Bcl-2 overexpression does not enhance in vivo axonal regeneration of retinal ganglion cells after peripheral nerve transplantation in adult mice
Bcl-2 overexpression does not enhance in vivo axonal regeneration of retinal ganglion cells after peripheral nerve transplantation in adult mice
复制标题
DOI：
10.1523/jneurosci.22-11-04468.2002
复制
发表时间：
2002-06-01
影响因子：
5.3
通讯作者：
Fukuda, Y
中科院分区：
文献类型：
--
作者：
Inoue, T;Hosokawa, M;Fukuda, Y
成年哺乳动物视神经（ON）损伤可导致视网膜神经节细胞（RGC）死亡和随后的视力丧失。视力的恢复既需要挽救被轴突切除的RGCs，也需要诱导其轴突再生。过度表达抗凋亡基因bcl-2可显著挽救axo切除的RGCs。然而，bcl-2是否影响轴突再生尚存争议。在新生的bcl-2转基因小鼠（bcl-2小鼠）中，顶叶损伤后的视束再生得到促进（Chen et al., 1997），而ON挤压后的视束再生则没有（Lodovichi et al., 2001）。这些相互矛盾的结果可能归因于顶盖和ON之间不同的环境。我们在此测试了bcl-2过表达是否通过周围神经（PN）移植物的允许环境增强成年小鼠体内RGC轴突再生。在PN移植到近端ON残端四周后，我们通过逆行标记评估存活和再生RGCs的数量。虽然与野生型（wt）小鼠相比，bcl-2小鼠的存活率显著提高，但再生率没有提高。在bcl-2和wt小鼠中，pn移植视网膜的RT97免疫染色显示一些RGC轴突在视网膜内再生，但视盘排斥。为了绕过这一排斥屏障，我们直接将PN移植物移植到部分损伤的视网膜上，并比较了这些小鼠之间的再生率。这里bcl-2小鼠的再生率也没有超过wt小鼠。这些发现表明，bcl-2过表达可以提高成体RGCs的存活，但不能提高其轴突再生，即使在一个允许的环境中也是如此。
Optic nerve (ON) injury in adult mammals causes retinal ganglion cell (RGC) death and subsequent visual loss. Recovery of vision requires both rescuing axotomized RGCs and inducing their axonal regeneration. Axotomized RGCs are significantly rescued by overexpression of bcl-2, an anti-apoptotic gene. However, whether bcl-2 affects axonal regeneration is controversial. In neonatal bcl-2 transgenic mice (bcl-2 mice), optic tract regeneration after tectal lesion was promoted (Chen et al., 1997), whereas ON regeneration after ON crush was not (Lodovichi et al., 2001). These conflicting results may be attributable to different environments between tectum and ON. We tested here whether bcl-2 overexpression enhances in vivo RGC axonal regeneration in adult mice through a permissive environment in the peripheral nerve (PN) graft. Four weeks after PN transplantation to the proximal ON stump, we assessed the number of surviving and regenerating RGCs by retrograde labeling. Although the survival rate in bcl-2 mice was significantly enhanced compared with that in wild-type (wt) mice, the regeneration rate was not enhanced. In both bcl-2 and wt mice, RT97 immunostaining of the PN-grafted retinas revealed some RGC axons regrowing intraretinally but repulsed at the optic disk. To circumvent this repulsive barrier, we directly transplanted the PN graft to the partially injured retina and compared regeneration rates between these mice. Here again the regeneration rate in bcl-2 mice did not exceed that in wt mice. These findings indicate that bcl-2 overexpression enhances survival but not axonal regeneration of adult RGCs even within a permissive environment.