We investigate the neuroprotective mechanisms in glaucoma against oxidative stress, the Keap1/Nrf2 pthway.
| Project/Area Number |
18K09435
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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 | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中澤 徹 東北大学, 医学系研究科, 教授 (30361075)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 酸化ストレス / 緑内障 / 神経保護 / Nrf2 / ミトコンドリア障害 / ミューラー細胞 / ロテノン / グリア細胞 |
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| Outline of Final Research Achievements |
Mitochondria are known as one of the endogenous reactive oxygen species producing organs. Mitochondrial damage and oxidative stress are thought to be closely related. It was revealed that retinal Mueller cells are activated in Nrf2 knockout mice that are vulnerable to oxidative stress when mitochondrial damage is caused by the Complex I inhibitor rotenone. Rotenone was added, and we investigated the difference in neuroprotective factor / antioxidant enzyme secretion mechanism between Nrf2KO mice and wild-type mice. There is a significant increase in neuroprotective factors in the Mueller cells of Nrf2KO mice as compared with the wild type.
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| Academic Significance and Societal Importance of the Research Achievements |
ロテノン存在下、野生型ミュラー細胞では抗酸化酵素の発現が増加して神経保護に働き、Nrf2 KOミュラー細胞では、代償的に神経栄養因子の発現が増強され、神経保護効果をもたらすことが示唆された。ヒトを対象とした臨床研究のみでは限界があり、動物モデルを使った基礎研究の蓄積が重要である。既に緑内障病態への酸化ストレスやグリア細胞の寄与が明らかになっていることから、酸化ストレス暴露時のミューラー細胞の果たす役割が解明され、酸化ストレスに脆弱なヒトに対しグリア細胞を標的とした緑内障治療戦略が展開される可能性が大いに期待される。
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Report
(4 results)
Research Products
(13 results)
