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Julie Schaub, Elizabeth Cone-Kimball, Mary Ellen Pease, Ericka Oglesby, Cathy Nguyen, Harry A Quigley; Lack of regional axon loss in a murine glaucoma model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2554.
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© ARVO (1962-2015); The Authors (2016-present)
To determine if retinal ganglion cell (RGC) axon loss in experimental mouse glaucoma is uniform in the optic nerve.
Experimental glaucoma was induced for six weeks with the microbead injection model (Cone et. al. 2012) in CD1 (N=80) and C57BL/6J (B6, N=90) mice. From epoxy-embedded sections of optic nerve 1 mm posterior to the globe, axon density was calculated in 4 nerve regions: superior, inferior, nasal, and temporal.
CD1 mice normally have more RGC axons than B6, indicated by higher control axon density in every region (Table 1). The 4 regions of the optic nerve had no significant differences in axon density by pairwise comparisons in either CD1 or B6 control mouse nerves (all p>0.8, mixed model, Bonferroni corrected). As previously reported (Cone et. al. 2012), mean total axon loss in experimental glaucoma in CD1 mice was greater than in B6 mice, despite higher mean intraocular pressure (IOP) elevation in B6. Axon density loss with glaucoma was not significantly different by region in either mouse strain (all p>0.6, Table 1).
In human glaucoma, selective axon loss in the superior and inferior optic nerve is associated with lower connective tissue density and greater strain with pressure elevation in the corresponding regions of the lamina cribrosa (Quigley and Addicks 1981). The mouse lamina consists of astrocytes whose general configuration is similar to the human, but without connective tissue and without regional structure differences. While mouse lamina strain is greater nasal—temporally than superior—inferiorly, this is not associated with regionally greater axon loss. Interspecies differences in RGC injury may provide important clues in glaucoma pathogenesis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Table 1. Control and Glaucoma Regional Nerve Fiber Density
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