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B. Lehpamer, S. Naymagon, X. Ye, C. Tang, P. Hof, T. Mittag, J. Danias; Quantitative Evaluation of CNS Neuronal Loss in Glaucomatous DBA/2 Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3663. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To quantitatively evaluate the extent of CNS neuronal loss in the DBA/2 mouse model of glaucoma and validate the use of MRI for quantifying CNS cell loss by comparing results obtained non-invasively with those obtained through stereological analysis of histological preparations.
Brains from pre-pathologic, 3 month old DBA/2 mice (n=6), similarly aged non-DBA/2 mice (n=3) and glaucomatous, 16-18 month old DBA/2 mice (n=11) were obtained. MR imaging of 3 young and 6 aged DBA/2 brains was conducted and the volumes of the superior colliculi (SC) and inferior colliculi (IC) of each specimen were calculated with software that allows for volume modeling (AmiraTM). The remaining brains were cryopreserved, sectioned and Nissl stained. Volume measurements of the SC and IC were obtained with software that uses stereological methods (StereoInvestigatorTM). The superior/inferior colliculus volume ratio (CVR) was calculated for each specimen. Collicular volumes and CVRs were compared across groups using t-tests and ANOVA with post-hoc Bonferroni comparison.
Mean CVR (±SD) determined using MR analysis was 1.229 (±0.114) for young DBA/2 mice and 0.982 (±0.228) for aged DBA/2 mice (t-test p=0.011). Mean CVR (±SD) determined using stereological analysis was 2.618 (±0.347) for young non-DBA/2 mice, 2.906 (±0.491) for young DBA/2 mice, and 1.810 (±0.275) for aged DBA/2 mice (CVRs of aged mice are significantly smaller, p<0.0001 ANOVA, post-hoc Bonferroni comparison). In addition, mean IC volume (determined stereologically) in aged mice is similar to those of animals in the other two groups (p>0.24 ANOVA).
MR imaging and stereological analysis confirm a decrease in the volume of the superior colliculi of aged/glaucomatous DBA/2 mice. The decrease in size of the SC in aged DBA/2 mice is not paralleled by a decrease in the size of the IC, suggesting that it is not part of a generalized age-related CNS process but rather specific to the glaucomatous process. These results validate MRI as a reliable, non-invasive method for detecting glaucomatous neurodegeneration in DBA/2 mice.
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