PROTECTION FROM DEATH OF AXOTOMIZED RETINAL GANGLION CELLS AND PROMOTION OF THEIR AXONAL REGENERATION

哺乳动物视网膜神经节细胞（RGC）的轴突再生为移植的周围神经节段，但再生的RGC的数量平均为2%。它们太小而不能用于受损视力的功能恢复，或引导干细胞衍生的RGC的轴突进入中央视觉区域。因此，应该开发增加数量的方法。我们测试了几种保护轴突切断的RGC死亡的药物，因为轴突切断的RGC的存活是轴突再生的首要条件。并获得了轴突再生率.为了建立一种促进RGC存活的方法，检测了切断轴突的RGC的存活曲线。β细胞在第3天至第7天之间迅速退化，而α细胞直到第14天才缓慢退化。快速期β细胞的死亡是由于细胞凋亡，并且能够用半胱天冬酶抑制剂预防。2.我们玻璃体内注射药物，据报道，以防止啮齿动物RGC死亡后轴突切断。BDNF、CNTF和forskolin的组合促进猫RGCs的存活，尤其是β细胞。抗青光眼药物尼普拉洛（NP）在10 μ mol. 3时可保护受损的RGC免于死亡<-7>。再生轴突的延长率估计在猫RGCs。整个RGCs的平均速率估计为1.1 mm/d。α细胞的增殖速率最快，为1.4mm/d，β细胞为1.1mm/d，其它细胞为1.0mm/d。阿尔法细胞的最高比率反映了它们再生轴突的能力更强。这些值用作促进轴突伸长的方法时的对照值.联合应用BDNF、CNTF和forskolin可增加再生RGCs的数量，但不能增加轴突再生细胞的轴突再生。10 μ mol的NP<-7>使再生的RGCs的数量增加到3-4倍，并将20 mm轴突伸长的时间缩短7天。

Retinal ganglion cells (RGCs) of mammals regenerate their axons into a grafted peripheral nerve segment, but numbers of regenerated RGCs are 2% in average. They are too small to intend functional recovery of impaired vision, or to guide axons of stem cell-derived RGCs into the central visual areas. Therefore, methods increasing the numbers should be developed. We tested several drugs which protect death of axotomized RGCs since survival of axotomized RGCs is the first requisite for axonal regeneration. We also obtained rate of axonal regeneration.1. To develop a method promoting RGC survival, survival curve of axotomized RGCs were examined. Beta cells degenerate rapidly between day 3 to 7, while alpha cells did slowly until day 14. Death of beta cells in the rapid phase was due to apoptosis, and was able to be prevented with a caspase inhibitor. 2. We intravitrealy injected drugs which are reported to prevent rodent RGC death after axotomy. Combination of BDNF, CNTF and forskolin facilitated survival of cat RGCs, especially beta cells. Nipradilol (NP), an anti-glaucoma drug, protects injured RGCs from death at 10^<-7> mol.3. Rates of prolongation of regenerated axons were estimated in cat RGCs. The average rate of whole RGCs was estimated as 1.1 mm/d. Alpha cells had the most rapid rate as 1.4 mm/d, compared with beta cells' (1.1 mm/d) and other cells' (1.0 mm/d). The highest rate of alpha cells reflects their greater ability to regenerate axons. The values are used as control values when a method to facilitate axonal elongation.4. Combination of BDNF, CNTF and forskolin increased numbers of regenerated RGCs, but did not increase axonal regeneration of cells which survived axotomy without axonal regeneration. NP at 10^<-7> mol increased numbers of regenerated RGCs into 3-4 fold, and shortened time for 20 mm axonal elongation by 7 days.