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Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice
Authors:Zong-Li Hu  Ni Li  Xin Wei  Li Tang  Ting-Hua Wang  Xiao-Ming Chen
Affiliation:Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China,Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China,Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China,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 and Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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/mm2) 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 (P<0.05). RGCs in BMSCs treated eyes was 625.07±89.64/mm2, significantly higher than that of no or PBS treatment (P<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 (P<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.
Keywords:optic nerve crush   retinal ganglion cells   stem cells   brain-derived neurotrophic factor   glial cell line-derived neurotrophic factor
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