TrkB gene transfer protects retinal ganglion cells from axotomy-induced death in vivo

被引:223
作者
Cheng, L
Sapieha, P
Kittlerová, P
Hauswirth, WW
Di Polo, A
机构
[1] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H3T 1J4, Canada
[2] McGill Univ, Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada
[3] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA
[4] Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA
关键词
retinal ganglion cells; axotomy; gene transfer; TrkB; MAP kinase; cell survival;
D O I
10.1523/JNEUROSCI.22-10-03977.2002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Injury-induced downregulation of neurotrophin receptors may limit the response of neurons to trophic factors, compromising their ability to survive. We tested this hypothesis in a model of CNS injury: retinal ganglion cell (RGC) death after transection of the adult rat optic nerve. TrkB mRNA rapidly decreased in axotomized RGCs to similar to50% of the level in intact retinas. TrkB gene transfer into RGCs combined with exogenous BDNF administration markedly increased neuronal survival: 76% of RGCs remained alive at 2 weeks after axotomy, a time when >90% of these neurons are lost without treatment. Activation of mitogen-activated protein kinase, but not phosphatidylinositol-3 kinase, was required for TrkB-induced survival. These data provide proof-of-principle that enhancing the capacity of injured neurons to respond to trophic factors can be an effective neuroprotective strategy in the adult CNS.
引用
收藏
页码:3977 / 3986
页数:10
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