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Updated: Aug 26, 2025
A Magnetic Microbead Occlusion Model to Induce Ocular Hypertension-Dependent Glaucoma in Mice
Published on: March 23, 2016
Microglia depletion exacerbates retinal ganglion cell loss in a mouse model of glaucoma
Zizhu Tan1, Yinjie Guo2, Maleeka Shrestha3
1The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China; Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard University School of Medicine, 20 Staniford Street, Boston, MA, 02114, USA.
Abstract:
To test whether depletion of microglia in the optic nerve head has a beneficial effect on retinal ganglion cell numbers and function, we depleted microglia by oral administration of the CSF1R antagonist PLX5622. Then, ocular hypertension was induced by unilateral injection of magnetic microbeads into the anterior chamber. Visual function was assessed with pattern electroretinography and measurement of the optomotor reflex. Retinal ganglion cell bodies and axons were counted and gene expression patterns in optic nerve head astrocytes were tested on freshly dissociated astrocytes. PLX5622 efficiently depleted microglia in the retina and the optic nerve head, but about 20% of microglia persisted in the myelinated optic nerve proper even after prolonged exposure to the drug. PLX5622 did not affect ganglion cell function by itself. Elevation of the IOP for four weeks led to the expected decrease in visual acuity and pattern ERG amplitude. Microglia ablation did not affect these parameters. Ganglion cell and axon numbers were counted histologically post mortem. Mice in the microglia depletion group showed a moderate but significantly greater loss of ganglion cells than the control group. At four weeks post microbead injection, gene expression patterns in optic nerve head astrocytes are consistent with an A2 (or neuroprotective) pattern. Microglia depletion blunted the up-regulation of A2 genes in astrocytes. In conclusion, microglia depletion is unlikely to protect retinal ganglion cells in early glaucoma.
Insights
Depleting microglia in the optic nerve head did not protect retinal ganglion cells from glaucoma-induced damage. In fact, microglia depletion worsened ganglion cell loss and blunted neuroprotective gene expression in astrocytes.
Area of Science:
- Neuroscience
- Ophthalmology
- Immunology
Background:
- Microglia play complex roles in central nervous system inflammation and injury.
- Their role in protecting retinal ganglion cells (RGCs) in glaucoma is not fully understood.
Purpose of the Study:
- To investigate the therapeutic potential of microglia depletion in a mouse model of ocular hypertension and glaucoma.
- To assess the impact of microglia ablation on RGC survival, function, and optic nerve head astrocyte gene expression.
Main Methods:
- Microglia were depleted orally using the CSF1R antagonist PLX5622.
- Ocular hypertension was induced via microbead injection into the anterior chamber.
- Visual function, RGC numbers, and astrocyte gene expression were analyzed.
Main Results:
- PLX5622 effectively depleted microglia in the retina and optic nerve head, with some persistence in the optic nerve proper.
- Microglia depletion did not prevent vision loss or RGC dysfunction induced by ocular hypertension.
- Mice with depleted microglia exhibited a greater loss of RGCs and blunted upregulation of neuroprotective astrocyte genes.
Conclusions:
- Microglia depletion is unlikely to be a protective strategy for RGCs in early glaucoma.
- The findings suggest that microglia may have a neuroprotective role in this glaucoma model.
