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

开发视神经再生新方法——周围神经移植和神经营养因子眼内注射相结合的方法。

基本信息

批准号：
06557091
负责人：
FUKUDA Yutaka
金额：
$ 8.32万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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.

在哺乳动物中，视网膜神经节细胞在轴突切除后不能再生其轴突，其胞体遭受逆行细胞死亡。周围神经移植后，视网膜神经节细胞轴突可通过移植神经再生。据报道，到目前为止，再生轴突的数量还不到视神经纤维总数的5%。为了提高经轴突切除的视网膜神经节细胞的细胞存活率和轴突再生能力，我们尝试观察眼内注射各种神经营养物质联合周围神经移植物对细胞存活和轴突再生的影响。研究结果如下：(1)眼内注射脑源性神经营养因子（BDNF）可促进视网膜神经节细胞随视网膜的轴突再生，但对这些视网膜内轴突渗透到视神经没有作用，提示视盘周围存在一些非允许分子。(2)因此，眼内注射BDNF联合周围神经移植物并不能有效提高移植物中具有再生轴突的神经节细胞的数量。(3)低亲和力NGF受体（lnfr）和部分神经啡肽受体mrna存在于视网膜神经节细胞亚群中。(4)用我们最近分离的单克隆抗体C38进行免疫染色，可以区分未再生轴突的视网膜神经节细胞和轴突再生的视网膜神经节细胞。