| Project/Area Number |
20K09840
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | National Defense Medical College |
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Principal Investigator |
Takeuchi Masaru 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 教授 (40260939)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 正孝 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 再生発生学, 准教授 (30534896)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 糖尿病網膜症 / オステオポンチン / 網膜血管透過性 / ZO-1 / Claudin-5 / Claudine-5 / 糖尿病 / claudin-5 / 血液眼関門 / Th17細胞 / IL-17 / Th17 |
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| Outline of Research at the Start |
我々は、DMを自然発症するAkitaマウスとTh17細胞優位の分化誘導がみられるGKOマウスとを掛け合わせてAkita-GKOマウスを作成したところ、Akitaマウスよりも早期にDR所見を呈することが明らかになった．本研究では、１）より長期的にAkita-GKOマウスのDR所見を観察し、PDR様変化がみられるか、２）高血糖下でTh17細胞およびOPN産生T細胞へと分化したHMGB1反応性T細胞がDMの発症、DRの進行に関与しているのか、そして３）抗IL-17A抗体、抗HMGB1抗体、および抗OPN抗体の硝子体内投与によりAkita-GKOマウスのDRの進行を抑制できるか否かについて検討する．
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| Outline of Final Research Achievements |
Serum and retinal OPN concentrations in streptozotocin-induced diabetic mice (STZ mice) were significantly higher than those in control mice, and increased vascular hyperpermeability in the retina of STZ mice was reduced by intravitreal injection of anti-OPN neutralizing antibodies (anti-OPN Abs). The expression of claudin-5 and ZO-1, which consist of the retinal vascular barrier, was attenuated in the retina of STZ mice and ameliorated by anti-OPN Ab IVI. On the other hand, OPN Ab IVI inhibited neither gene expression nor protein level of vascular endothelial growth factor (VEGF) in the eye, indicating that retinal vascular permeability enhancement by OPN is VEGF-independent.
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| Academic Significance and Societal Importance of the Research Achievements |
Our results suggest that OPN induces tight junction disruption and vascular hyperpermeability under
diabetic conditions. Targeting OPN may be an effective approach to manage diabetic retinopathy.
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