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

轴突损伤投射出长长的阴影:单侧轴突切断术后损伤视网膜和对侧视网膜中的长期胶质细胞激活

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作者: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

Background

To analyze the course of microglial and macroglial activation in injured and contralateral retinas after unilateral optic nerve crush (ONC).

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.

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+ microglial cells (MCs), activated phagocytic CD68+MCs and M2 CD206+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+MCs. Constitutive CD206+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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