The inhibition of subretinal fibrosis by specific retinoic receptor ligands
| Project/Area Number |
17K11451
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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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| Research Field |
Ophthalmology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KIMURA Kazuhiro 山口大学, 大学院医学系研究科, 教授 (60335255)
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| Co-Investigator(Kenkyū-buntansha) |
山田 直之 山口大学, 大学院医学系研究科, 講師 (70437630)
寺西 慎一郎 山口大学, 医学部附属病院, 助教 (90649360)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 滲出型加齢黄斑変性 / レチノイン酸 / 網膜下線維性瘢痕 |
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| Outline of Final Research Achievements |
The retinoid signal pathway is related to the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE). Both RAR-αagonist (Am580) and RAR-γ agonist (parovalotene) inhibited RPE mediated collagen gel contraction in a concentration or time-dependent manner. These compounds also suppressed the expression of EMT related markers proteins including alpha-smooth muscle actin (α-SMA), fibronectin (FN) and Metalloproteinases (MMPs) Further, the expression of focal adhesion protein paxillin was attenuated in RPE treated with these compounds. Finally, we examined the effects of these compounds on the development of CNV and subretinal fibrosis in a mouse model that mimics these pathological processes in patients with neovascular age related macular degeneration (nAMD). Am580 and parovalotene had no significant effect on the development of CNV, but suppressed the development of subretinal fibrosis in model mouse induced by laser photocoagulation.
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| Academic Significance and Societal Importance of the Research Achievements |
加齢黄斑変性(AMD)の長期的な視力障害に網膜下線維性瘢痕形成が寄与している。本研究にてRARｓアゴニストが網膜下線維性瘢痕形成、収縮を抑制することが明らかになった。本研究で同定されたシグナル伝達経路や化合物が未だ中途失明原因の上位である加齢黄斑変性の視力予後改善への新たな治療ターゲットとなる可能性が示唆された。本研究は、AMDに加え線維性増殖組織形成を伴う他の難治性網膜硝子体疾患の網膜障害を防ぎ、視機能の維持に大きく貢献する可能性もあり、その臨床的意義は非常に重要である。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Prominin-1 Modulates Rho/ROCK-Mediated Membrane Morphology and Calcium-Dependent Intracellular Chloride Flux.2019
Author(s)
Hori A, Nishide K, Yasukuni Y, Haga K, Kakuta W, Ishikawa Y, Hayes MJ, Ohnuma SI, Kiyonari H, Kimura K, Kondo T, Sasai N.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 15911-15911
DOI
Related Report
Peer Reviewed / Open Access
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