Sustained effects of gene-activated matrices after CNS injury.
We show that when gene-activated matrices (GAM) are placed between the proximal and distal stumps of severed rat optic nerves, DNA is retained within the GAM, promoting sustained transgene expression in the optic nerve, in the GAM itself, and, more importantly, in axotomized retinal ganglion cells (RGC). Plasmids that encode basic fibroblast growth factor (FGF2), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) promote sustained survival of RGC for over 3 months after the initial injury. These findings suggest that immobilized DNA implanted into a CNS lesion will be delivered by axon terminal uptake and retrograde transport to axotomized neurons. GAM may therefore be a useful agent for promoting sustained neuron survival and axon regeneration. Whether further optimization of the matrices, plasmids, promoters, and genes present in the GAM will promote even more survival or, alternatively, axon regeneration remains to be determined.
Berry
M
M
Centre for Neuroscience, Neural Damage and Repair, GKT (Guy's Campus), Hodgkin Building, London Bridge, London, SE1 1UL, United Kingdom.
Gonzalez
A M
AM
Clarke
W
W
Greenlees
L
L
Barrett
L
L
Tsang
W
W
Seymour
L
L
Bonadio
J
J
Logan
A
A
Baird
A
A
D000818:Animals; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D006224:Cricetinae; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D007668:Kidney / Q000166:cytology; D020933:Neurotrophin 3 / Q000235:genetics; D009900:Optic Nerve / Q000166:cytology / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000628:therapy*; D010957:Plasmids; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology; D014162:Transfection / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D016222:Fibroblast Growth Factor 2