2007 Fiscal Year Final Research Report Summary
New Treatment for Age-related Macular Degeneration Antiangiogenic Thereapy using Nanotechnology and Retianl Regenerative Therapy
| Project/Area Number |
18390465
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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 | The University of Tokyo |
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Principal Investigator |
TAMAKI Yasuhiro The University of Tokyo, Tokyo University Hospital, Associate professor (20217178)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGI Yasuo The University of Tokyo, Tokyo University Hospital, lecturer (90376442)
KATAOKA Kazunori The University of Tokyo, Department of Materials Engineering, Graduate School of Engineering, Professor (00130245)
FURUKAWA Takahisa Osaka Bioscience Institute, Department of Developmental Biology, Head (50260609)
KONDO Mineo The University of Tokyo, Nagoya University Hospital, Associate professor (80303642)
TAHARA Hideaki The Institute of Medical Science, Department of Surgery and Bioengineering, 教授 (70322071)
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| Project Period (FY) |
2006 – 2007
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| Keywords | age-related macular degeneration / photodynamic therapy / polyion complex micelle / choroidal neovascularization / VEGFR2 / immunotherapy / genome microarray chips |
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| Research Abstract |
Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Even with the recent advent of several treatment options, treatment of exudative AMD, characterized by choroidal neovascularization (CNV), remains difficult. We investigated new management of AMD.
We present an effective photodynamic therapy (PDT) for AMD employing a new dendritic photosensitizer encapsulated by a polymeric micelle formulation. With its highly selective accumulation on CNV lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity. Our results will provide a basis for an effective approach to PDT for AMD.
It has been shown that vaccination with peptides derived from human vascular endothelial growth factor receptor 2 (VEGFR2) induces cytotoxic T lymphocytes (CTLs) with potent cytotoxicity against endothelial cells expressing VEGFR2 in a A2/Kb transgenic mice system expressing human HLA-A^*0201. We examined the efficacy of immunotherapy against AMD using a CNV model. The fluorescent leakage index in the peptide vaccination group was reduced to 80% and the CNV area to 18% compared with the control group This model provides a rationale for immunotherapy using the epitope peptides derived from VEGFR2 for the treatment of CNV.
In order to elucidate the molecular mechanisms of development of the fovea, which is composed mainly of cone photoreceptors and susceptible to injury from AMD, we performed a comparative gene expression analysis between the central and peripheral regions of the monkey retina using monkey (Rhesus Macaque) genome microarray chips. We then selected the clones which were expressed at significantly higher levels in the central region and confirmed their expression in the monkey retina by section in situ hybridization. This study sheds light on the mechanisms of fovea development and may lead to thedevelopment of regenerative medicine for cone photoreceptors.
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