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A. Ebneter, G. Chidlow, J. P. M. Wood, R. J. Casson; Microglial Activation in the Optic Nerve and Tract in a Rat Model of Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2762.
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Glaucoma exhibits typical features of neurodegenerative CNS disorders. Microglia and astrocytes are the main cellular elements initiating defence mechanisms against destructive influences and promoting regenerative processes; however, overactivation can also cause secondary damage. To date, little attention has been paid to the role of the glia in the optic nerve and tract and it is unclear whether glial activation is noxious or beneficial to neuronal survival. The aim of the current work was to characterize the glial response in a rat model of experimental glaucoma.
Experimental glaucoma was induced in adult Sprague-Dawley rats by lasering the trabecular meshwork using a standard protocol. Rats were saline perfused and killed at various time points between 1 to 6 weeks after the procedure. Both eyes and the optic nerves and tracts were collected and processed for immunohistochemistry using standard methodologies. Sections were analysed for markers of quiescent and activated microglia, including ED1 (CD68), Iba1, OX18 (MHC-I), OX6 (MHC-II) and OX42 (macrophage complement receptor 3). In addition, the extent of axonal injury was assessed by neurofilament staining, and the astrocytic response was monitored using nestin, alpha-B-crystallin and hsp27.
Experimental glaucoma caused marked activation of microglia in the retina, optic nerve and tract. No activation was found in the corresponding contralateral structures. The degree of activation, characterized by increased cell density and morphologic changes from the resting ramified form to the amoeboid shape, correlated with axonal damage. Iba1, OX18 and OX42, which are constitutively expressed, were good markers both for activation and proliferation. ED1 was early and persistently up regulated. Preliminary data indicate that MHC-II was upregulated at an early stage but disappeared at later time points. Furthermore, the data revealed marked differences in MHC-II expression between the optic nerve and the retina, which might be explained by the immune-privilege of the eye. Early and sustained upregulation of nestin and the small heat-shock proteins alphaB-crystallin and heat-shock protein 27 was observed in astrocytes. Interestingly, increased expression was also observed in the contralateral optic nerve. This might be explained by the syncytial structure of these cells.
Increasing evidence exists that the influence of glial cells might be pivotal in determining neuronal survival or demise. Further studies are needed to elucidate the role of these cell populations in neurodegenerative retinal and optic pathway diseases.
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