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Microglial dynamics after axotomy-induced retinal ganglion cell death

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dc.contributor.authorNadal-Nicolás, Francisco Manuel
dc.contributor.authorJiménez-López, Manuel
dc.contributor.authorSalinas Navarro, Manuel Ángel
dc.contributor.authorSobrado Calvo, Paloma
dc.contributor.authorVidal Sanz, Manuel
dc.contributor.authorAgudo Barriuso, Marta
dc.contributor.departmentOftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
dc.contributor.otherFacultad de Medicina
dc.date.accessioned2026-01-27T20:16:17Z
dc.date.available2026-01-27T20:16:17Z
dc.date.copyright© 2017 The Author(s)
dc.date.issued2017-11-09
dc.description.abstractBackground: Microglial cells (MCs) are the sentries of the central nervous system. In health, they are known as surveying MCs because they examine the tissue to maintain the homeostasis. In disease, they activate and, among other functions, become phagocytic to clean the cellular debris. In this work, we have studied the behavior of rat retinal MCs in two models of unilateral complete intraorbital optic nerve axotomy which elicit a different time course of retinal ganglion cell (RGC) loss. Methods: Albino Sprague-Dawley rats were divided into these groups: (a) intact (no surgery), (b) fluorogold (FG) tracing from the superior colliculi, and (c) FG tracing + crush or transection of the left optic nerve. The retinas were dissected from 2 days to 2 months after the lesions (n = 4-12 group/lesion and time point) and then were subjected to Brn3a and Iba1 double immunodetection. In each intact retina, the total number of Brn3a+RGCs and Iba+MCs was quantified. In each traced retina (b and c groups), FG-traced RGCs and phagocytic microglial cells (PMCs, FG+Iba+) were also quantified. Topographical distribution was assessed by neighbor maps. Results: In intact retinas, surveying MCs are homogenously distributed in the ganglion cell layer and the inner plexiform layer. Independently of the axotomy model, RGC death occurs in two phases, one quick and one protracted, and there is a lineal and topographical correlation between the appearance of PMCs and the loss of traced RGCs. Furthermore, the clearance of FG+RGCs by PMCs occurs 3 days after the actual loss of Brn3a expression that marks RGC death. In addition, almost 50% of MCs from the inner plexiform layer migrate to the ganglion cell layer during the quick phase of RGC loss, returning to the inner plexiform layer during the slow degeneration phase. Finally, in contrast to what happens in mice, in rats, there is no microglial phagocytosis in the contralateral uninjured retina. Conclusions: Axotomy-induced RGC death occurs earlier than RGC clearance and there is an inverse correlation between RGC loss and PMC appearance, both numerically and topographically, suggesting that phagocytosis occurs as a direct response to RGC death rather than to axonal damage.
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dc.format.extent15
dc.identifier.citationJ Neuroinflammation. 2017 Nov 9;14(1):218
dc.identifier.doihttps://doi.org/10.1186/s12974-017-0982-7
dc.identifier.eissn1742-2094
dc.identifier.urihttp://hdl.handle.net/10201/195569
dc.languageeng
dc.publisherBioMed Central
dc.relationThis study was funded by Fundación Séneca, Agencia de Ciencia y Tecnología Región de Murcia (19881/GERM/15), and the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional “Una Manera de Hacer Europa” (SAF2015-67643-P, PI16/00031).
dc.relation.publisherversionhttps://link.springer.com/article/10.1186/s12974-017-0982-7
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectFluorogold
dc.subjectTranscellular labeling
dc.subjectIba1
dc.subjectMigration
dc.subjectPhagocyte
dc.subjectBrn3a
dc.subject.odsObjetivo 3: Salud
dc.titleMicroglial dynamics after axotomy-induced retinal ganglion cell death
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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