Regeneration and repair in the rodent visual system: an in vivo gene therapy and neural transplantation study

Funded Activity Summary

In the adult human central nervous system (CNS), traumatic injury, stroke, or loss of nerve cells due to degenerative disease all result in long-term and severe functional impairments. The personal, social and economic costs associated with these neurological problems are massive. In the proposed work, gene therapy and transplant techniques will be used to develop new cooperative strategies for neural repair. The aims are to protect and-or replace damaged nerve cells (neurons) and promote the long-distance regrowth of their processes (axons). The ultimate goal is to improve the treatment of human CNS injury and disease, leading to better functional recovery. We will use the visual system as our experimental CNS model. Viruses are novel tools that can be used for the introduction of foreign genes into cells. We will use modifed, non-harmful viral vectors to genetically alter retinal neurons. We will incorporate extra copies of known neuroprotective and-or growth-promting genes into retinal cells and analyze whether these genetically engineered neurons possess a greater ability to survive and regenerate their axons after injury. We will combine this approach with the transplantation of peripheral nerve bridges which are known to boost the regrowth of CNS axons. We will also test the effects of viral transfer of genes into retinal neurons in transgenic mice that have already been given an 'extra dose' of a neuroprotective gene. We will determine if different genes cooperate together to produce a synergistic therapeutic effect after CNS injury. The above studies focus on regeneration in what are essentially acute injury models. We are also interested in the restoration of circuitry in chronic situations, where the damage occured some time previously and neurons have already been lost. We will therefore graft neural precursor cells into the rat eye in an attempt to replace endogenous retinal neurons that are dying or have been lost due to injury.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $426,000.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical infection agents (incl. prions)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

CNS repair after injury | adeno-associated virus | axon regeneration | gene therapy | neuroprotection | neurotrauma | retina | retinal degeneration | transplantation

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