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Restoration of Visual Function by Enhancing Conduction in Regenerated Axons
Fengfeng Bei1, Henry Hing Cheong Lee1, Xuefeng Liu1
1F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Cell
|January 16, 2016
Summary
Strategies promoting central nervous system axon regeneration can restore functional synapses but not vision. Enhancing myelination and action potential conduction in regenerated retinal axons is crucial for visual recovery after injury.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Ophthalmology
Background:
- Mammalian central nervous system (CNS) repair strategies promote axon regrowth but functional recovery remains limited.
- It is unclear if regenerated axons form functional synapses and restore behavior after injury.
Purpose of the Study:
- To investigate if promoting axon regeneration and synapse formation in the CNS leads to functional recovery.
- To identify the barriers to functional recovery after retinal axon injury and explore potential therapeutic interventions.
Main Methods:
- Genetic manipulation (PTEN/SOCS3 co-deletion, OPN/IGF1/CNTF co-overexpression) in juvenile and adult mice.
- Assessment of retinal axon regrowth, synapse formation in the superior colliculus (SC), and visual function.
- Analysis of action potential conduction in regenerated axons and the role of myelination.
Main Results:
- Co-deletion of PTEN/SOCS3 or co-overexpression of OPN/IGF1/CNTF induced retinal axon regrowth and synapse formation in the SC.
- Regenerated axons failed to conduct action potentials due to lack of myelination, hindering visual function recovery.
- Administration of voltage-gated potassium channel blockers restored conduction and improved visual acuity.
Conclusions:
- Axon regeneration and synapse formation alone are insufficient for functional recovery after CNS injury.
- Myelination and action potential conduction are critical barriers to functional recovery in regenerated axons.
- Combined strategies enhancing both regeneration and conduction offer a promising therapeutic approach for visual restoration after retinal axon injury.
