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F. E. Cone, S. E. Gelman, J. L. Son, M. E. Pease, H. A. Quigley; Differential Susceptibility to Experimental Glaucoma Among 3 Mouse Strains: A New Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6389.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a new, inducible mouse glaucoma model and to test the susceptibility to retinal ganglion cell (RGC) and axon loss among 3 mouse strains and comparing young and old mice.
We obstructed the mouse aqueous outflow channels with polystyrene beads and viscoelastic injection into the anterior chamber, evaluating the effects by intraocular pressure (IOP) measurement, light and confocal microscopy, and both RGC body and axon quantitative counting in whole mounts labeled by DAPI and cross-sections of epoxy-embedded optic nerve. Three strains of mice were compared: young mice (2 months): C57/BL6, DBA/2J, and CD1, and older (10 month) C57/BL6 mice.
The injection through a glass micropipette of 2 µL of concentrated, 6 µm beads followed by 3 µL of viscoelastic produced more consistent and prolonged IOP elevation than 1, 3, or 15 µm beads. IOP rose at ≥1 time point in 94.1% of eyes (112/119), with mean IOP difference from uninjected fellow eyes of 4.4 + 3.0 mm Hg. Histologically, beads blocked both trabecular and uveoscleral outflow pathways. By 6-12 weeks, injected eyes were 10.8% longer and 7.6% wider (both p < 0.0001), with elongation significantly greater than widening (p = 0.0009). Young DBA/2J and C57/BL6 eyes increased axial length significantly more than young CD1 or old C57/BL6 (all p ≤ 0.01). CD1 mice lost significantly more RGC layer cells and optic nerve axons that the other 3 groups (p from 0.04 to <0.0001), even when accounting for differences in measured IOP exposure. Young C57/BL6 eyes elongated more and lost more RGC layer cells and axons than older C57/BL6 mice (p=0.02 and 0.01, respectively). Injury in the retina was limited to the RGC layer.
A practical, consistent and inexpensive mouse model for induced, chronic IOP elevation used bead/viscoelastic injection. There was differential susceptibility to fixed ocular elongation and RGC loss among 3 mouse strains and by age. Factors that determine sensitivity to RGC injury can now be studied more easily using transgenic mouse strains.
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