Abstract
Purpose: :
Retinal ganglion cell axonal degeneration in the optic nerve of the DBA2J mouse model of pigmentary glaucoma depends on age-related increases in intraocular pressure (IOP) due to closure of the iridocorneal angle. Here we compared quantitatively changes in glial cell populations with age-dependent changes in optic nerve size and axon density.
Methods: :
We obtained optic nerve samples from 50 eyes of perfused DBA2J mice ranging from 1-13 months of age that had undergone IOP measurement using Tono-Pen XL applanation. Samples of nerve proximal to the globe were embedded in Epon resin, cross-sectioned at 0.8-1.5 um intervals, counter-stained and examined quantitatively by an automated microscopy system with frame-by-frame measurements of axon density and distribution. Glial populations were quantified in these same samples using morphological discrimination and electron microscopy. Other portions of nerve were prepared for immunocytochemical labeling.
Results: :
With age, cross-sectional area of the optic nerve increased (r =.94, p<.01); dependence on IOP also increased with age and was greatest between 5-9 months. Nerve area did not change with age in C57 mice. With increasing nerve area in the DBA2J, the number of degenerating axonal profiles increased significantly (r = 0.69, p <.05) and was correlated with increasing numbers of both oligodendrocyte and astrocyte glia in the nerve. Though total numbers of both glia types increased moderately with nerve area, their density (number per unit area) actually decreased as the nerve expanded with age (r=-0.61, p < .05). Levels of myelin basic protein were unchanged.
Conclusions: :
With age, the number of oligodendrocyte and astrocyte glia in the DBA2J optic nerve increase moderately with breadth of optic nerve and numbers of degenerating axon profiles, though the rate of nerve expansion is greater. That myelin basic protein remains unchanged with loss of axons in the nerve is likely indicative of the increase in oligodendrocyte number and increased incidence of multiple myelin sheaths.
Keywords: optic nerve • oligodendrocyte • glia