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Updated: Oct 23, 2025
An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival
Published on: April 25, 2011
Sigma-1R Protects Retinal Ganglion Cells in Optic Nerve Crush Model for Glaucoma
Linya Li1, Shaoqing He2, Yang Liu1,2
1Department of Pharmacology and Neuroscience University of North Texas Health Science Center, Fort Worth, Texas, United States.
Purpose:
The purpose of this study was to determine the effects of the Sigma-1R (σ-1r) on retinal ganglion cell (RGC) survival following optic nerve crush (ONC) and the signaling mechanism involved in the σ-1r protection.
Methods:
The overall strategy was to induce injury by ONC and mitigate RGC death by increasing σ-1r expression and/or activate σ-1r activity in σ-1r K/O mice and wild type (WT) mice. AAV2-σ-1r vector was used to increase σ-1r expression and σ-1r agonist used to activate the σ-1r and RGCs were counted. Immunohistochemical and Western blot analysis determined phosphorylated (p)-c-Jun, c-Jun, and Caspase-3. Pattern electroretinography (PERG) determined RGC activity.
Results:
RGC counts and function were similar in pentazocine-treated WT mice when compared to untreated mice and in WT mice when compared with σ-1r K/O mice. Pentazocine-induced effects and the effects of σ-1r K/O were only observable after ONC. ONC resulted in decreased RGC counts and activity in both WT and σ-1r K/O mice, with σ-1r K/O mice experiencing significant decreases compared with WT mice. The σ-1r transgenic expression resulted in increased RGC counts and activity following ONC. In WT mice, treatment with σ-1r agonist pentazocine resulted in increased RGC counts and increased activity when compared with untreated WT mice. There were time-dependent increases in c-jun, p-c-jun, and caspase-3 expression in ONC mice that were mitigated with pentazocine-treatment.
Conclusions:
These findings suggest that the apoptotic pathway is involved in RGC losses seen in an ONC model. The σ-1r offers neuroprotection, as activation and/or transgenic expression of σ-1r attenuated the apoptotic pathway and restored RGCs number and function following ONC.
Insights
The Sigma-1R (σ-1r) receptor protects retinal ganglion cells (RGCs) after optic nerve crush (ONC). Activating or increasing σ-1r expression preserves RGCs by reducing apoptosis.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Retinal ganglion cells (RGCs) are crucial for vision.
- Optic nerve crush (ONC) is a common model for studying optic nerve injury and RGC degeneration.
- The Sigma-1R (σ-1r) is a unique intracellular chaperone protein implicated in various cellular functions, including neuroprotection.
Purpose of the Study:
- To investigate the neuroprotective effects of the Sigma-1R (σ-1r) on retinal ganglion cell (RGC) survival after optic nerve crush (ONC).
- To elucidate the signaling mechanisms underlying σ-1r-mediated protection in the context of ONC.
Main Methods:
- Optic nerve crush (ONC) was induced in wild-type (WT) and σ-1r knockout (K/O) mice.
- σ-1r expression was increased using AAV2-σ-1r vectors, and σ-1r activity was modulated using the agonist pentazocine.
- RGC survival and function were assessed via cell counting and pattern electroretinography (PERG).
- Apoptotic markers (p-c-Jun, c-Jun, Caspase-3) were analyzed using immunohistochemistry and Western blotting.
Main Results:
- ONC led to significant RGC loss and functional decline in both WT and σ-1r K/O mice, with greater severity in σ-1r K/O mice.
- Transgenic overexpression or agonist-induced activation of σ-1r significantly increased RGC counts and improved function post-ONC.
- Pentazocine treatment mitigated the time-dependent increases in apoptotic markers (c-Jun, p-c-Jun, Caspase-3) following ONC.
Conclusions:
- The apoptotic pathway plays a critical role in RGC loss following ONC.
- Sigma-1R (σ-1r) activation or increased expression confers significant neuroprotection to RGCs after optic nerve injury.
- Targeting σ-1r represents a promising therapeutic strategy for preserving vision in conditions involving optic nerve damage.
