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Updated: Feb 15, 2026

An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival
Published on: April 25, 2011
Early Gene Expression Profile in Retinal Ganglion Cell Layer After Optic Nerve Crush in Mice
Satoru Ueno1, Azusa Yoneshige2, Yoshiki Koriyama3
1Department of Ophthalmology, Faculty of Medicine, Kindai University, Osaka, Japan.
Purpose:
Optic nerve crush (ONC) induces retinal ganglion cell (RGC) death, which causes vision loss in glaucoma. To investigate early events leading to apoptosis of RGCs, we performed gene expression analysis of injured retinas in the period before RGC loss.
Methods:
The temporal changes of gene profiles at 0, 1, and 4 days after ONC were determined by DNA microarray. To verify the gene expression changes in RGCs, we enriched RGCs by laser-captured microdissection and performed real-time RT-PCR of 14 selected genes. In situ localization study was performed by immunohistochemistry.
Results:
At 1 day and 4 days after ONC, 1423 and 2010 retinal genes were changed compared with 0 day, respectively; these genes were mainly related to apoptotic process, immune process, regulation of cell cycle, and ion transport. RT-PCR analysis revealed that expression levels of Activating transcription factor 3 (Atf3), Lipocalin 2 (Lcn2), and tumor necrosis factor receptor superfamily member 12a (Tnfrsf12a) were remarkably changed in RGC-enriched fraction within 4 days postcrush. Immunohistochemical analysis confirmed that all of these genes expressed highly in the ganglion cell layer of crushed retinas.
Conclusions:
In response to ONC, the expression of apoptotic genes was stimulated soon after crush. Atf3, Lcn2, and Tnfrsf12a might be key molecules responsible for RGC loss in glaucoma.
Insights
Optic nerve crush (ONC) triggers early apoptotic gene expression in retinal ganglion cells (RGCs). Key genes like Atf3, Lcn2, and Tnfrsf12a may drive RGC loss in glaucoma.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Glaucoma is characterized by retinal ganglion cell (RGC) death, leading to vision loss.
- Optic nerve crush (ONC) is a model used to study RGC apoptosis and its underlying mechanisms.
Purpose of the Study:
- To investigate the early molecular events and gene expression changes preceding RGC loss after ONC.
- To identify key genes involved in the apoptotic pathway of RGCs following injury.
Main Methods:
- Gene expression profiling using DNA microarray at 0, 1, and 4 days post-ONC.
- RGC enrichment via laser-captured microdissection followed by real-time RT-PCR for selected genes.
- In situ gene expression localization using immunohistochemistry.
Main Results:
- Significant changes in 1423 and 2010 retinal genes were observed at 1 and 4 days post-ONC, respectively.
- Genes related to apoptosis, immune response, cell cycle regulation, and ion transport were predominantly affected.
- Expression of Activating transcription factor 3 (Atf3), Lipocalin 2 (Lcn2), and tumor necrosis factor receptor superfamily member 12a (Tnfrsf12a) were significantly upregulated in RGCs within 4 days.
Conclusions:
- Apoptotic gene expression is rapidly induced following ONC.
- Atf3, Lcn2, and Tnfrsf12a are identified as potential key mediators of RGC death in glaucoma.
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