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Matthew Steinhart, Elizabeth Cone-Kimball, Cathy Nguyen, Thao D Nguyen, Mary Ellen Pease, Shukti Chakravarti, Ericka Oglesby, Harry Quigley, Glaucoma Center of Excellence; Age Effect on Glaucoma Susceptibility: CD1 vs B6. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3818.
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© ARVO (1962-2015); The Authors (2016-present)
To study the effects of age and strain background on susceptibility to retinal ganglion cell (RGC) axon loss in a murine experimental glaucoma model.
A chronic experimental glaucoma protocol involving microbead injection into the anterior chamber (Cone et al. Exp Eye Res, 2012) was performed on mice of two distinct ages: 2 months (younger) and 12 months (older). The animals included in this study were of two different strain backgrounds, CD1 and C57BL/6 (B6). During the 6-week experimental glaucoma protocol, intraocular pressure (IOP) was measured using a Tonolab. After sacrifice, perfusion, and enucleation, susceptibility to RGC axon loss was measured by counting optic nerve axons.
At baseline, younger mice of both strains displayed a higher mean IOP than that of older mice of their respective backgrounds: CD1 (p = 0.001, t test), B6 (p = 0.01, t test). Younger CD1 mice showed baseline mean IOP of 13.4 ± 2.3 mmHg (n = 86), and older CD1 mice showed baseline mean IOP of 11.4 ± 3.3 mmHg (n = 42). Younger B6 mice showed baseline mean IOP of 12.6 ± 2.4 mmHg (n = 92), while older B6 mice had baseline mean IOP of 11.1 ± 3.6 mmHg (n = 32). Older CD1 mice experienced significantly greater RGC axon loss due to experimental glaucoma than younger CD1 mice (p = 0.01, multivariate regression). Older CD1 mice started with a baseline mean of 61,989 RGC axons and after treatment, 41,195 RGC axons remained, representing a 33.5% axon loss. Younger CD1 mice started with a baseline mean of 61,188 RGC axons and after treatment, 49,476 RGC axons remained, representing a 19.1% axon loss. In past experiments, older B6 mice had significantly greater RGC axon loss compared to younger mice in this glaucoma model (p = 0.01, multivariate regression).
The CD1 mouse strain exhibited greater RGC axon loss in older mice, while B6 mice had the opposite tendency (less loss in older mice). Age-related effects of glaucoma may depend upon the strain or type of mice studied.
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