Development of new method for optic nerve regeneration-a combined approach of the peripheral nerve transplant and intraocular injection of neurotrophins.

在哺乳动物中，视网膜神经节细胞在轴突切断后不能再生轴突，其胞体遭受逆行性细胞死亡。然而，对于周围神经移植物，视网膜神经节细胞的轴突可以通过移植的神经再生。到目前为止，再生轴突的数量据报道不到总视神经纤维的5%。为了增强轴突切断的视网膜神经节细胞的细胞存活和轴突再生，我们试图研究眼内注射各种神经营养素与周围神经移植物相结合对细胞存活和轴突再生的影响。结果表明：（1）眼内注射脑源性神经营养因子（BDNF）可促进视网膜内视网膜神经节细胞轴突的再生，但不能使这些轴突穿透视神经，提示视盘周围存在一些非允许性分子。(2)因此，眼内注射BDNF与周围神经移植物的组合不能有效地提高具有再生轴突的神经节细胞进入移植物的数量。(3)低亲和力神经生长因子受体（LNGFR）和一些neurotophin受体mRNA定位于视网膜神经节细胞亚群。(4)用我们最近分离的单克隆抗体C38进行免疫染色，可以区分没有再生轴突的存活视网膜神经节细胞和再生轴突的视网膜神经节细胞。

In mammals, retinal ganglion cells can not regenerate their axons after axotomy and their somas suffer from retrograde cell death. With peripheral nerve graft, however, axons of retinal ganglion cells can regrow through the grafted nerve. So far the number of regrowing axons is reported to be less than 5% of the total optic nerve fibers. To enhance cell servival and axonal regeneration of axotomized retinal ganglion cells, we tried to examine the effects of intraocular injections of various neurotrophins on cell survival and axonal regeneration in combination with the peripheral nerve graft. We made the following findings : (1) Intraocular injection of brain derived neurotrophic factor (BDNF) promotes axonal regrowth of retinal ganglion cells withih the retina but it is not effective for these intraretinal axons to penetrate into the optic nerve, suggesting existence of some non-permissive molecules around the optic disc. (2) Thus, the intraocular injections of BDNF in combination with the peripheral nerve graft was not effective to improve the number of ganglion cells with regenerated axons into the graft. (3) Low affinity NGF receptor (LNGFR) and some neurotophin receptor mRNAs were localized in subpopulations of retinal ganglion cells. (4) The surviving retinal ganglion cells without regenerating axons could be distinguished from those with regenerated axons by immunostaining with the monoclonal antibody C38 that we have recently isolated.