Development of strategic treatment based on the identification of novel susceptibility genes associated with age-related macular degeneration
| Project/Area Number |
16K15733
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Ophthalmology
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| Research Institution | Tottori University |
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Principal Investigator |
BABA Takashi 鳥取大学, 医学部附属病院, 講師 (40304216)
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| Co-Investigator(Kenkyū-buntansha) |
井上 幸次 鳥取大学, 医学部, 教授 (10213183)
宮崎 大 鳥取大学, 医学部, 准教授 (30346358)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 加齢黄斑変性 / 疾患モデルマウス / 血管新生 / 眼血管新生 / モデルマウス / ゲノム / 病理学 |
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| Outline of Final Research Achievements |
The purpose of this study was to determine the role of IL-4/IL-4Rα axis in age-related macular degeneration (AMD). Intraocular fluid screening of AMD patients identified significant higher levels of IL-4 than normal subjects. In AMD mouse model, CCR2+ bone marrow cells were recruited to early CNV lesions. IL-4+ bone marrow derived cells induced CCL2 which enhanced the recruitment of CCR2+ bone marrow derived cells. By analysis of bone marrow chimeric mice model using wild-type, Il4, Il4ra and Il13ra1-deficient mice and in vitro tube-formation assay, IL-4 expressing cells derived from bone marrow contribute AMD pathogenesis via IL-4α receptor instead of IL-13α1 receptor.
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| Academic Significance and Societal Importance of the Research Achievements |
加齢黄斑変性(AMD)は、有病率が高く、進行すると高齢者の視力を奪う。健康寿命の延長という観点からも、侵襲が少なく効果の高い治療法の開発が望まれる。しかし、AMDの病態については、まだ解明されていない点が多い。今回、我々の発見した骨髄由来細胞を介したIL-4による網膜下血管新生の発生機序は、明らかにされていなかったIL-4の血管新生への関与に着目したもので、局所組織における細胞間のコミュニケーションという新しい概念を導入したものである。この知見は新しい視点からのAMD治療の開発への礎となる可能性がある。また、AMDだけでなく、がんなどの血管新生が関連する疾患の治療法の開発への応用が期待できる。
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases2017
Author(s)
Miyazaki D, Fukushima A, Ohashi Y, Ebihara N, Uchio E, Okamoto S, Shoji J, Takamura E, Nakagawa Y, Namba K, Fujishima H.
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Journal Title
Ophthalmology
Volume: 124
Issue: 3
Pages: 287-294
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The effect of topical application of 0.15% ganciclovir gel on cytomegalovirus corneal endotheliitis.2016
Author(s)
Koizumi N, Miyazaki D, Inoue T, Ohtani F, Kandori-Inoue M, Inatomi T, Sotozono C, Nakagawa H, Horikiri T, Ueta M, Nakamura T, Inoue Y, Ohashi Y, Kinoshita S.
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Journal Title
Br J Ophthalmology
Volume: May 3
Issue: 2
Pages: 114-119
DOI
Related Report
Peer Reviewed / Open Access
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