Elucidation of a role of an energy metabolism regulator in development of subretinal fibrosis
Project/Area Number |
18K09471
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56060:Ophthalmology-related
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Research Institution | Kyushu University (2020) National Hospital Organization, Kyushu Medical Center (Clinical Institute) (2018-2019) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
園田 康平 九州大学, 医学研究院, 教授 (10294943)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 加齢黄斑変性 / 眼炎症 / ぶどう膜炎 / サイトカイン / 眼免疫 / 眼内悪性リンパ腫 / 網膜下線維瘢痕化 / 網膜色素上皮細胞 / 脈絡膜血管新生 / マクロファージ / Tリンパ球 / 制御性サイトカイン / 悪性リンパ腫 / ニューロメジンU / ニューロメジンU受容体 / 神経ペプチド |
Outline of Final Research Achievements |
In murine experimental chorodail neovascularization model, development of subretinal fibrosis was decreased in the eyes of Neuromedin U (NmU)-/- mice compared to that of NmU+/+ mice. The volume of subretinal fibrosis was significantly inhibited by intravitreous administration of NmU in a dose dependent manner. Expression of α-smooth muscle actin (SMA), which is a marker for epithelial mesenchymal transition (EMT), was examined on NmU+/+, NmU receptor (R) 1-/-, or NmUR2-/- retinal pigment epithelium (RPE) cells during co-culture with activated peritoneal macrophages (PEM) with or without intravitreous administration of NmU by immunohistochemistry. Expression of α- SMA was inhibited by NmU administration on all of NmU+/+, NmUR 1-/-, and NmUR2-/- RPE cells during co-culture with activated PEMs. Thus, these results suggest that NmU play a suppressive role in the development of subretinal fibrosis through activation of unknown receptors other than NmUR1 and NmUR2.
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Academic Significance and Societal Importance of the Research Achievements |
加齢黄斑変性(AMD)は欧米において中途失明原因第1位の疾患であり、わが国でも急激な高齢化に伴い罹患者数も増加の一途を辿っている。AMDにおける視力低下の約9割が視機能に重要な黄斑部に脈絡膜血管新生(CNV)、続いて起こる網膜下線維瘢痕化により視力障害が不可逆となる。CNVに対して血管内皮増殖因子(VEGF)を標的とした薬剤が開発され、保険適応となり、有効である。しかし、抗VEGF療法後に網膜下線維瘢痕化が増悪する報告があり、網膜下線維瘢痕化の治療法の開発が急務となっているが、未だ実用化されていない。本研究結果からNmUの網膜下線維瘢痕化抑制機構の解明が新規治療法開発につながる可能性がある。
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Report
(4 results)
Research Products
(45 results)
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[Journal Article] Variants in IL23R-C1orf141 and ADO-ZNF365-EGR2 are associated with susceptibility to Vogt-Koyanagi-Harada disease in Japanese population.2020
Author(s)
Sakono T, Meguro A, Takeuchi M, Yamane T, Teshigawara T, Kitaichi N, Horie Y, Namba K, Ohno S, Nakao K, Sakamoto T, Sakai T, Nakano T, Keino H, Okada AA, Takeda A, Ito T, Mashimo H, Ohguro N, Oono S, Enaida H, Okinami S, Horita N, Ota M, Mizuki N.
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Journal Title
PLoS One
Volume: 15
Issue: 5
Pages: 233464-233464
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-term efficacy of infliximab treatment and the predictors of treatment outcomes in patients with refractory uveitis associated with Behcet’s disease.2018
Author(s)
(1)Ueda S, Akahoshi M, Takeda A, Inoue Y, Omoto A, Ayano M, Kimoto Y, Mitoma H, Arinobu Y, Niiro H, Tsukamoto H, Horiuchi T, Hikita SI, Fukuhara T, Ishibashi T, Sonoda KH, Akashi K
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Journal Title
Eur J Rheumatol
Volume: 5
Issue: 1
Pages: 9-15
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Vitreous levels of interleukin-35 as a prognostic factor in B-cell vitreoretinal lymphoma2020
Author(s)
Takeda A, Hasegawa E, Nakao S, Ishikawa K, Murakami Y, Hisatomi T, Arima M, Yawata N, Oda Y, Kimura K, Yoshikawa H, Sonoda KH
Organizer
The 59th Annual Meeting of Japanese Retina and Vitreous Society
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