Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants |
|Research Institution||KYUSHU UNIVERSITY |
ISHIBASHI Tatsuro Kyushu University, Department of Ophthalmology, Professor, 大学院医学研究院, 教授 (30150428)
SUEISHI Katuso Kyushu University, Department of Pathology, Professor, 大学院医学研究院, 教授 (70108710)
YONEMITSU Yoshikazu Kyushu University, Graduate School of Medical Sciences, Professor, 大学院医学研究院, 特任教授 (40315065)
SONODA Ko-Hei Kyushu University, Department of Ophthalmology, Research Associate, 大学院医学研究院, 助手 (10294943)
GOTO Yoshinobu International University of Health and Welfare, Faculty of Rehabilitation, Associate Professor, リハビリテーション学部, 助教授 (30336028)
IKEDA Yasuhiro Kyushu University, University Hospital, Research Associate, 大学病院, 助手 (20380389)
|Project Period (FY)
2003 – 2005
Completed (Fiscal Year 2005)
|Budget Amount *help
¥46,540,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥10,740,000)
Fiscal Year 2005: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2004: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2003: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
|Keywords||Gene therapy / Retinal degeneration / Neural progenitor cells / SIV vector / PEDF / FGF-2 / Age-related macular degeneration / hFGF-2 / RCSラット / rdsマウス / PEDF|
1. The assessment of the efficacy of gene therapy for the animal models of retinal degeneration
1) Development of new gene therapy technology
We developed the new SIV (simian immunodeficiency virus) vectors carrying hFGF-2 or both hPEDF and hFGF-2 (SIV-FGF-2 or SIV-dual). Moreover, we developed the system for large-scale production of SIV-hPEDF with the aim of the clinical trail.
2) We showed the synergistic therapeutic effect using SIV-hPEDF and SIV-hFGF-2 for two animal models of retinal degeneration (RCS rats and rds mice)
2. The establishment of new gene therapy strategy by use of neural progenitor cells
1) Development of the culture method to isolate neural progenitor cells from ciliary body of the eye
We identified a new and divergent mechanism (a reprogramming system) underlying the neural differentiation of ciliary body-derived cells via sphere formation. The nestin-negative epithelial-like cells from ciliary body came to express nestin.
2) We demonstrated the efficient gene transfer to neural progenitor cells from ciliary body of the eye via SIV vector
1) We evaluated the ability of our 3rd generation SIV vectors to transfer genes into nonhuman primate retinas.
2) We suggested the possibility that VEGF-C and VEGF-D expression in RPE modify the ocular angiogenesis, such as age-related macular degeneration (AMD) as angiogenic stimulators.