Rescue of retinal ganglion cells from axotomy-induced apoptosis through TRK oncogene transfer.
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.
Garcia Valenzuela
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Department of Cell Biology, New York Medical College, Valhalla 10595, USA.
Sharma
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SC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019771:Axotomy; D002470:Cell Survival / Q000502:physiology; D018014:Gene Transfer Techniques; D008845:Microinjections; D009857:Oncogenes / Q000502:physiology; D009900:Optic Nerve / Q000737:chemistry / Q000166:cytology / Q000601:surgery; D010957:Plasmids; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D013477:Superior Colliculi / Q000737:chemistry / Q000166:cytology
D020794:Receptor Protein-Tyrosine Kinases