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脑源性神经营养因子和胶质细胞源性神经营养因子对小鼠视神经挤压伤后玻璃体内移植间充质干细胞的神经保护作用

Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice.

作者信息

Hu Zong-Li, Li Ni, Wei Xin, Tang Li, Wang Ting-Hua, Chen Xiao-Ming

机构信息

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

出版信息

Int J Ophthalmol. 2017 Jan 18;10(1):35-42. doi: 10.18240/ijo.2017.01.06. eCollection 2017.

Abstract

AIM

To assess the neuro-protective effect of bone marrow mesenchymal stem cells (BMSCs) on retinal ganglion cells (RGCs) following optic nerve crush in mice.

METHODS

C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs (BIM), and GDNF-interference BMSCs (GIM) following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively.

RESULTS

The density (cell number/mm) of RGCs was 410.77±56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39±195.97 in the normal control (<0.05). RGCs in BMSCs treated eyes was 625.07±89.64/mm, significantly higher than that of no or PBS treatment (<0.05). While RGCs was even less in the retina with intravitreal injection of BIM (354.07+39.77) and GIM (326.67+33.37) than that without treatment (<0.05). BMSCs injection improved the internal BDNF expression in retinas.

CONCLUSION

Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs.

摘要

目的

评估骨髓间充质干细胞(BMSCs)对小鼠视神经挤压伤后视网膜神经节细胞(RGCs)的神经保护作用。

方法

视神经挤压伤后,分别对C56BL/6J小鼠玻璃体内注射PBS、BMSCs、BDNF干扰BMSCs(BIM)和GDNF干扰BMSCs(GIM)。通过视网膜铺片和冰冻切片确定存活RGCs的数量,同时分别用q-PCR或ELISA检测特定的mRNA或蛋白质。

结果

视神经挤压伤后21天未进行任何处理的小鼠视网膜中RGCs的密度(细胞数/mm)为410.77±56.70,而正常对照组为1351.39±195.97(P<0.05)。BMSCs处理组小鼠视网膜中RGCs为625.07±89.64/mm,显著高于未处理组或PBS处理组(P<0.05)。而玻璃体内注射BIM(354.07+39.77)和GIM(326.67+33.37)的视网膜中RGCs甚至比未处理组更少(P<0.05)。注射BMSCs可提高视网膜内BDNF的表达。

结论

视神经挤压伤导致RGCs大量丢失,玻璃体内移植BMSCs在一定程度上保护RGCs免于死亡。BMSCs的作用及视网膜中BDNF的水平均与BMSCs中BDNF和GDNF的表达有关。

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