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Rescue of retinal ganglion cells from axotomy-induced apoptosis through TRK oncogene transfer
E Garcia Valenzuela1, S C Sharma
1Department of Cell Biology, New York Medical College, Valhalla 10595, USA.
Abstract:
Following axonal injury, central neurons die through programmed cell death. Modification of intracellular mechanisms through specific gene transfer might provide a mechanism for survival. Here we present rescue of rat retinal ganglion cells (RGCs) through gene transfer of TRK oncogenes. Administration of plasmid DNA at the optic axon terminals in the superior colliculus results in retrograde transport to their soma and significant expression of the exogenous DNA. Using this approach for transfection, a TRK oncogene containing plasmid was introduced in RGCs. Three days after plasmid injection, optic nerves were transected. TRK oncogene transfection induced extended survival of the axotomized neurons, lasting over 10 days. Gene delivery to specific cell types is an initial step in the development of therapeutic strategies for regeneration of the damaged nervous system.
Insights
Gene transfer of TRK oncogenes rescued rat retinal ganglion cells (RGCs) after axonal injury. This neuroprotective strategy shows promise for central nervous system regeneration therapies.
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Central nervous system neurons undergo programmed cell death after axonal injury.
- Gene transfer offers a potential strategy to modify intracellular mechanisms for neuronal survival.
Purpose of the Study:
- To investigate the neuroprotective effects of TRK oncogene gene transfer in rat retinal ganglion cells (RGCs) following axonal injury.
Main Methods:
- Plasmid DNA encoding a TRK oncogene was administered to optic axon terminals in the superior colliculus for retrograde transport.
- Rat RGCs were transfected with the TRK oncogene plasmid.
- Optic nerves were transected three days after plasmid injection.
Main Results:
- TRK oncogene transfection led to significant expression of the exogenous DNA in RGCs.
- Axotomized RGCs exhibited extended survival, lasting over 10 days post-transection.
- This demonstrates successful gene delivery and neuroprotection in damaged neurons.
Conclusions:
- TRK oncogene gene transfer can induce extended survival of axotomized RGCs.
- Gene delivery to specific cell types is a viable initial step for developing therapeutic strategies for nervous system regeneration.
- This approach holds potential for treating central nervous system damage.