Abstract
Purpose: :
The DBA/2J line of mice develops glaucoma with a characteristic sectorial loss of retinal ganglion cells, pointing to the optic nerve head as the site of initial damage to their axons. The murine optic nerve head contains astrocytes of a characteristic morphological type ("catcher’s mitt" shape) that ensheath the axon bundles and form a glial lamina. Recently, we showed that the astrocytes in the optic nerve undergo biphasic remodeling after crush injury (Sun et al., 2010). In the first phase (3-7 days), they retract their processes, and reduce their spatial coverage. At a later stage (1-2 weeks) they re-extend long, thin processes, but without reestablishing the normal architecture of the glial lamina. Here we extend our findings from optic nerve crush to the slowly developing glaucoma that occurs in DBA/2J mice.
Methods: :
We backcrossed a transgenic mouse line expressing GFP in individual astrocytes (hGFAPpr-GFP) into the DBA/2J line. Mice were aged to 1-16 months. Retinas were stained with a neurofilament marker to detect ganglion cell and axon loss. Image stacks through optic nerve astrocytes were taken on a confocal microscope.
Results: :
Fifty-four retinas and optic nerves were analyzed. We did not detect signs of ganglion cell degeneration in retinas from animals <6 months old. In older animals, all stages of degeneration from mild sectorial defects to total loss of all ganglion cells were observed. Astrocytes from eyes with no signs of ganglion cell degeneration were normal. In the nerves from mildly to moderately glaucomatous retinas, we found cells with fewer, thicker primary processes, but also cells that appeared normal. In the optic nerves of severely glaucomatous retinas, the astrocytes resembled those in the second stage after nerve crush; they crossed much of the space of the optic nerve head, but had on average, shorter, thinner, and less regular processes.
Conclusions: :
Astrocytes in the glial lamina undergo rearrangement in glaucoma. Due to the slow and gradual onset of glaucoma, we do not presently know whether the astrocytes in glaucoma also go through the transient first phase of remodeling that is observed after nerve crush. The astrocytes of glial scars -either after crush or in severe glaucoma - are of the same characteristic morphology.
Keywords: astrocytes: optic nerve head • ganglion cells • microscopy: confocal/tunneling