Spatiotemporal distribution of chondroitin sulfate proteoglycans after optic nerve injury in rodents

Exp Eye Res, 2020 · DOI: 10.1016/j.exer.2019.107859 · Published: January 1, 2020

Simple Explanation

Following damage to the central nervous system (CNS), molecules called chondroitin sulfate proteoglycans (CSPGs) accumulate and limit the regeneration of injured axons. This study examines the composition of CSPGs in the optic nerve and retina after optic nerve crush (ONC) in mice and rats. The study found an increase in specific CSPGs, including aggrecan, brevican, phosphacan, neurocan, and versican, after ONC, similar to what is observed after spinal cord injury. The increase in inhibitory 4-sulfated (4S) GAG chains suggests that CSPGs in the glial scar prevent CNS axons from regrowing. These changes in CSPG composition and sulfation oppose the regrowth of damaged neurons. Therefore, this research highlights the importance of understanding CSPG dynamics for developing strategies to promote axon regeneration and functional recovery after CNS injuries.

Study Duration

Not specified

Participants

Female, 6–8 week old C57Bl/6 mice and female Sprague-Dawley rats weighing 250–275 g

Evidence Level

Not specified

Key Findings

1
Optic nerve crush (ONC) in mice and rats leads to increased expression of aggrecan, brevican, phosphacan, neurocan, and versican in the optic nerve and retina, mirroring changes seen after spinal cord injury.
2
ONC results in an elevation of inhibitory 4-sulfated (4S) glycosaminoglycan (GAG) chains, suggesting that the persistence of CSPGs in the glial scar hinders the growth of CNS axons.
3
Injured axons fail to traverse the lesion site and often terminate in areas with high CSPG deposition, indicating a potential inhibitory role of CSPGs in axonal regeneration.

Research Summary

This study investigates the spatiotemporal distribution of chondroitin sulfate proteoglycans (CSPGs) following optic nerve injury in rodents, finding similarities to CSPG changes after spinal cord injury. The research demonstrates that optic nerve crush (ONC) leads to increased expression of specific CSPG core proteins and an elevation of inhibitory 4-sulfated GAG chains in both the optic nerve and retina. The findings suggest that CSPGs play a role in obstructing axonal regeneration after optic nerve injury, highlighting the potential for therapeutic interventions targeting CSPG modification to promote functional recovery.

Practical Implications

Therapeutic Targeting of CSPGs

Modifying CSPG sulfation, particularly reducing 4-sulfation, can potentially promote axon regeneration and functional recovery after CNS injuries.

Understanding Glial Scar Composition

Further research into the specific roles of different CSPG core proteins and GAG sulfation patterns is crucial for developing targeted therapies.

Species-Specific Considerations

The timing of CSPG deposition differs slightly between mice and rats, which should be considered when designing preclinical studies and potential therapies.

Study Limitations

1
The precise duration of CSPG-mediated inhibition of axonal regeneration remains to be studied.
2
A longer-scale study would be required to elucidate whether CSPG expression declines, or whether sulfation patterns are further modified, at later times.
3
Further research is needed to fully understand the mechanisms by which CSPGs inhibit axonal growth, including the specific receptors and signaling pathways involved.

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