| Project/Area Number |
15390524
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tohoku University |
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Principal Investigator |
TAMAI Makoto Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90004720)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Yoichi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10282063)
FUSE Nobuo Tohoku University, Hospital, Lecturer, 病院・講師 (10302134)
SATO Hajime Tohoku University, Hospital, Research Associate, 病院・助手 (10312571)
TOMITA Hiroshi Tohoku University, Biomedical Engineering Research Organization, Associate Professor, 先進医工学研究機構, 助教授 (40302088)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2004: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2003: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | age-related macular degeneration / Retinitis pigmentosa / gene transfer / Cell transplantation / Iris pigment epithelium / Adeno-associate virus / 虹彩色素上皮 / ウイルスベクター |
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| Research Abstract |
We have been trying a clinical approach to the patients with AMD by transplantation of autologous cultured IPE cells. More than 80% of the patients showed an improvement of visual acuity after the transplantation. However the best visual acuity in these patients was still far from sufficient effect. These reports suggested that there is a limitation in the use of autologous IPE cells for transplantation. We investigated the stable and safety gene transduction to IPE cells. The purpose of this study is to demonstrate the effect of the neurotrophic factors-transduced cells and safety of vector to use gene transfer. The stability of transgene expression in the retina was needed for gene therapy. One of methods to transduce a gene into relevant cells is to use virus vectors. Now we can use various type of virus vectors. The recombinant adeno-associated virus (rAAV) has proven to be an efficient and effective vector. We studied the transduction efficiency to IPE cells by using 5 types of AAV serotypes. These results revealed that serotype 2 (rAAV2) is the most effective vector for gene therapy in IPE cells. But the trasduction efficiency was less than 20%. To improve this problem, we studied the manner of virus infection and revealed that the pre-treatment with tyrphostin-1 (epidermal growth factor receptor tyrosine kinase inhibitor) led to increase of AAV2-transduction. The neuroprotective effect of AAV BDNF transduced IPE cells (BDNF-IPE) on the retinal ganglion cells (RGCs) were assessed. In vitro, BDNF deprivation RGC death was significantly suppressed by HUSB-Tyr treated-BDNF-IPE. In vivo model of photoreceptor degeneration caused by continuous light exposure, transplantation of HUSB-Tyr-treated-BDNF-IPE inhibited photoreceptor degeneration.
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