2020 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| 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) |
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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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| 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 |
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| 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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| Free Research Field |
眼炎症
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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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