Mechanisms of disease progression triggered by persistent Akt activation in retinopathy of prematurity
| Project/Area Number |
17K17859
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Ophthalmology
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 未熟児網膜症 / 血管新生 / 内皮細胞 / Aktシグナル / ノンコーディングRNA / 網膜血管新生 / 眼科学 / 網膜 |
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| Outline of Final Research Achievements |
In retinopathy of prematurity(ROP), abnormal retinal angiogenesis results from excessively produced VEGF. For mimicking the pathological condition in ROP, endothelial cells (ECs) were stimulated continuously with high concentrated VEGF. Long exposure of VEGF unexpectedly induced persistent phosphorylation of Akt in ECs. Also, the persistent phosphorylation of Akt disrupted cellular motility and augmented permeability even without VEGF stimulation. Forced activation of Akt in retinal ECs in mice caused human ROP-like vessel dilation and tortuosity. We have identified novel non-coding RNAs of which expression increase in ECs after long VEGF exposure. The ncRNA can associate Akt and consequently sustain Akt phosphorylation. The findings suggested the novel ncRNA is one of the exacerbation factors in ROP.
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| Academic Significance and Societal Importance of the Research Achievements |
未熟児網膜症でみられる異常新生血管は軽症例では自然消退する一方、重症例では異常血管はさらに増悪して網膜剥離を経て失明に至る。本研究では、重症化因子として内皮細胞のAktシグナルに着目した。病的環境において内皮細胞に誘導されるAkt持続活性という特異な現象を見出し、その活性調節機構を解明した。本研究の成果は、小児の主要な失明疾患である未熟児網膜症の病態解明と治療法開発に繋がると期待される。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Inhibition of stromal cell-derived factor-1α/CXCR4 signaling restores the blood-retina barrier in pericyte-deficient mouse retinas.2018
Author(s)
Omori K, Nagata N, Kurata K, Fukushima Y, Sekihachi E, Fujii N, Namba-Hamano T, Takabatake Y, Fruttiger M, Nagasawa T, Uemura A, Murata T
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Journal Title
JCI Insight
Volume: 3
Issue: 23
Pages: 120706-120706
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries.2018
Author(s)
Matsuda J, Namba T, Takabatake Y, Kimura T, Takahashi A, Yamamoto T, Minami S, Sakai S, Fujimura R, Kaimori JY, Matsui I, Hamano T, Fukushima Y, Matsui K, Soga T, Isaka Y.
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Journal Title
Autophagy
Volume: 14
Issue: 1
Pages: 53-65
DOI
Related Report
Peer Reviewed / Open Access
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