Microglial dynamics after axotomy-induced retinal ganglion cell death
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Updated: Feb 19, 2026
Optic Nerve Transection: A Model of Adult Neuron Apoptosis in the Central Nervous System
Published on: May 12, 2011
Francisco M Nadal-Nicolás1,2,3, Manuel Jiménez-López4,5, Manuel Salinas-Navarro4,5
1Grupo de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca, Edificio LAIB Planta 5ª, Carretera Buenavista s/n, 30120, El Palmar, Murcia, Spain. fm.nadalnicolas@um.es.
Background:
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.
Insights
Microglial cells (MCs) clear dead retinal ganglion cells (RGCs) after optic nerve injury. Phagocytosis by MCs directly responds to RGC death, not axonal damage, with clearance occurring after RGC loss.
Area of Science:
- Neuroscience
- Ophthalmology
- Immunology
Background:
- Microglial cells (MCs) are the primary immune cells of the central nervous system.
- In the retina, MCs survey tissue and become phagocytic to clear cellular debris during injury.
- Optic nerve axotomy in rats causes retinal ganglion cell (RGC) loss, prompting investigation into MC behavior.
Purpose of the Study:
- To investigate the behavior and phagocytic activity of rat retinal microglial cells following optic nerve axotomy.
- To determine the temporal relationship between retinal ganglion cell death and microglial phagocytosis.
- To analyze the topographical distribution of phagocytic microglial cells in response to RGC loss.
Main Methods:
- Two models of unilateral optic nerve axotomy (crush or transection) were used in Sprague-Dawley rats.
- Retinas were analyzed 2 days to 2 months post-lesion using Brn3a and Iba1 double immunodetection.
- Fluorogold (FG) tracing identified RGCs, and phagocytic microglial cells (PMCs) were quantified as FG+Iba1+ cells.
Main Results:
- RGC death occurred in two phases: a rapid and a protracted phase.
- Phagocytic microglial cell (PMC) appearance correlated linearly and topographically with RGC loss.
- PMC-mediated clearance of RGCs occurred approximately 3 days after RGC death, indicating a delayed response.
Conclusions:
- Optic nerve axotomy triggers RGC death preceding microglial clearance.
- An inverse numerical and topographical correlation exists between RGC loss and PMC appearance.
- Microglial phagocytosis is a direct response to RGC death, not axonal damage itself.
