2002 Fiscal Year Final Research Report Summary
The pathological investigation of proliferative diabetic retinopathy based on the control of retinal pericytes
| Project/Area Number |
12470363
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
TAKAGI Hitoshi Department of Ophthalmology and Visual Science, Kyoto University, Lecturer, 医学研究科, 講師 (70283596)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIWAKI Hirokazu Department of Ophthalmology and Visual Science, Kyoto University, Instructor, 医学研究科, 助手 (90303841)
KIRYU Junichi Department of Ophthalmology and Visual Science, Kyoto University, Lecturer, 医学研究科, 講師 (80281096)
KASHII Satoshi Department of Ophthalmology and Visual Science, Kyoto University, Associate Professor, 医学研究科, 助教授 (50194717)
SUZUMA Kiyoshi Department of Ophthalmology and Visual Science, Kyoto University, Instructor, 医学研究科, 助手 (80335265)
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| Project Period (FY) |
2000 – 2002
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| Keywords | endothelial cells / pericytes / angiopoietin 2 / AT 1 receptor / angiotensin / diabetic retinopathy / retinal edema / PDGF-receptor |
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| Research Abstract |
In this research, we investigated the control mechanism of retinal endothelial cells and pericytes, and aimed at a new therapeutic development of intraocular vascular proliferative diseases. In a diabetic retinopathy, pericyte loss is known to cause microaneuiysms and vascular hyperpermiability. In streptozotocine-induced diabetic rats, angiopoietine 2 is proved to be highly expressed after 6 months from onset of diabetes by RT-PCR analyses, and pericyte loss is observed by in situ hybridization and double immune staining analyses in the retinal cite where angiopoietine 2 is expressed. (IOVS 2003;44;393-402). In the eyes of diabetic retinopathy, angiotensin 2 selectively potentiates angiopoietine 2 in retinal endothelial cells, and this suggests the role of angiotensin 2 in the relation between endothelial cells and pericytes. (Diabetes 2001;50;867-875). These results are highly evaluated as a basic data on clinical trials, such as DIRECT study. In the next, we aimed a new therapeutic development on such vessels in which pericytes are degenerated. The injection of an antagonistic mAb against PDGFR-beta into murine neonates provides such pericyte loss of retinal vessels, and vessels of such mice are poorly remodeled and leaky. This model resembles a pathological change in diabetic retinopathy. We show that addition of recombinant modified angiopoietin 1 restored a hierarchical valculature, and also rescued retinal edema and hemorrhage in the complete absensce of pericytes. These observations demonstrate the potential of angiopoietin 1 as a new therapeutic modality for pericyte loss in diseases such as diabetic retinopathies. (JCI 2002;110;1619-28). Angiopoietin 1 and angiotensin type 1 receptor blocker are possible to be an effective drug in a diabetic retinopathy.
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