Early Reduction of Microglia Activation by Irradiation in a Model of Chronic Glaucoma
Open Access
- 30 August 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (8), e43602
- https://doi.org/10.1371/journal.pone.0043602
Abstract
Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, the mechanisms leading to onset and progression of the disease remain unknown. Molecular analysis in various glaucoma models has revealed involvement of non-neuronal cell populations, including astrocytes, Mueller glia and microglia, at early stages of glaucoma. High-dose irradiation was reported to have a significant long-term protective effect in the DBA/2J (D2) mouse model of glaucoma, although the cellular and molecular basis for this effect remains unclear. In particular, the acute effects of irradiation on specific cell populations, including non-neuronal cells, in the D2 retina and nerve have not been assessed. Here we report that irradiation induces transient reduction in proliferating microglia within the optic nerve head and glial lamina within the first week post-irradiation. This was accompanied by reduced microglial activation, with no effect on astrocyte gliosis in those regions. At later stages we confirm that early high-dose irradiation of the mouse head results in improvement of axonal structural integrity and anterograde transport function, without reduction of intraocular pressure. Thus reduced microglial activation induced by irradiation at early stages is associated with reduced optic nerve and retinal neurodegeneration in the D2 mouse model of glaucoma.Keywords
This publication has 57 references indexed in Scilit:
- Physiopathology of radiation-induced neurotoxicityRevue Neurologique, 2011
- Early microglia activation in a mouse model of chronic glaucomaJournal of Comparative Neurology, 2010
- Distal axonopathy with structural persistence in glaucomatous neurodegenerationProceedings of the National Academy of Sciences of the United States of America, 2010
- Loss of Neuronal Protein Expression in Mouse Hippocampus After IrradiationJournal of Neuropathology and Experimental Neurology, 2010
- The Microbead Occlusion Model: A Paradigm for Induced Ocular Hypertension in Rats and MiceInvestigative Ophthalmology & Visual Science, 2010
- Characteristics of Bone Marrow–Derived Microglia in the Normal and Injured RetinaInvestigative Ophthalmology & Visual Science, 2008
- Local self-renewal can sustain CNS microglia maintenance and function throughout adult lifeNature Neuroscience, 2007
- The number of people with glaucoma worldwide in 2010 and 2020British Journal of Ophthalmology, 2006
- Quantitative Correlation of Optic Nerve Pathology with Ocular Pressure and Corneal Thickness in the DBA/2 Mouse Model of GlaucomaInvestigative Ophthalmology & Visual Science, 2006
- Microglia in the optic nerve head and the region of parapapillary chorioretinal atrophy in glaucoma.American Journal of Ophthalmology, 1999