Innovative Optic Tract Repair Model Enhances CNS Recovery

A research team led by Prof. Liu Kai at the Hong Kong University of Science and Technology (HKUST) has developed an innovative model to investigate optic tract injuries and the potential for axonal rewiring in the central nervous system (CNS). This groundbreaking study, titled "Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement," was published in Nature Communications in March 2025.

Introduction to the CNS Repair Challenge

The adult mammalian CNS exhibits a notoriously low capacity for self-repair following injury, primarily due to the inability of axons to regenerate and form functional connections with their target neurons. Traditional research has primarily concentrated on enhancing axonal regeneration, while the mechanisms for functional circuit reconstruction have remained largely unexplored.

The Pre-Olivary Pretectal Nucleus (OPN) Optic Tract Injury Model

To address these research gaps, the team introduced the intracranial pre-OPN optic tract injury (OTI) model. This innovative approach involves:

• Microsurgical Technique: Application of mechanical pressure between the lateral geniculate nucleus (LGN) and the OPN, effectively injuring retinal ganglion cell (RGC) axons.
• Simplified Surgery: Avoids cortical tissue removal, thus lowering surgical complexity and risk.
• Target Proximity: The injury site is in close proximity to the target nucleus (OPN), which enhances targeted axonal regeneration studies.
• Functional Evaluation: Utilization of the pupillary light reflex (PLR) as a quantitative measure for functional recovery.
• Survival Assurance: High rates of RGC survival post-injury, facilitating long-term observation of regeneration.

Key Findings and Mechanisms of Recovery

The study revealed that knocking out the Pten/Socs3 genes in RGCs while expressing CNTF markedly enhances axonal regeneration to the OPN and facilitates the reformation of functional synapses. Key findings include:

For further insights, the research team suggested a dual-intervention strategy of axonal regeneration and synaptic enhancement. Specific strategies included:

• Knockdown of Lipin1: This gene manipulation, alongside Pten/Socs3 knockout and CNTF expression, resulted in accelerated axonal regeneration, significantly reducing PLR recovery time from 6 months to a remarkable 3 months.
• Overexpression of Melanopsin: Enhanced RGC photosensitivity, optimizing synaptic signal transmission and improving functional outcomes considerably.

Discussion and Implications for Future Research

The pre-OPN OTI model serves as a pivotal tool in CNS repair research by clarifying the intricate roles of specific neuronal subtypes in functional circuit reconstruction. Furthermore, it confirms the potential application of dual-intervention strategies to enhance recovery from neural injuries and neurodegenerative diseases.

“This innovative research deepens our understanding of CNS mechanisms and offers new avenues for developing precision therapies targeting neurological conditions.” – Prof. Liu Kai

Conclusion

The ground-breaking findings from this study provide a framework for future investigations into CNS injury repair mechanisms. By focusing on both axonal regeneration and the restoration of synaptic functions, researchers now have a clearer path toward developing effective treatment strategies for CNS-related injuries.

References

[1] Zhang, X., Liu, K., et al. (2025). Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement. Nature Communications.

[2] DOI: 10.1038/s41467-025-57445-x

[3] Access the research study here: Medical Xpress