell and axonal effects in this model. Although total axon counts were found to be significantly reduced three weeks after injection, there was no further reduction by six weeks, despite continued elevation of IOP. The authors suggest that longer durations of observation may be required. However, initial IOP responses, not documented during the first few days after injection, could also be much higher than anticipated, which could lead to this initial injury, particularly in these small, more vulnerable eyes. Additionally, while IOP's are rightly carefully documented in awake animals, this is restricted to day-time measurements. Since IOP in mice is normally elevated in the dark phase of the circadian cycle,5 outflow obstruction may result in additional, significant night-time IOP elevations. Full documentation of the complete IOP response would further strengthen the utility of this model.
References
- Sappington RM, et al. The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice. Invest Ophthalmol Vis Sci 2009;51(1):207-216.
- Cone FE, et al. Differential susceptibility to experimental glaucoma among 3 mouse strains using bead and viscoelastic injection. Exp Eye Res 2010;91(3):415-424.
- Samsel PA, et al. A novel method for the induction of experimental glaucoma using magnetic microspheres. Invest Ophthalmol Vis Sci 2011;2(3):1671-1675.
- Bunker S, et al. Experimental glaucoma induced by ocular injection of magnetic microspheres. J Vis Exp 2015;96.
- Li R, Liu JH. Telemetric monitoring of 24 h intraocular pressure in conscious and freely moving C57BL/6J and CBA/CaJ mice. Mol Vis 2008;14:745-749.
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