Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy

Background: To analyze the course of microglial and macroglial activation in injured and contralateral retinas after unilateral optic nerve crush (ONC). Methods: The left optic nerve of adult pigmented C57Bl/6 female mice was intraorbitally crushed and injured, and contralateral retinas were analyze...

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Main Authors: María José González-Riquelme, Caridad Galindo-Romero, Fernando Lucas-Ruiz, Marina Martínez-Carmona, Kristy T. Rodríguez-Ramírez, José María Cabrera-Maqueda, María Norte-Muñoz, Manuel Vidal-Sanz, Marta Agudo-Barriuso
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/16/8517
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author María José González-Riquelme
Caridad Galindo-Romero
Fernando Lucas-Ruiz
Marina Martínez-Carmona
Kristy T. Rodríguez-Ramírez
José María Cabrera-Maqueda
María Norte-Muñoz
Manuel Vidal-Sanz
Marta Agudo-Barriuso
author_facet María José González-Riquelme
Caridad Galindo-Romero
Fernando Lucas-Ruiz
Marina Martínez-Carmona
Kristy T. Rodríguez-Ramírez
José María Cabrera-Maqueda
María Norte-Muñoz
Manuel Vidal-Sanz
Marta Agudo-Barriuso
author_sort María José González-Riquelme
collection DOAJ
description Background: To analyze the course of microglial and macroglial activation in injured and contralateral retinas after unilateral optic nerve crush (ONC). Methods: The left optic nerve of adult pigmented C57Bl/6 female mice was intraorbitally crushed and injured, and contralateral retinas were analyzed from 1 to 45 days post-lesion (dpl) in cross-sections and flat mounts. As controls, intact retinas were studied. Iba1<sup>+</sup> microglial cells (MCs), activated phagocytic CD68<sup>+</sup>MCs and M2 CD206<sup>+</sup>MCs were quantified. Macroglial cell changes were analyzed by GFAP and vimentin signal intensity. Results: After ONC, MC density increased significantly from 5 to 21 dpl in the inner layers of injured retinas, remaining within intact values in the contralateral ones. However, in both retinas there was a significant and long-lasting increase of CD68<sup>+</sup>MCs. Constitutive CD206<sup>+</sup>MCs were rare and mostly found in the ciliary body and around the optic-nerve head. While in the injured retinas their number increased in the retina and ciliary body, in the contralateral retinas decreased. Astrocytes and Müller cells transiently hypertrophied in the injured retinas and to a lesser extent in the contralateral ones. Conclusions: Unilateral ONC triggers a bilateral and persistent activation of MCs and an opposed response of M2 MCs between both retinas. Macroglial hypertrophy is transient.
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spelling doaj.art-f56b788ec50c49d69bdba79f21d6926d2023-11-22T07:56:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216851710.3390/ijms22168517Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral AxotomyMaría José González-Riquelme0Caridad Galindo-Romero1Fernando Lucas-Ruiz2Marina Martínez-Carmona3Kristy T. Rodríguez-Ramírez4José María Cabrera-Maqueda5María Norte-Muñoz6Manuel Vidal-Sanz7Marta Agudo-Barriuso8Grupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainGrupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30120 Murcia, SpainBackground: To analyze the course of microglial and macroglial activation in injured and contralateral retinas after unilateral optic nerve crush (ONC). Methods: The left optic nerve of adult pigmented C57Bl/6 female mice was intraorbitally crushed and injured, and contralateral retinas were analyzed from 1 to 45 days post-lesion (dpl) in cross-sections and flat mounts. As controls, intact retinas were studied. Iba1<sup>+</sup> microglial cells (MCs), activated phagocytic CD68<sup>+</sup>MCs and M2 CD206<sup>+</sup>MCs were quantified. Macroglial cell changes were analyzed by GFAP and vimentin signal intensity. Results: After ONC, MC density increased significantly from 5 to 21 dpl in the inner layers of injured retinas, remaining within intact values in the contralateral ones. However, in both retinas there was a significant and long-lasting increase of CD68<sup>+</sup>MCs. Constitutive CD206<sup>+</sup>MCs were rare and mostly found in the ciliary body and around the optic-nerve head. While in the injured retinas their number increased in the retina and ciliary body, in the contralateral retinas decreased. Astrocytes and Müller cells transiently hypertrophied in the injured retinas and to a lesser extent in the contralateral ones. Conclusions: Unilateral ONC triggers a bilateral and persistent activation of MCs and an opposed response of M2 MCs between both retinas. Macroglial hypertrophy is transient.https://www.mdpi.com/1422-0067/22/16/8517M1M2microglial cellsoptic nerve crushretinainflammation
spellingShingle María José González-Riquelme
Caridad Galindo-Romero
Fernando Lucas-Ruiz
Marina Martínez-Carmona
Kristy T. Rodríguez-Ramírez
José María Cabrera-Maqueda
María Norte-Muñoz
Manuel Vidal-Sanz
Marta Agudo-Barriuso
Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy
International Journal of Molecular Sciences
M1
M2
microglial cells
optic nerve crush
retina
inflammation
title Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy
title_full Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy
title_fullStr Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy
title_full_unstemmed Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy
title_short Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy
title_sort axonal injuries cast long shadows long term glial activation in injured and contralateral retinas after unilateral axotomy
topic M1
M2
microglial cells
optic nerve crush
retina
inflammation
url https://www.mdpi.com/1422-0067/22/16/8517
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