Early reduction of microglia activation by irradiation in a model of chronic glaucoma.

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...

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Main Authors: Alejandra Bosco, Samuel D Crish, Michael R Steele, Cesar O Romero, Denise M Inman, Philip J Horner, David J Calkins, Monica L Vetter
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3431380?pdf=render
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author Alejandra Bosco
Samuel D Crish
Michael R Steele
Cesar O Romero
Denise M Inman
Philip J Horner
David J Calkins
Monica L Vetter
author_facet Alejandra Bosco
Samuel D Crish
Michael R Steele
Cesar O Romero
Denise M Inman
Philip J Horner
David J Calkins
Monica L Vetter
author_sort Alejandra Bosco
collection DOAJ
description 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.
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spelling doaj.art-3a10033f1acd459c89a9afb505aa51fa2022-12-22T00:48:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4360210.1371/journal.pone.0043602Early reduction of microglia activation by irradiation in a model of chronic glaucoma.Alejandra BoscoSamuel D CrishMichael R SteeleCesar O RomeroDenise M InmanPhilip J HornerDavid J CalkinsMonica L VetterGlaucoma 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.http://europepmc.org/articles/PMC3431380?pdf=render
spellingShingle Alejandra Bosco
Samuel D Crish
Michael R Steele
Cesar O Romero
Denise M Inman
Philip J Horner
David J Calkins
Monica L Vetter
Early reduction of microglia activation by irradiation in a model of chronic glaucoma.
PLoS ONE
title Early reduction of microglia activation by irradiation in a model of chronic glaucoma.
title_full Early reduction of microglia activation by irradiation in a model of chronic glaucoma.
title_fullStr Early reduction of microglia activation by irradiation in a model of chronic glaucoma.
title_full_unstemmed Early reduction of microglia activation by irradiation in a model of chronic glaucoma.
title_short Early reduction of microglia activation by irradiation in a model of chronic glaucoma.
title_sort early reduction of microglia activation by irradiation in a model of chronic glaucoma
url http://europepmc.org/articles/PMC3431380?pdf=render
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