| Project/Area Number |
11671733
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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 |
KIRYU Junichi Kyoto University, Dept. of Ophthalmology, Lecturer, 医学研究科, 講師 (80281096)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI Hitoshi Kyoto University, Dept. of Ophthalmology, Lecturer, 医学研究科, 講師 (70283596)
KASHII Satoshi Kyoto University, Dept. of Ophthalmology, Assoc. Professor, 医学研究科, 助教授 (50194717)
HONDA Yoshihito Kyoto University, Dept. of Ophthalmology, Professor, 医学研究科, 教授 (90026930)
MANDAI Michiko Kyoto University, Dept. of Ophthalmology, Instructor, 医学研究科, 助手 (80263086)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | leukocyte / retina / diabetes |
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| Research Abstract |
Recently, leukocytes are thought to play a central role in inflammatory conditions such as ischemia-reperfusion injury and endotoxin-induced uveitis. At inflammatory sites, the recruitment of circulating leukocytes out of the vessels is thought to occur through a multistep cascade of leukocyte-endothelial interactions, involving sequential rolling, firm adhesion, and transmigration into inflamed tissues. During this multistep cascade of leukocyte infiltration, each process is mediated with distinct adhesion molecules and regulated elaborately.
Diabetes is associated with greater neural damage after transient cerebral ischemia. Using rats with streptozotocin-induced diabetes of 4 weeks duration, we investigated leukocyte-endothelial cell interactions after ischemia-reperfusion injury. Leukocyte rolling and accumulation throughout the period of reperfusion was significantly suppressed in diabetic rats compared with non-diabetic rats. In addition, neither preischemic insulin treatment to d
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iabetic rats nor preischemic glucose infusion to non-diabetic rats had a significant influence on leukocyte-endothelial cells interactions during reperfusion. High blood glucose concentration before induction of ischemia did not exacerbate leukocyte involvement in the postischemic retinal injury. In conclusion, diabetic retina showed suppressed leukocyte-endothelial cells interactions after transient ischemia, perhaps due to an adaptive mechanism that developed during the period of induced diabetes.
EIU is characterized by blood ocular barrier disruption and leukocyte infiltration. The treatment with ATIII, leukocyte rolling was substantially inhibited along the retinal veins, suppressing subsequent leukocyte infiltration into the vitreous cavity. Similarly, leukocyte infiltration and protein leakage into the aqueous humor were significantly reduced with ATlll treatment. The levels of P-selectin mRNA expression in both iris-ciliary body and retina, which were upregulated after LPS injection, were substantially lower in the ATIII-treated rats. ATIII treatment significantly inhibited inflammatory reactions induced with LPS.Its suppressive effects on P-selectin expression could contribute to the attenuation of leukocyte infiltration, possibly by inhibiting leukocyte rolling. The current findings suggest the therapeutic potency of ATIII for the treatment of inveterate veitis. Less
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