Study on the molecular mechamisms of leukocyte stasis in retinal microcirculation abnormality-possible roles of TNF-a
| Project/Area Number |
17591849
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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 | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
YOSHIDA Munenori Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院医学研究科, 助教授 (60273447)
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| Co-Investigator(Kenkyū-buntansha) |
OGURA Yuichiro Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院医学研究科, 教授 (70191963)
SAKURAI Eiji Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院医学研究科, 講師 (30305528)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | leukocyte / retinal microcirculation / TNF-a / 糖尿病網膜症 / ぶどう膜炎 |
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| Research Abstract |
Injection of TNF-alpha into vitreous body caused severe inflammatory change in the treated eye as a dose-dependent Manner. Acridine orange digital fluorography (APDF) was performed to evaluate the leukostasis in this TNF-induced ocular inflammation. The number of leukocytes Accumulated in the retina was significantly increased in the TNF-treated eye.
Leukocyte adhesion to retinal vascular endothelial cells were measured by the following method. Human retinal vascular endothelial cells (hRVEC) were cultured as a monolayer. Human leukocytes were co-cultured on the hRVEC. For hours, then rinsed. The number of adhered leukocytes were measured by myeloperoxidase (MPO) assay. The effect of TNF-a, high glucose, and high insulin were studied. TNF-a, as well as high glucose, high insulin had an effect to increase the leukocyte adhesion to hRVECs. However the concentration of TNF-a was not increased in the conditioned medium of high glucose and high insulin. Thus TNF-a was thought not to be the key factor for the increase of adhesion between leukocytes and hRVECs.
It is known that leukostasis is increased in the eyes of diabetic rat model. The expression of TNF-a was measured in the diabetic rat eyes. The mRNA expression and the bioactivity of TNF-a was measured. Both mRNA expression in the retina and the bioactivity of TNF-a in the vitreous fluid were not increased in the diabetic rat eyes The antibody for TNF-a did not decrease the accumulation of leukocytes in the diabetic rat retina. On the other hand, The neutralizing antibody for TNF-a significantly decreased the accumulating leukocytes in the retina in endotoxin induced uveitis (EIU). The inflammatory changes evaluated by the scoring and the protein concentration in the aqueous was also decreased in the anti-TNF-a antibody treated EIU eyes.
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Report
(3 results)
Research Products
(1 results)
