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A Magnetic Microbead Occlusion Model to Induce Ocular Hypertension-Dependent Glaucoma in Mice
Published on: March 23, 2016
Microglia depletion leads to increased susceptibility to ocular hypertension-dependent glaucoma
Cory A Diemler1,2, Michael MacLean1, Sarah E Heuer1,3
1The Jackson Laboratory, Bar Harbor, ME, United States.
Abstract:
In recent years, microglia have been highlighted for playing integral roles in neurodegenerative diseases, like glaucoma. To better understand the role of microglia during chronic ocular hypertension, we depleted microglia from aged (9-12 months old) DBA/2 J (D2) mice, which exhibit age-related increases in intraocular pressure, using a dietary CSF1R antagonist, PLX5622. Retinal ganglion cell (RGC) somas were counted, and optic nerve cross-sections stained and assessed for glaucomatous damage. Sustained administration of dietary PLX5622 significantly reduced the numbers of retinal microglia. Dietary PLX5622 did not lead to changes in intraocular pressure in D2 or normotensive DBA/2 J-Gpnmb (D2-Gpnmb ) control mice. While PLX5622-treated D2-Gpnmb did not develop optic nerve damage, PLX5622-treated D2 mice showed a significant increase in moderate-to-severe optic nerve damage compared to D2 mice fed a control diet. In conclusion, global reduction of microglia exacerbated glaucomatous neurodegeneration in D2 mice suggesting microglia play an overall beneficial role in protecting from ocular hypertension associated RGC loss.
Insights
Reducing microglia, the immune cells of the eye, worsened glaucoma-related nerve damage in mice. This suggests microglia play a protective role against ocular hypertension and retinal ganglion cell loss.
Area of Science:
- Neuroscience
- Ophthalmology
- Immunology
Background:
- Microglia are key players in neurodegenerative diseases, including glaucoma.
- Glaucoma involves chronic ocular hypertension and retinal ganglion cell (RGC) loss.
- The specific role of microglia in glaucoma pathogenesis remains under investigation.
Purpose of the Study:
- To investigate the role of microglia in glaucomatous neurodegeneration.
- To determine if microglia depletion exacerbates optic nerve damage in a mouse model of ocular hypertension.
Main Methods:
- Aged DBA/2J mice, prone to ocular hypertension, were treated with a CSF1R antagonist (PLX5622) to deplete microglia.
- Intraocular pressure (IOP), RGC somas, and optic nerve damage were assessed.
- Control groups included normotensive DBA/2J-Gpnmb mice.
Main Results:
- Dietary PLX5622 effectively reduced retinal microglia numbers without altering IOP.
- Microglia depletion did not cause damage in normotensive controls.
- PLX5622-treated DBA/2J mice exhibited significantly increased optic nerve damage compared to controls.
Conclusions:
- Global reduction of microglia exacerbated glaucomatous neurodegeneration.
- These findings suggest microglia play a neuroprotective role in ocular hypertension.
- Targeting microglia may have complex implications for glaucoma treatment.
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