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G. Wu, P. Horner, D. Calkins; Morphometric Comparison of Age- and IOP-Dependent Changes in the Proximal and Distal Optic Nerve of the DBA/2J Mouse. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3664.
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Loss of retinal ganglion cell axons in the optic nerve of the DBA2J mouse model of pigmentary glaucoma correlates with age-dependent increases in intraocular pressure (IOP) that are due to closure of the iridocorneal angle. Here we compared quantitatively how changes in optic nerve size and axon density depend on age, IOP and location along the nerve.
We obtained optic nerve samples from 45 eyes of perfused DBA2J mice ranging from 1-13 months of age whose IOPs had been measured monthly using corneal applanation of the Tono-Pen XL. These samples were embedded in Epon resin and cross-sectioned at 1-2 um intervals both proximal to the nerve head and more distally at the optic chiasm. We used an automated microscopy system to measure nerve area in the cross-sections and to obtain complete high-magnification montages with frame-by-frame measurements of axon density and distribution.
Cross-sectional area of the nerve was highly correlated with age for both proximal (r =.94, p<<.001) and distal (r = .79, p = .06) sites, with mean area of distal nerve 1.3-1.4x larger across ages. Nerve area increased with IOP both near the eye (r = .43, p=0.01) and at the chiasm (p = 0.01), but the correlation and the rate of increase were both 1.5-2x higher at the chiasm. With increasing nerve area, axon density decreased for both proximal (r = -.44, p = .003) and distal (r = -.53, p = .006) sites, but the rate of axon loss at the chiasm was 2.6x higher across ages. Least-squares regression and covariance analysis using these combined data indicated a 1.6x greater rate of decline in axon density at the chiasm with increasing IOP than at the nerve head (p<.01).
The DBA2J optic nerve expands in breadth with age and IOP both near the eye and chiasm. As the cross-sectional area of the nerve increases, axon density is reduced, but with greater decline distal to the eye. These data support the idea that axon loss in the DBA2J involves retrograde processes.
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