Establishment of a Novel Therapeutic Strategy for Neurotrophic Keratopathy by Targeting the Tenesin X-TRP Channel System
Project/Area Number |
18K09419
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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 | Wakayama Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
雑賀 司珠也 和歌山県立医科大学, 医学部, 教授 (40254544)
岡田 由香 和歌山県立医科大学, 医学部, 教授 (50264891)
山中 修 和歌山県立医科大学, 医学部, 博士研究員 (50254545)
平井 秀一 和歌山県立医科大学, 医学部, 教授 (80228759)
松本 健一 島根大学, 学術研究院医学・看護学系, 教授 (30202328)
小出 隆規 早稲田大学, 理工学術院, 教授 (70322253)
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Project Period (FY) |
2018-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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Keywords | テネイシンX / 角膜創傷治癒 / マトリセルラー蛋白質 / 角膜上皮創傷治癒 / TRPチャネル / 神経麻痺生角膜症 |
Outline of Final Research Achievements |
The purpose of the study was to uncover the role of tenascin X in modulation of healing in mouse corneas subjected to epithelium debridement. Tenascin X protein was upregulated in the wounded wild-type (WT) corneal epithelium. Loss of tenascin X prolonged corneal epithelial wound healing and increased neutrophilic inflammatory response to debridement in mice. Although tenascin-deficient (KO) mice showed delayed regeneration of corneal sensory nerves, there was no difference in TRPV1, TRPV4, or TRPA1 expression between WT and KO mice. Tenascin X contributes to the control of neutrophil infiltration needed to support the regenerative response to injury and prevent the oxidative stress mediators from rising to cytotoxic levels.
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Academic Significance and Societal Importance of the Research Achievements |
テネイシンX欠失(KO)マウスでは好中球浸潤の制御が阻害されることで角膜上皮の治癒が遅延していた。またKOマウスでは角膜のコラーゲン線維の密度が低下しており、角膜上皮のみならず角膜実質の創傷治癒の遅延も確認された。これらの研究結果からテネイシンXを原因遺伝子としたエーラス・ダンロス症候群の患者では角膜外傷ひいては角膜切開での白内障手術時に創傷治癒が遅延する可能性が高いと考え感染対策あるいは創縫合など慎重に個別対応を検討する必要があると考えられた。
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Report
(6 results)
Research Products
(24 results)
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[Journal Article] Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4.2019
Author(s)
Okada Y, Sumioka T, Ichikawa K, Sano H, Nambu A, Kobayashi K, Uchida K, Suzuki Y, Tominaga M, Reinach PS, Hirai SI, Jester JV, Miyajima M, Shirai K, Iwanishi H, Kao WW, Liu CY, Saika S.
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Journal Title
Lab Invest.
Volume: 99(2)
Issue: 2
Pages: 210-230
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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