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Updated: Aug 2, 2025
An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival
Published on: April 25, 2011
Rapamycin suppresses neuroinflammation and protects retinal ganglion cell loss after optic nerve crush
Feifei Wang1, Yuning Song1, Peiyu Liu1
1Affiliated Eye Hospital of Nanchang University, Nanchang University School of Ophthalmology & Optometry, Jiangxi Provincial Key Laboratory for Ophthalmology, Jiangxi Research Institute of Ophthalmology & Visual Science, Nanchang 330006, PR China.
Abstract:
Pyroptosis, an inflammasome-mediated mode of death, plays an important role in glaucoma. It has been shown that regulating the mTOR pathway can inhibit pyroptosis. Unfortunately, whether rapamycin (RAPA), a specific inhibitor of the mTOR pathway, can inhibit optic nerve crush (ONC)-induced pyroptosis to protect retinal ganglion cells (RGCs) has not been investigated. Our research aimed to confirm the effect of intravitreal injection of RAPA on RGCs. Furthermore, we used the ONC model to explore the underlying mechanisms. First, we observed that intravitreal injection of RAPA alleviated RGC damage induced by various types of injury. We then used the ONC model to further explore the potential mechanism of RAPA. Mechanistically, RAPA not only reduced the activation of glial cells in the retina but also inhibited retinal pyroptosis-induced expression of inflammatory factors such as nucleotide-binding oligomeric domain-like receptor 3 (NLRP3), apoptosis-associated speckle-like protein containing a CARD (ASC), N-terminal of gasdermin-D (GSDMD-N), IL-18 and IL-1β. Moreover, RAPA exerted protective effects on RGC axons, possibly by inhibiting glial activation and regulating the mTOR/ROCK pathway. Therefore, this study demonstrates a novel mechanism by which RAPA protects against glaucoma and provides further evidence for its application in preclinical studies.
Insights
Rapamycin (RAPA) injection protects retinal ganglion cells (RGCs) in glaucoma models by inhibiting pyroptosis, a key cell death pathway. This study reveals RAPA
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Pyroptosis, an inflammasome-mediated cell death, is implicated in glaucoma pathogenesis.
- The mechanistic target of rapamycin (mTOR) pathway is known to regulate pyroptosis.
- The neuroprotective potential of rapamycin (RAPA) against optic nerve crush (ONC)-induced pyroptosis in glaucoma remains unexplored.
Purpose of the Study:
- To investigate the effect of intravitreal rapamycin (RAPA) on retinal ganglion cells (RGCs) in glaucoma.
- To elucidate the underlying mechanisms by which RAPA protects RGCs in an optic nerve crush (ONC) model.
- To explore RAPA's potential in mitigating glaucoma-associated RGC damage.
Main Methods:
- Intravitreal injection of RAPA in an optic nerve crush (ONC) glaucoma model.
- Assessment of RGC survival and axonal protection.
- Analysis of glial cell activation and pyroptosis-related inflammatory markers (NLRP3, ASC, GSDMD-N, IL-18, IL-1β).
- Investigation of the mTOR/ROCK pathway.
Main Results:
- Intravitreal RAPA alleviated RGC damage across various injury types.
- RAPA significantly reduced glial cell activation in the retina.
- RAPA inhibited the expression of key pyroptosis markers (NLRP3, ASC, GSDMD-N) and inflammatory cytokines (IL-18, IL-1β).
- RAPA demonstrated protective effects on RGC axons.
Conclusions:
- Rapamycin (RAPA) exerts neuroprotective effects in glaucoma by inhibiting pyroptosis and inflammation.
- RAPA mitigates RGC damage and axonal loss, potentially via mTOR/ROCK pathway regulation and glial activation inhibition.
- This study supports RAPA's potential as a therapeutic agent for glaucoma in preclinical settings.
