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Updated: Dec 21, 2025
An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival
Published on: April 25, 2011
Longitudinal Morphological and Functional Assessment of RGC Neurodegeneration After Optic Nerve Crush in Mouse
Liang Li1, Haoliang Huang1, Fang Fang1,2
1Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, United States.
Abstract:
The mouse optic nerve crush (ONC) model has been widely used to study optic neuropathies and central nervous system (CNS) axon injury and repair. Previous histological studies of retinal ganglion cell (RGC) somata in retina and axons in ON demonstrate significant neurodegeneration after ONC, but longitudinal morphological and functional assessment of RGCs in living animals is lacking. It is essential to establish these assays to provide more clinically relevant information for early detection and monitoring the progression of CNS neurodegeneration. Here, we present in vivo data gathered by scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and pattern electroretinogram (PERG) at different time points after ONC in mouse eyes and corresponding histological quantification of the RGC somata and axons. Not surprisingly, direct visualization of RGCs by SLO fundus imaging correlated best with histological quantification of RGC somata and axons. Unexpectedly, OCT did not detect obvious retinal thinning until late time points (14 and 28-days post ONC) and instead detected significant retinal swelling at early time points (1-5 days post-ONC), indicating a characteristic initial retinal response to ON injury. PERG also demonstrated an early RGC functional deficit in response to ONC, before significant RGC death, suggesting that it is highly sensitive to ONC. However, the limited progression of PERG deficits diminished its usefulness as a reliable indicator of RGC degeneration.
Insights
This study evaluated in vivo imaging and electrophysiology to assess optic nerve crush injury in mice. While scanning laser ophthalmoscopy best correlated with RGC loss, optical coherence tomography revealed early swelling, and pattern electroretinograms showed initial functional deficits.
Area of Science:
- Neuroscience
- Ophthalmology
- Regenerative Medicine
Background:
- The mouse optic nerve crush (ONC) model is crucial for studying central nervous system (CNS) axon injury and optic neuropathies.
- Longitudinal assessment of retinal ganglion cells (RGCs) in living animals after ONC is lacking, hindering clinical relevance for early detection and monitoring.
Purpose of the Study:
- To establish and validate in vivo assays for longitudinal assessment of RGCs following ONC in mice.
- To compare the efficacy of scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and pattern electroretinogram (PERG) in monitoring RGC degeneration and function post-ONC.
Main Methods:
- Utilized SLO, OCT, and PERG to longitudinally assess RGCs in mouse eyes after ONC.
- Correlated in vivo findings with ex vivo histological quantification of RGC somata and axons.
Main Results:
- SLO fundus imaging showed strong correlation with histological RGC counts.
- OCT revealed early retinal swelling (1-5 days post-ONC) rather than thinning, which appeared late (14-28 days).
- PERG detected early RGC functional deficits preceding significant cell death, but progression was limited, reducing its reliability for monitoring degeneration.
Conclusions:
- SLO is a reliable in vivo method for assessing RGC survival post-ONC.
- OCT provides insights into early retinal responses, specifically swelling, after optic nerve injury.
- PERG is sensitive to early functional changes but less effective for long-term monitoring of RGC degeneration in this model.
