Fagiolini M, Caleo M, Strettoi E, Maffei L
Scuola Normale Superiore and Istituto di Neurofisiologia del Consiglio Nazionale delle Ricerche, 56127 Pisa, Italy.
J Neurosci. 1997 Sep 15;17(18):7045-52. doi: 10.1523/JNEUROSCI.17-18-07045.1997.
Optic nerve section in the newborn rat results in a rapid apoptotic degeneration of most axotomized retinal ganglion cells (RGCs). This massive process of neuronal death has been ascribed mainly to the interruption of a trophic factor supply from target structures rather than to the axonal damage per se. To distinguish between these two possibilities, we induced a reversible axonal transport blockade in the developing optic nerve by topical application of a local anesthetic (lidocaine). Light and electron microscopy showed no alterations in the fine structure of treated optic nerves. Retinae of treated and control rats were stained with cresyl violet and examined at different times after surgery. We found that axonal transport blockade induced only a limited number of pyknotic RGCs. Degeneration of these cells was completely prevented by inhibiting protein synthesis during lidocaine application. We conclude that the rapid degeneration of RGCs after axotomy can be ascribed only partly to the loss of retrogradely transported trophic factors.
新生大鼠的视神经切断会导致大多数轴突被切断的视网膜神经节细胞(RGCs)迅速发生凋亡性退变。这种大规模的神经元死亡过程主要归因于来自靶结构的营养因子供应中断,而非轴突损伤本身。为区分这两种可能性,我们通过局部应用局部麻醉剂(利多卡因)诱导发育中的视神经发生可逆性轴突运输阻断。光镜和电镜检查显示,处理后的视神经精细结构无改变。对处理组和对照组大鼠的视网膜进行甲酚紫染色,并在术后不同时间进行检查。我们发现,轴突运输阻断仅诱导了有限数量的固缩RGCs。在应用利多卡因期间抑制蛋白质合成可完全防止这些细胞的退变。我们得出结论,轴突切断后RGCs的快速退变仅部分归因于逆行运输的营养因子的丧失。