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Understanding the pathogenesis of idiopathic (unclassified) uveitis through serum microRNA analysis

Research Project

Project/Area Number 21K09682
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionKyorin University

Principal Investigator

Keino Hiroshi  杏林大学, 医学部, 教授 (90328211)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2023: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsぶどう膜炎
Outline of Research at the Start

本研究課題では特発性ぶどう膜炎の臨床像を明らかにするために特発性ぶどう膜炎を眼所見から肉芽腫性と非肉芽腫性に分類、各々の血清中に特異的に発現、または共通して発現しているmicroRNAを同定、さらにその結果から予測される遺伝子ネットワークを明らかにすることで、ぶどう膜炎の発症機序や病態形成の分子レベルでの理解、新しい治療標的分子の同定、さらに特発性ぶどう膜炎の病態理解・分類に有用なバイオマーカーの確立を目指す。

Outline of Final Research Achievements

There are some patients showing ocular clinical sings for probable ocular sarcoidosis proposed by the International Workshop on Ocular Sarcoidosis (IWOS) (3 or more out of 7 ocular sings), in whom ancillary testing did not meet the IWOS criteria. Clinical features including visual outcomes were similar between patients with ocular sarcoidosis (OS) and patients with idiopathic uveitis with ocular manifestations of sarcoidosis (suspected OS). We compared the miRNA profile in serum from healthy subjects (HS), patients with ocular sarcoidosis, and patients with suspected ocular sarcoidosis. Clustering analysis showed that serum miRNA profiles of diagnosed ocular sarcoidosis and suspected ocular sarcoidosis were both clearly distinguishable from HS. However, comparative analysis of the miRNA profiles showed highly similar patterns between diagnosed OS and suspected OS. These findings suggest that both groups may share a similar underlying molecular pathology regarding serum miRNA.

Academic Significance and Societal Importance of the Research Achievements

これまで特発性ぶどう膜炎を対象とした報告は少なく、その臨床像は不明な点が多い。本課題では特発性ぶどう膜炎の中でも眼サルコイドーシスに近似した臨床像を呈する患者群(眼サルコイドーシス疑い群)が存在すること、近年疾患バイオマーカーとして注目されているmicroRNAに注目し血清中の発現プロファイルを眼サルコイドーシス群と眼サルコイドーシス疑い群で機械学習の手法を用いてプロファイルを比較したところ両群間で近似した発現パターンを示すことを報告した。本課題で得られた結果を基に特発性ぶどう膜炎の疾患分類と病態理解が進展することで、視機能予後の改善に繋がることが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (39 results)

All 2024 2023 2022 2021 2020

All Journal Article (18 results) (of which Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (18 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Book (3 results)

  • [Journal Article] 小児ぶどう膜炎のマネージメント2024

    • Author(s)
      慶野博
    • Journal Title

      小児ぶどう膜炎のマネージメント

      Volume: 95 Pages: 320-326

    • Related Report
      2023 Annual Research Report
  • [Journal Article] 【眼科検査機器はこう使う!】広角眼底撮影 内科的病態2023

    • Author(s)
      慶野博
    • Journal Title

      【眼科検査機器はこう使う!】広角眼底撮影 内科的病態

      Volume: 132 Pages: 54-60

    • Related Report
      2023 Annual Research Report
  • [Journal Article] 【外来で見逃してはいけない疾患11~診断・治療のポイントを押さえる~】(5章)ぶどう膜炎を見逃すな!2023

    • Author(s)
      慶野博
    • Journal Title

      眼科グラフィック

      Volume: 12 Pages: 503-512

    • Related Report
      2023 Annual Research Report
  • [Journal Article] 眼科医の手引 COVID-19ワクチン接種後のぶどう膜炎(解説)2023

    • Author(s)
      慶野博
    • Journal Title

      日本の眼科

      Volume: 94 Pages: 600-601

    • Related Report
      2023 Annual Research Report
  • [Journal Article] COVID-19 vaccination-related intraocular inflammation in Japanese patients2023

    • Author(s)
      Nakayama M, Okada AA, Hayashi I, Keino H
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 261 Issue: 3 Pages: 897-899

    • DOI

      10.1007/s00417-022-05866-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A COVID-19 Risk Reduction Strategy for the Treatment of Acute Vogt-Koyanagi-Harada Disease Utilizing the Antiviral Potential of Cyclosporine.2022

    • Author(s)
      Nakayama M, Okada AA, Hayashi I, Ando Y, Watanabe T, Keino H
    • Journal Title

      Ocul Immunol Inflamm.

      Volume: - Issue: 2 Pages: 1-6

    • DOI

      10.1080/09273948.2022.2028293

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] A multicenter study of ocular inflammation after COVID-19 vaccination2022

    • Author(s)
      Yasaka Yuta、Hasegawa Eiichi、Keino Hiroshi、Usui Yoshihiko、Maruyama Kazuichi、Sonoda Koh-Hei、JOIS Uveitis Survey Working Group
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 67 Issue: 1 Pages: 14-21

    • DOI

      10.1007/s10384-022-00962-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Compromised blood flow of the optic nerve head in acute retinal necrosis2022

    • Author(s)
      Hayashi I, Keino H, Inoue M, Okada AA
    • Journal Title

      Clin Exp Ophthalmol.

      Volume: 6 Issue: 6 Pages: 685-687

    • DOI

      10.1111/ceo.14114

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of subfoveal choroidal thickness in new-onset acute Vogt-Koyanagi-Harada disease2022

    • Author(s)
      Nakayama M, Keino H, Watanabe T, Okada AA.
    • Journal Title

      Clin Exp Ophthalmol.

      Volume: 6 Issue: 6 Pages: 678-680

    • DOI

      10.1111/ceo.14088

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Automated Quantitative Analysis of Anterior Segment Inflammation Using Swept-Source Anterior Segment Optical Coherence Tomography: A Pilot Study2022

    • Author(s)
      Keino H, Aman T, Furuya R, Nakayama M, Okada AA, Sunayama W, Hatanaka Y
    • Journal Title

      Diagnostics

      Volume: 12 Issue: 11 Pages: 2703-2703

    • DOI

      10.3390/diagnostics12112703

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features and visual outcomes of ocular sarcoidosis at a tertiary referral center in Tokyo.2022

    • Author(s)
      Nagahori K, Keino H, Nakayama M, Watanabe T, Ando Y, Hayashi I, Abe S, Okada AA
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 260 Issue: 10 Pages: 3357-3363

    • DOI

      10.1007/s00417-022-05701-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] omparative Analysis of Serum microRNA in Diagnosed Ocular Sarcoidosis versus Idiopathic Uveitis with Ocular Manifestations of Sarcoidosis2022

    • Author(s)
      Saito S, Keino H, Takasaki I, Abe S, Kohno H, Ichihara K, Hayashi I, Nakayama M, Tsuboshita Y, Miyoshi S, Okamoto S, Okada AA
    • Journal Title

      Int J Mol Sci.

      Volume: 23 Issue: 18 Pages: 10749-10749

    • DOI

      10.3390/ijms231810749

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic Ablation of Nrf2 Exacerbates Neuroinflammation in Ocular Autoimmunity2022

    • Author(s)
      Sato Y, Saito S, Nakayama M, Sugita S, Kudo A, Keino H
    • Journal Title

      Int J Mol Sci.

      Volume: 23 Issue: 19 Pages: 11715-11715

    • DOI

      10.3390/ijms231911715

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Analysis of Retinal Vascular Leakage in Retinal Vasculitis Using Machine Learning2022

    • Author(s)
      Keino H, Wakitani T, Sunayama W, Hatanaka Y
    • Journal Title

      Appl. Sci.

      Volume: 12 Issue: 24 Pages: 12751-12751

    • DOI

      10.3390/app122412751

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating Vitreous microRNA as Possible Biomarker in High Myopic Eyes with Macular Hole.2022

    • Author(s)
      Ando Y, Keino H, Inoue M, Hirota K, Takahashi H, Sano K, Koto T, Sato T, Takeuchi M, Hirakata A.
    • Journal Title

      Int J Mol Sci

      Volume: 23 Issue: 7 Pages: 3647-3647

    • DOI

      10.3390/ijms23073647

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of in vivo expansion of regulatory T cells with IL-2/anti-IL-2 antibody complex plus rapamycin on experimental autoimmune uveoretinitis.2020

    • Author(s)
      SatoY, Keino H, Nakayama M, Kano M, Okada AA.
    • Journal Title

      Ocul Immunol Inflamm.

      Volume: - Issue: 7-8 Pages: 1520-1529

    • DOI

      10.1080/09273948.2020.1757119

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis2020

    • Author(s)
      Takase Hiroshi、Goto Hiroshi、Namba Kenichi、Mizuki Nobuhisa、Okada Annabelle A、Ohguro Nobuyuki、Sonoda Koh-Hei、Tomita Makoto、Keino Hiroshi、Kezuka Takeshi、Kubono Reo、Mizuuchi Kazuomi、Shibuya Etsuko、Takahashi Hiroyuki、Yanai Ryoji、Mochizuki Manabu
    • Journal Title

      Ocular Immunology and Inflammation

      Volume: - Issue: 1 Pages: 1-6

    • DOI

      10.1080/09273948.2020.1789179

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term efficacy of early infliximab-induced remission for refractory uveoretinitis associated with Behcet’s disease.2020

    • Author(s)
      Keino H, Watanabe T, Nakayama M, Komagata Y, Fukuoka K, Okada AA.
    • Journal Title

      Br J Ophthalmol

      Volume: - Issue: 11 Pages: 1525-1533

    • DOI

      10.1136/bjophthalmol-2020-316892

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 血清miRNAを用いた急性帯状潜在性網膜外層症および多発消失性白点症候群の比較2023

    • Author(s)
      齊藤翔子,慶野博,中山真紀子,林勇海,阿部慎也,中村友子,高崎一郎,安藤良将,長堀克哉,岡田アナベルあやめ
    • Organizer
      第127回日本眼科学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 感染性ぶどう膜炎の診断のプロセス2023

    • Author(s)
      慶野博
    • Organizer
      第127回日本眼科学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Clinical outcomes of adalimumab in real-world treatment of non-infectious uveitis from a single tertiary center in Tokyo2023

    • Author(s)
      Keino H, Nakayama M, Nagahori K, Saito S, Okada AA
    • Organizer
      FOCIS
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 難治性網膜血管炎に対してアダリムマブを導入した2例の臨床経過の検討2023

    • Author(s)
      長堀克哉,慶野博,中山真紀子,斎藤翔子,林勇海,安藤良将,渡辺交世,岡田アナベルあやめ
    • Organizer
      第56回日本眼炎症学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Clinical outcomes of adalimumab in real-world treatment of non-infectious uveitis from a single tertiary center in Tokyo2023

    • Author(s)
      慶野博,中山真紀子,長堀克哉,斎藤翔子,岡田アナベルあやめ
    • Organizer
      第51回日本臨床免疫学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Clinical outcomes of adalimumab in real-world treatment of non-infectious uveitis from a single tertiary center in Tokyo2023

    • Author(s)
      長堀克哉, 慶野博,中山真紀子,斎藤翔子,安藤良将,渡辺交世, 岡田アナベルあやめ
    • Organizer
      第77回日本臨床眼科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 前眼部OCT画像のテクスチャ特徴を用いたぶどう膜炎の前房細胞グレードの推定2023

    • Author(s)
      清水悠多,畑中裕司,慶野博
    • Organizer
      第4回日本眼科AI学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Multicenter posthoc analysis of Behcet disease uveoretinitis on infliximab treatment for 10 years2023

    • Author(s)
      Takeuchi T, Usui Y, Namba K, Keino H, Takeuchi M, Takase H, Kamoi K, Nagatani X, Itoh X, Nakai K, Maruyama K, Kobayashi E, Hori J, Mashita X, Satou T, Ohguro N, Okada AA, Sonoda K, Goto H, Mizuki N
    • Organizer
      第6回日本ベーチェット病学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] COVID-19パンデミックにおける急性期Vogt-小柳-原田病の治療選択2022

    • Author(s)
      中山真紀子, 慶野博, 林勇海, 安藤良将, 岡田アナベルあやめ
    • Organizer
      第126回日本眼科学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] MEWDSの日本人患者の特徴 全身ステロイドの投与が最終視力に及ぼす影響.2022

    • Author(s)
      近藤峰生, 齋藤航, 石田晋, 國吉一樹, 上野真治, 林孝彰, 中野匡, 早川卓浩, 角田和繁, 慶野博, 岡田アナベルあやめ, 中村考介, 秋山英雄
    • Organizer
      第126回日本眼科学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] ベーチェット病ぶどう膜炎に対するインフリキシマブ治療の5年以上の検討:多施設研究2022

    • Author(s)
      竹内大, 臼井嘉彦, 南場研一, 慶野博, 竹内正樹, 高瀬博, 鴨居功樹, 長谷敬太郎, 伊東崇子,中井慶, 丸山和一, 小林恵里, 堀純子, 真下永, 佐藤智人, 大黒伸行, 岡田アナベルあやめ, 園田康平, 後藤浩, 水木信久
    • Organizer
      第126回日本眼科学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] SUNワーキンググループによる25のぶどう膜炎疾患の分類基準.2022

    • Author(s)
      岡田アナベルあやめ, 望月學, 大野重昭, 慶野博, 高瀬博, 南場研一, 渡邊交世, 鴨居功樹
    • Organizer
      第126回日本眼科学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 眼炎症性疾患における炎症活動性の定量的評価法の確立と新たな治療戦略を目指して2022

    • Author(s)
      5.慶野博
    • Organizer
      第126回日本眼科学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 杏林アイセンターにおける特発性ぶどう膜炎患者の臨床像.2021

    • Author(s)
      林 勇海, 慶野博, 中山真紀子, 安藤良将, 渡邊交世, 岡田アナベルあやめ
    • Organizer
      第125回日本眼科学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Non-coding RNAの視点からみたぶどう膜炎の病態理解.2021

    • Author(s)
      慶野博
    • Organizer
      第54回日本眼炎症学会.
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 実験的自己免疫性ぶどう膜網膜炎(EAU)における血清中microRNA解析2021

    • Author(s)
      慶野博,齋藤翔子,佐藤康彦,髙﨑一朗,渡辺交世,岡田アナベルあやめ
    • Organizer
      第49回日本臨床免疫学会総会.
    • Related Report
      2021 Research-status Report
  • [Presentation] Management considerations in viral anterior uveitis.2021

    • Author(s)
      Keino H
    • Organizer
      International Ocular Inflammatory Society.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The changes of serum microRNA expression profile during the development of experimental autoimmune uveoretinitis.2021

    • Author(s)
      Keino H
    • Organizer
      International Ocular Inflammatory Society.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 眼科学レビュー 2023-2024 ぶどう膜 生物学的製剤によるぶどう膜炎治療2023

    • Author(s)
      慶野博
    • Total Pages
      7
    • Publisher
      総合医学社
    • Related Report
      2023 Annual Research Report
  • [Book] 眼科診療エクレール2 眼内悪性リンパ腫の診断 眼科画像診断パワーアップ2023

    • Author(s)
      慶野博
    • Total Pages
      6
    • Publisher
      中山書店
    • Related Report
      2023 Annual Research Report
  • [Book] 新 眼科診療クローズアップ  角膜後面沈着物と前房炎症のチェックポイント2023

    • Author(s)
      慶野博
    • Total Pages
      7
    • Publisher
      MEDICAL VIEW
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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