2007 Fiscal Year Final Research Report Summary
The relation ofATM in the pathology of retinal and chuoidal neovascularization
| Project/Area Number |
18591933
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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 | Keio University |
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Principal Investigator |
INOUE Makoto Keio University, School of Medicine, assistant professor (20232556)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Susumu Keio University, School of Medicine, assistant professor (10245558)
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| Project Period (FY) |
2006 – 2007
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| Keywords | angiogenesis / oxidative stress / VEGF / Retina / Age-related macula degeneration |
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| Research Abstract |
The ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps control the rate at which cells grow and divide. The ATM protein also assists cells in recognizing damaged or broken strands of DNA. Moreover, the appearance of disease of a malignant tumor such as the lymphoid tumors is admitted in high frequency in the patients of ataxia telangiectasia, and gene mutation and loss of Atm are found in the tumor cells. The function of DNA restoration is injured in the tumor cell that has the Atm gene mutation, and it is suggested that the function loss of the ATM relate to carcinogenesis.
Recently, it is shown that the self-renewal capacity of hematopoietic stem cells depends on ATM-mediated inhibition of oxidative stress in ATM KO mice. (Ito K, et al. Nature 2004, 997-1002). Then, we hypothesize that the background for the diabetic retinopathy such as the oxidative stresses can be improved by properly controlling the ATM.
By perfusion-labeling method with fluorescein-isothiocyanate (FITC)-coupled concanavalin A lectin (Con A), we show that the number of adherent leukocytes was significantly higher in Atm+/- mice and Atm-/- mice than in C57BL/6 normal mice. Moreover, the number of adherent leukocytes doesn't change with making the STZ diabetic model. The oxidative stress is known to be accelerated in the STZ diabetic model mice, and so these results imply that the accelerated stress is influenced by ATM.
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