TY - JOUR
T1 - Sustained effects of gene-activated matrices after CNS injury
AU - Berry, Martin
AU - Gonzalez, Ana
AU - Leadbeater, Wendy
AU - Greenlees, L
AU - Barrett, Lee
AU - Tsang, W
AU - Seymour, Leonard
AU - Bonadio, J
AU - Logan, Ann
AU - Baird, Andrew
PY - 2001/4/1
Y1 - 2001/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035003588&partnerID=8YFLogxK
U2 - 10.1006/mcne.2001.0975
DO - 10.1006/mcne.2001.0975
M3 - Article
C2 - 11312606
VL - 17
SP - 706
EP - 716
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
ER -