| Project/Area Number |
15591851
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
HARUTA Masatoshi Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (90359802)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Masayo Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (80252443)
KAGEYAMA Ryoichiro Kyoto University, Institute for Virus Research, Professor, ウィルス研究所, 教授 (80224369)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Retinitis pigmentosa / Age-related macular degeneration / Iris / Crx homeobox gene / Photoreceptor cells / Embryonic stem cells / Retinal pigment epithelium / Retinal transplantation / 分化誘導 / Crx / ホメオボックス遺伝子 / 過分極 / 視細胞変性疾患 / 網膜色素上皮 / 網膜再生 / RCSラット / 加齢性黄斑変性 |
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| Research Abstract |
Many ocular diseases, such as retinitis pigmentosa and age-related macular degeneration, reflect damage to specific retinal cell types. Preliminary results of animal studies suggest that these retinal degenerative diseases may be treatable by transplantation of healthy fetal photoreceptor or retinal pigment epithelial cells. However, obtaining suitable donor cells remains a problem for their clinical application.
When the Crx homeobox gene was induced to the iris-derived cells of adult rats and then transferred to an environment that promotes retinal cell differentiation, these iris-derived cells showed several photoreceptor-specific markets. Intracellular recordings were made from these Crx-transduced iris-derived cells and light-induced membrane hyperpolarization was observed to light-stimulus. They also showed capacity to integrate and survive under co-culture condition with embryonic retinal explant culture. Since the iris tissue can be obtained easily and safely with peripheral iri
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dectomy, these iris-derived cells may constitute a potential source of autologous photoreceptor transplantation in patients with retinal degenerative diseases.
When the primate embryonic stem cells were co-cultured with PA6 stromal cells, the pigment epithelial cells can be reproducibly differentiated from primate embryonic stem cells. The purified and expanded epithelial cells exhibited hexagonal shape and expressed several specific markers for the retinal pigment epithelial cells. Transmission electron microscopy confirmed that they featured extensive microvilli and were able to phagocytose, which are necessary for photoreceptor survival. When transplanted into the subretinal space of dystrophic RCS rats, the photoreceptor cells directly over the grafted cells were rescued from degeneration. The behavioral assessment of transplanted recipients showed that pigment epithelial cells differentiated from embryonic stem cells could preserve a significant level of visual function when transplanted. The remarkable developmental potential and replicative capability of embryonic stem cells would provide an unlimited source of retinal pigment epithelial cells that could be used for retinal cell transplantation therapy. Less
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