| Project/Area Number |
16591759
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Kumamoto University |
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Principal Investigator |
FUKUSHIMA Mikiko Kumamoto University, University Hospital, Assistant professor, 医学部附属病院, 講師 (10284770)
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| Co-Investigator(Kenkyū-buntansha) |
KOSHIYAMA Yasuo Kumamoto University, Ophthalmology and Visual Science, Instructor, 大学院・医学薬学研究部, 助手 (40372784)
KOGA Takahisa Kumamoto University, University Hospital, Assistant professor, 医学部附属病院, 講師 (70372787)
平田 憲 熊本大学, 医学部附属病院, 講師 (60295144)
宮嶋 聖也 熊本大学, 大学院・医学薬学研究部, 助手 (10336208)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Retinal transplantation / Regenerative medicine / Stem cell / Glia / Cytokines |
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| Research Abstract |
The purpose of this study was to investigate the regulation of gliogenesis on differentiation of neural progenitor cells (NPCs) following retinal transplantation in N-methyl-D-aspartate (NMDA)-treated eyes. NPCs were prepared from telencephalic neuroepithelium of mice on embryonic day 14.5. A cell suspension was injected into the vitreous cavity in experimental eyes. Immunohistochemistry was conducted at 1, 2 or 4 weeks after transplantation of NPCs in an effort to determine the survival and differentiation of transplanted NPCs.
Examination of retinal sections revealed that transplanted NPCs could survive for at least 4 weeks in NMDA-treated retinas. Immunohistochemical studies revealed that the differentiation of transplanted NPCs with a preference for the glial lineage. Following transplantation of NPCs isolated from glycoprotein (gp) 130-null (-/-) mice into NMDA-treated retinas, the mean percentage of GFAP-positive cells was significantly lower than that in NPCs isolated from wild-type mice. The expression of ciliary neurotrophic factor (CTNF), which induce glial differentiation of the progenitors, was significantly inhibited in NMDA-damage eye with nonsteroidal anti-inflammatory drug (NSAID) treatments. Also, our results showed inhibitory effects of NSAID against predominant glial differentiation of NPCs in the NMDA-damaged retinas. In NPCs transduced with retrovirus encoding Ngn1 gene, neuronal differentiation was hardly observed in NMDA damaged retinas. It was not in accordance with the cell culture experiments.
Preferential differentiation of NPCs into the glial lineage is induced through gp130 signaling in NMDA-treated eyes. It has been suggested that the regulation of gp130 signaling have beneficial effects on the retinal transplantation and subsequent regulation of NPCs for neuronal differentiation.
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