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Establishment of new biomarkers for uveitis and development of treatments by transomics analysis

Research Project

Project/Area Number 19K09959
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Usui Yoshihiko  東京医科大学, 医学部, 准教授 (50408142)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords炎症性眼疾患 / ぶどう膜炎 / 人工知能 / 機械学習 / オミックス解析 / マイクロRNA / メタボローム / バイオマーカー
Outline of Research at the Start

ぶどう膜炎は視力障碍の主要な原因疾患の1つであるが、診断や治療効果判定に確立したバイオマーカーや治療法は未だない。本研究では、各種ヒトぶどう膜炎の臨床データおよび検体を用いて、病態をトランスオミックス解析で包括的に解明することで診断や治療効果判定におけるバイオマーカーを確立し、これらに対する新規治療法の開発も視野に入れる。その結果に基づいて候補因子をマウス実験的自己免疫性ぶどう膜炎に投与することにより、炎症が抑制できるかを個体および細胞レベルで検討することで新規病態メカニズムの解明と治療法を開発することを目的とする。

Outline of Final Research Achievements

Uveitis is one of the major causative diseases of visual impairment, but there are no established biomarkers or treatments for diagnosis and judgment of therapeutic effect. In this study, we make full use of bioinformatics and artificial intelligence to develop inflammatory eye diseases, from the results of general tests that have been performed in insurance clinics to the large amount of data obtained by the latest omics analysis. Created a new biomarker for. In particular, I was able to create new biomarkers for intraocular lymphoma, acute retinal necrosis, and endophthalmitis, which have poor visual acuity.

Academic Significance and Societal Importance of the Research Achievements

ベーチェット病やVogt-小柳-原田病などの非感染性ぶどう膜炎には疾患特異的なバイオマーカーが存在しないため、新規バイオマーカーの同定ができれば、早期診断に寄与できるのみならず、治療効果判定や再発の重要な指標となり得る。また、ぶどう膜炎との鑑別にしばしば苦慮する眼内リンパ腫では適切な診断が生命予後を左右するため、生命予後を推定することができるバイオマーカーを創出することができ、今後の個別化治療の基礎になるデータと思われる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (31 results)

All 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 14 results) Presentation (13 results) (of which Invited: 1 results)

  • [Int'l Joint Research] スクリプス研究所(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] ハーバード大学(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Programmed Cell Death-1 Pathway Deficiency Enhances Autoimmunity Leading to Dacryoadenitis of Mice.2021

    • Author(s)
      Sakurai Y, Usui Y, Hattori T, Takeuchi M, Takayama K, Karasawa Y, Nishio Y, Yamakawa N, Saitoh D, Goto H, Ito M.
    • Journal Title

      Am J Pathol

      Volume: in press Issue: 6 Pages: 1077-1093

    • DOI

      10.1016/j.ajpath.2021.02.014

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optical coherence tomography angiography for the diagnosis of granulomatosis with polyangiitis with serous retinal detachment: A case report2021

    • Author(s)
      Takashi N, Nakamura A, Kataoka K, Usui Y, Ito Y, Kaneko H.
    • Journal Title

      Medicine

      Volume: 100 Issue: 7 Pages: e24789-e24789

    • DOI

      10.1097/md.0000000000024789

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Share Differential Tissue Metabolic Signatures in IgG4-Related Ophthalmic Disease and Orbital Mucosa-Associated Lymphoid Tissue Lymphoma.2021

    • Author(s)
      Shimizu H, Usui Y, Wakita R, Aita Y, Tomita A, Tsubota K, Asakage M, Nezu N, Komatsu H, Umazume K, Sugimoto M, Goto H.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: in press Issue: 1 Pages: 15-15

    • DOI

      10.1167/iovs.62.1.15

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive Gene Analysis of IgG4-Related Ophthalmic Disease Using RNA Sequencing2021

    • Author(s)
      Asakage M, Usui Y, Nezu N, Shimizu H, Tsubota K, Umazume K, Yamakawa N, Umezu T, Suwanai H, Kuroda M, Goto H.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: in press Issue: 11 Pages: 3548-3548

    • DOI

      10.3390/jcm9113458

    • NAID

      120007183860

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-TNF-α Therapy for Refractory Uveitis Associated with Behçet's Syndrome and Sarcoidosis: A Single Center Study of 131 Patients2021

    • Author(s)
      Kunimi K, Usui Y, Asakage M, Maehara C, Tsubota K, Mitsuhashi R, Umazume A, Kezuka T, Sakai JI, Goto H.
    • Journal Title

      Ocul Immunol Inflamm

      Volume: in press Issue: 1 Pages: 223-230

    • DOI

      10.1080/09273948.2020.1791346

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitreous metabolomics profiling of proliferative diabetic retinopathy2021

    • Author(s)
      Tomita Y, Cagnone G, Fu Z, Cakir B, Kotoda Y, Asakage M, Wakabayashi Y, Hellström A, Joyal JS, Talukdar S, Smith LEH, Usui Y.
    • Journal Title

      Diabetologia

      Volume: 64 Issue: 1 Pages: 70-82

    • DOI

      10.1007/s00125-020-05309-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of Markers Predicting Clinical Course in Patients with IgG4-Related Ophthalmic Disease by Unbiased Clustering Analysis2020

    • Author(s)
      Tsubota K, Usui Y, Nemoto R, Goto H.
    • Journal Title

      J Clin Med

      Volume: 9 Issue: 12 Pages: 4084-4084

    • DOI

      10.3390/jcm9124084

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis.2020

    • Author(s)
      Shimizu H, Usui Y, Asakage M, Nezu N, Wakita R, Tsubota K, Sugimoto M, Goto H.
    • Journal Title

      J Clin Med

      Volume: 9 Issue: 12 Pages: 3955-3955

    • DOI

      10.3390/jcm9123955

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blockade of costimulatory CD27/CD70 pathway promotes corneal allograft survival2020

    • Author(s)
      Narimatsu A, Hattori T, Hiroki Ueno et al
    • Journal Title

      Experimental eye research

      Volume: 199 Pages: 108190-108190

    • DOI

      10.1016/j.exer.2020.108190

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Retinal microglia are critical for subretinal neovascular formation.2020

    • Author(s)
      Usui-Ouchi A, Usui Y, Kurihara T, Aguilar E, Dorrell MI, Ideguchi Y, Sakimoto S, Bravo S, Friedlander M.
    • Journal Title

      JCI insight

      Volume: 5 Issue: 12 Pages: 1391-1391

    • DOI

      10.1172/jci.insight.137317

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elucidation of Pathophysiology and Novel Treatment for Diabetic Macular Edema Derived from the Concept of Neurovascular Unit2020

    • Author(s)
      Usui Y
    • Journal Title

      JMA J

      Volume: 3 Issue: 3 Pages: 201-207

    • DOI

      10.31662/jmaj.2020-0022

    • NAID

      130007905844

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-Throughput MicroRNA Profiling of Vitreoretinal Lymphoma: Vitreous and Serum MicroRNA Profiles Distinct from Uveitis.2020

    • Author(s)
      Minezaki T, Usui Y, Asakage M, Takanashi M, Shimizu H, Nezu N, Narimatsu A, Tsubota K, Umazume K, Yamakawa N, Kuroda M, Goto H.
    • Journal Title

      J Clin Med.

      Volume: 9(6) Issue: 6 Pages: 1844-1844

    • DOI

      10.3390/jcm9061844

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in Etiology of Uveitis in a Single Center in Japan.2020

    • Author(s)
      Kunimi K, Usui Y, Tsubota K, Mitsuhashi R, Umazume A, Kezuka T, Sakai J, Goto H.
    • Journal Title

      Ocul Immunol Inflamm

      Volume: - Issue: 5 Pages: 976-981

    • DOI

      10.1080/09273948.2019.1709649

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Share Successful Treatment of Necrotizing Retinitis with Epstein-Barr Virus-Positive Ocular Fluid by Intravitreal Methotrexate Injection.2020

    • Author(s)
      Mashima A, Usui Y, Umazume K, Muramatsu D, Goto H.
    • Journal Title

      Ocul Immunol Inflamm

      Volume: 28 Issue: 4 Pages: 552-555

    • DOI

      10.1080/09273948.2019.1609047

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary Intraocular Methotrexate-related Lymphoproliferative Disorder in a Patient with Rheumatoid Arthritis Undergoing Long-term Methotrexate Therapy.2020

    • Author(s)
      Sone K, Usui Y, Fujii K, Goto H.
    • Journal Title

      Ocul Immunol Inflamm

      Volume: - Issue: 3 Pages: 456-459

    • DOI

      10.1080/09273948.2019.1668428

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of retinal pigment epithelium layer change in Vogt-Koyanagi- Harada disease with multicontrast optical coherence tomography2019

    • Author(s)
      Miura M, Makita S, Azuma S,Yasuno Y, Sugiyama S, Mino M, Yamaguchi T, Agawa T, Iwasaki T, Usui Y, Rao NA, Goto H
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 60 Issue: 10 Pages: 3352-3362

    • DOI

      10.1167/iovs.19-27378

    • NAID

      120007132697

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 炎症性眼疾患における新規バイオマーカーの創出-古典的検査からオミックス解析まで-2020

    • Author(s)
      臼井嘉彦
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 非感染性ぶどう膜炎の患者血清を用いた網羅的miRNAの解析2020

    • Author(s)
      朝蔭正樹、臼井嘉彦、禰津直也、清水広之、坪田欣也、山川直之、梅津知宏、高梨正勝、黒田雅彦、後藤浩
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] メタボロミクスによる血清を用いた3大ぶどう膜炎の鑑別2020

    • Author(s)
      清水広之、臼井嘉彦、禰津直也、朝蔭正樹、杉本昌弘、後藤浩
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] メタボロミクスを用いた眼サルコイドーシスにおける水溶性代謝物の網羅的解析2020

    • Author(s)
      菅原莉沙、清水広之、臼井嘉彦、坪田欣也、禰津直也、朝蔭正樹、杉本昌弘、後藤浩
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 眼内リンパ腫における硝子体液を用いたプロテオミクス解析2020

    • Author(s)
      坪田欣也、臼井嘉彦、禰津直也、朝蔭正樹、清水広之、山川直之、植田幸嗣、山口剛司、後藤浩
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 眼窩リンパ増殖性疾患におけるmiRNAの網羅的解析2020

    • Author(s)
      禰津直也、臼井嘉彦、朝蔭正樹、清水広之、坪田欣也、山川直之、高梨正勝、黒田雅彦、後藤浩
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 眼内リンパ腫とサルコイドーシス患者の硝子体および血清中の網羅的miRNA解析2020

    • Author(s)
      嶺崎輝海、臼井嘉彦、朝蔭正樹、禰津直也、清水広之、山川直之、成松明知、坪田欣也、馬詰和比古、黒田雅彦、後藤浩
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] サルコイドーシスによるぶどう膜炎に対するアダリムマブ導入例の検討2020

    • Author(s)
      國見敬子、臼井嘉彦、坪田欣也、馬詰朗比古、毛塚剛司、坂井潤一、後藤浩
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 眼内リンパ腫における採血結果および硝子体液中サイトカイン濃度を用いたクラスター解析2019

    • Author(s)
      坪田欣也、臼井嘉彦、後藤浩
    • Organizer
      第37回日本眼腫瘍学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 機械学習を用いた硝子体液中の免疫液性因子解析による眼内リンパ腫の識別検討2019

    • Author(s)
      禰津直也、臼井嘉彦、坪田欣也、朝蔭正樹、山川直之、黒田雅彦、斎藤彰、杉本昌弘、後藤浩
    • Organizer
      第37回日本眼腫瘍学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 眼内リンパ腫患者硝子体液および血清中における網羅的miRNA解析2019

    • Author(s)
      臼井嘉彦、朝蔭正樹、禰津直也、清水広之、成松明知、坪田欣也、馬詰和比古、後藤浩、黒田雅彦
    • Organizer
      第37回日本眼腫瘍学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 機械学習を用いた前房水中の免疫液性因子解析による眼内炎症性疾患の識別検討2019

    • Author(s)
      禰津直也、臼井嘉彦、朝蔭正樹、清水広之、斎藤彰、黒田雅彦、後藤浩
    • Organizer
      第73回日本臨床眼科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 眼サルコイドーシスにおける採血データを用いた階層型クラスター解析2019

    • Author(s)
      松島亮介、臼井嘉彦、清水広之、坪田欣也、後藤浩
    • Organizer
      第73回日本臨床眼科学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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