Related Experiment Video
Updated: Aug 24, 2026
A Surgical Approach for Optic Nerve Crush in a Rabbit Model
Published on: July 8, 2025
Reduction of Lipid Droplets Modulates the Injury Response and Enhances CNTF-Induced Axon Regeneration Following Optic
Xiaowei Fan1, Ruyue Li2, Shen Wu1
1Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing Key Laboratory of Intelligent Diagnosis Technology and Equipment for Optic Nerve-Related Eye Diseases, Capital Medical University, Beijing, China.
Abstract:
Disruption of lipid metabolism occurs in both the retina and optic nerve following optic nerve crush (ONC); however, whether the regulation of lipid droplets (LDs) influences the survival and function of retinal ganglion cells (RGCs) remains largely elusive. Here, we identified the distribution of LDs in the retina and optic nerve of ONC mice, and A922500, a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), was applied to investigate the effect of suppressing LD biogenesis on RGC survival and visual function. The results showed that LDs were localized in Tuj1-positive cells within the retina and in IBA1-positive cells within GFAP-negative region of optic nerve following injury. A922500 significantly reduced LD accumulation and attenuated microglial density in both retina and optic nerve, but did not affect RGC survival following injury. No regenerating CTB-labeled axons were observed with A922500 monotherapy. However, combined treatment with A922500 and AAV2-CNTF enhanced axon regeneration compared to CNTF-treated alone. A922500 also significantly improved flash visual evoked potential recordings in both ONC control mice and CNTF-treated mice after injury. This study demonstrates that optic nerve crush induces LD accumulation in retinal RGC somas and in microglia at the optic nerve injury site, and reducing LDs does not preserve RGC survival but attenuates injury response, enhances CNTF-induced axon regeneration, and improves visual function.
Insights
Optic nerve crush increases lipid droplets (LDs) in retinal ganglion cells (RGCs). Inhibiting LDs did not save RGCs but improved axon regeneration and visual function when combined with CNTF.
Area of Science:
- Neuroscience
- Ophthalmology
- Metabolism
Background:
- Optic nerve crush (ONC) disrupts lipid metabolism in the retina and optic nerve.
- The role of lipid droplets (LDs) in retinal ganglion cell (RGC) survival and function after injury is unclear.
Purpose of the Study:
- To investigate LD distribution after ONC.
- To determine if inhibiting LD biogenesis affects RGC survival, axon regeneration, and visual function.
Main Methods:
- Mice underwent ONC, with or without A922500 (DGAT1 inhibitor) and/or AAV2-CNTF treatment.
- LDs were identified in retinal and optic nerve tissues.
- RGC survival, axon regeneration (CTB labeling), and visual function (flash visual evoked potentials) were assessed.
Main Results:
- ONC induced LD accumulation in RGCs and microglia.
- A922500 reduced LDs and microglial density but did not improve RGC survival.
- A922500 alone did not promote axon regeneration.
- Combined A922500 and CNTF enhanced axon regeneration and improved visual function.
Conclusions:
- ONC triggers LD accumulation in RGCs and optic nerve microglia.
- Reducing LDs attenuates the injury response and enhances functional recovery and axon regeneration, particularly with CNTF.
- Targeting LDs is a potential therapeutic strategy for optic nerve injury.
