2005 Fiscal Year Final Research Report Summary
Transplantation for retinal diseases
| Project/Area Number |
14370553
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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 |
ABE Toshiaki Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90191858)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Yuko Tohoku University Hospital, Lecture, 病院・講師 (70302130)
TOMITA Hiroshi Tohoku University, Graduate School of Medicine, Research associate, 大学院・医学系研究科, 助手 (40302088)
SATO Hajime Tohoku University Hospital, Research associate, 病院・助手 (10312571)
YAMATO Masayuki Tokyo Women's Medical University, Lecture, 医学部, 講師 (40267117)
OKANO Mitsuo Tokyo Women's Medical University, Professor, 医学部, 教授 (00130237)
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| Project Period (FY) |
2002 – 2005
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| Keywords | retinal pigment epithelium / iris pigment epithelium / brain derived-neurotrophic factor / adeno-associated virus / cell transplantation / TrkB |
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| Research Abstract |
We report a subretinal iris pigment epithelial cell (IPE) transplantation with safely. When these cells were genetically engineered that expressing neurotrophic factors, the transplantation rescued the photoreceptor cells from phototoxicity. We used adeno-associate virus (AAV2) for delivering neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) to the transplanted cells. If we used more than 1x107 capsides/ml AAV-BDNF for transfection, statistically significant photoreceptor protection was observed in the AAV-BDNF-IPE transplantation from phototoxicity. However, the rescue effect was not dose-dependent. Then, we examined the BDNF receptor TrkB expression, because the receptor may control the effect of BDNF. So far many isoforms of TrkB have reported and we examined two of the major isoforms of TrkB ; TrkB-FL which has tyrosine kinase activity in the cell and TrkB-T1 which has not. These isoforms showed not always completely same expression by immunohistochemistry. TrkB-FL was expressed mainly on nerve fiber layer, ganglion cells layer, and inner nuclear layer (INL), conversely TrkB-T1 was on INL and RPE. Both isoforms were not expressed in ONL and photoreceptor layer. From the results of double immunostaining with S100β, These isforms were expressed on Muller cells. Further these isoforms were expressed in the retina not only spatially but also temporally different way, although the expression was enhanced by the AAV-BDNF-IPE transplantation. When we performed in situ hybridization, same expression pattern were also confirmed. siRNA experiments showed significant less photoreceptor protection when we injected siRNA of TrkB-T1. When we examined differential gene expression by DNA microarray of Muller cell line, rMC-1 between BDNF stimulated and non-stimulated, neurotrophic factors that were so far reported were not many expressed. Another mechanism such as scavenging the ions in the surrounding circumstances may be important.
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Research Products
(43 results)
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[Journal Article] Hypothermia Protects Cultured Human Retinal Pigment Epithelial Cells against Trypan Blue Toxicity.2006
Author(s)
Kunikata H, Tomita, H, Murata H, Sagara Y, Sato H, Wada Y, Fuse N, Nakagawa Y, Abe T, Tamai M.
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Journal Title
Ophthalmologica. 220
Pages: 114-117
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A case of Fukuyama-type congenital muscular dystrophy with a very mild mental deficit.2006
Author(s)
Hino-Fukuyo N, Haginoya K, Hayashi YK, Nishino I, Murakami T, Nonaka I, Togashi K, Tanaka S, Takayanagi M, Yokoyama H, Sakamoto O, Abe T, Toda T, Iinuma K.
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Journal Title
Neuromuscul Disord. 16
Pages: 274-276
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Recombinant AAV-transduced Iris Pigment Epithelial Cells Transplantation May transfer Vector to Native RPE but Suppress Syntemic Dissemination2006
Author(s)
Yoshioka Y, Abe T, Wakusawa R, Moriya T, Mochizuki S, Saigo Y, Saito T, Murata Y, Tokita Y, Iseya T, Sugano E, Tomita H, Sagara Y, Tamai M
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Journal Title
Invest Ophthalmol Vis Sci 47
Pages: 745-752
Description
「研究成果報告書概要(欧文)」より
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