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Updated: May 20, 2026
In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma
Published on: May 11, 2015
The Bcl-2 family member BIM has multiple glaucoma-relevant functions in DBA/2J mice
Jeffrey M Harder1, Kimberly A Fernandes, Richard T Libby
1Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
Abstract:
Axonal insult induces retinal ganglion cell (RGC) death through a BAX-dependent process. The pro-apoptotic Bcl-2 family member BIM is known to induce BAX activation. BIM expression increased in RGCs after axonal injury and its induction was dependent on JUN. Partial and complete Bim deficiency delayed RGC death after mechanical optic nerve injury. However, in a mouse model of glaucoma, DBA/2J mice, Bim deficiency did not prevent RGC death in eyes with severe optic nerve degeneration. In a subset of DBA/2J mice, Bim deficiency altered disease progression resulting in less severe nerve damage. Bim deficient mice exhibited altered optic nerve head morphology and significantly lessened intraocular pressure elevation. Thus, a decrease in axonal degeneration in Bim deficient DBA/2J mice may not be caused by a direct role of Bim in RGCs. These data suggest that BIM has multiple roles in glaucoma pathophysiology, potentially affecting susceptibility to glaucoma through several mechanisms.
Insights
BIM deficiency delayed retinal ganglion cell death after optic nerve injury but did not prevent it in glaucoma models. In DBA/2J mice, Bim deficiency altered glaucoma progression, suggesting multiple roles for BIM in eye disease.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Axonal injury triggers retinal ganglion cell (RGC) death via BAX activation.
- The pro-apoptotic protein BIM promotes BAX activation and is upregulated after axonal injury, dependent on JUN.
- Previous studies showed Bim deficiency delays RGC death after mechanical optic nerve injury.
Purpose of the Study:
- To investigate the role of BIM in RGC death and glaucoma pathophysiology.
- To determine if BIM deficiency impacts disease progression in a genetic glaucoma mouse model (DBA/2J).
Main Methods:
- Utilized mechanical optic nerve injury models to assess RGC survival in Bim-deficient mice.
- Examined DBA/2J mice with genetic glaucoma, comparing Bim-deficient and wild-type littermates.
- Assessed RGC survival, optic nerve damage, optic nerve head morphology, and intraocular pressure.
Main Results:
- Bim deficiency delayed RGC death following mechanical optic nerve injury.
- In DBA/2J mice, Bim deficiency did not prevent RGC death in advanced glaucoma but altered disease progression in a subset of mice.
- Bim deficiency in DBA/2J mice led to less severe optic nerve damage, altered optic nerve head morphology, and reduced intraocular pressure elevation.
Conclusions:
- BIM has a direct role in RGC death following mechanical injury.
- In the context of glaucoma, BIM's role is complex, potentially influencing susceptibility through mechanisms beyond direct RGC apoptosis, such as affecting intraocular pressure and optic nerve head pathology.
- These findings suggest BIM is a potential therapeutic target for glaucoma, with multifaceted roles in disease pathogenesis.
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