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B. K. Armstrong, R. M. Sappington, T. Sidorova, D. J. Calkins; Activation of Glial Cells in a Latex Bead Rat Model of High Pressure Glaucoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3282.
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Vision loss in glaucoma is associated with sensitivity to intraocular pressure (IOP) and the death of retinal ganglion cells (RGCs) and is also marked by activation of glial cells. Here we examined pressure-induced changes in glial cells of the retina and optic nerve in a new latex bead rat model of high pressure glaucoma (HPG).
In Brown Norway rats, we examined activation of glial cells in the retina and optic nerve of eyes with saline or latex bead (15um) anterior chamber injections. Tissue was harvested after two week 30-40% increase in IOP due to latex bead injection. Using immuno-labeling against glia-specific markers in whole eye sections and/or longitudinal sections of optic nerve, we examined changes in protein expression and morphology of Muller glia (glutamine synthetase), astrocytes (glial fibrillary acidic protein; GFAP), microglia (isolectin B4) and oligodendrocytes (myelin basic protein; MBP). Using light and electron microscopy, we examined changes in astrocyte and oligodendrocyte morphology as function of axon pathology in optic nerve.
Elevated IOP increased GFAP expression by astrocytes in the nerve fiber layer (NFL) of the retina, the ONH and the optic nerve. In the retina, increased GFAP was more robust in central retina than in the periphery and was accompanied by marked hypertrophy of the astrocytes. In areas of nerve with significant axon loss (30%), astrocyte processes were markedly larger, filling in gaps between axon bundles. In Muller glia, elevated IOP increased expression of glutamine synthetase, particularly in processes within the inner plexiform layer (IPL) and in endfeet of the ganglion cell layer (GCL) / NFL. Microglia in the retina appeared to migrate through the IPL and GCL with elevated IOP, but did not significantly change in the ONH or optic nerve. IOP-induced changes in myelin sheaths ranged from significant thinning of the sheath to hyper-myelination, but did not include a significant change in overall MBP expression by oligodendrocytes.
Elevations in IOP induce changes in glia of the retina and optic nerve, which accompany changes in RGC axonal function. These data suggest that glial activation accompanies increased IOP due to anterior chamber injection of latex beads.
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