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The development of novel VEGF non-dependent therapy for the refractory retinal diseases

Research Project

Project/Area Number 17K16963
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionNagoya University

Principal Investigator

Kaneko Hiroki  名古屋大学, 医学部附属病院, 病院講師 (20647458)

Research Collaborator SHIMIZU hideyuki  
SUZUMURA ayana  
NAMBA rina  
YAMADA kazuhisa  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsVEGF / 糖尿病網膜症 / 加齢黄斑変性 / 増殖硝子体網膜症 / caveolin-1 / エイコサペンタエン酸 / ミュラー細胞 / 網膜電図 / Alu / Caveolin-1 / 網膜色素上皮細胞 / 上皮間葉転換 / 網膜 / microRNA / EPA
Outline of Final Research Achievements

Caveolin-1 was enhanced in the proliferation membrane of patients with proliferative vitreoretinopathy, and we confirmed similar changes in the mouse eye. Caveolin-1 was expressed in proliferating tissue has an effect of suppressing epithelial-mesenchymal transition of retinal pigment epithelial cells. Attenuation of the oscillatory potential (OP) wave of the electroretinogram (ERG) was confirmed in diabetic model rats and it was improved by oral administration of eicosapentaenoic acid (EPA). In addition, brain-derived trophic factor (BDNF) in Muller cells was elevated by EPA intake. In studies of age-related macular degeneration, Alu was administered into human RPE cells and in the eye of mice to confirm elevation of IL1β and IL18 and the reverse transcriptase inhibitor Lamivudine suppressed the increase of IL1β and IL18.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、現在加齢黄斑変性・糖尿病黄斑浮腫といった主要網膜疾患の多くが抗VEGF治療薬に強く依存しており、同時に抗VEGF治療薬が著効しない症例で治療の選択肢が著しく制限されることや抗VEGF薬の負の要素が注目されづらい状態を打開する策を模索するものである。VEGF受容体R2は網膜神経細胞に発現していることから、VEGFは網膜神経細胞の活性とも関連があり、糖尿病網膜症に対する抗VEGF薬使用には負の影響が懸念される。我々が確認したEPAによる網膜神経細胞保護効果は、糖尿病網膜症の長期的な神経保護という点で非常に重要であり、社会的失明患者を減少させる手段として検討の余地が十分あると考える。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Biological Characteristics of Subsilicone Oil Fluid and Differences With Other Ocular Humors.2019

    • Author(s)
      Shimizu H, Kaneko H, Suzumura A, Takayama K, Namba R, Funahashi Y, Kataoka K, Iwase T, Hwang SJ, Ito S, Yamada K, Ueno S, Ito Y, Terasaki H.
    • Journal Title

      Transl Vis Sci Technol

      Volume: 8 Issue: 1 Pages: 28-28

    • DOI

      10.1167/tvst.8.1.28

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Changes in refractive characteristics in Japanese children with Down syndrome2018

    • Author(s)
      Horio Junna、Kaneko Hiroki、Takayama Kei、Tuzuki Kinichi、Kakihara Hiroko、Iwami Miou、Kawase Yoshikatsu、Tsunekawa Taichi、Yamaguchi Naoko、Nonobe Norie、Terasaki Hiroko
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 62 Issue: 2 Pages: 231-236

    • DOI

      10.1007/s10384-018-0565-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Silicone oil-associated retinal light exposure under a surgical microscope2018

    • Author(s)
      Yamada K, Kaneko H, Tsunekawa T, Shimizu H, Suzumura A, Namba R, Takeuchi J, Kataoka K, Takayama K, Inoue M, Ito Y, Terasaki H.
    • Journal Title

      Acta Ophthalmol.

      Volume: - Issue: 5

    • DOI

      10.1111/aos.14038

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased Retinal Thinning after Combination of Internal Limiting Membrane Peeling and Silicone Oil Endotamponade in Proliferative Diabetic Retinopathy2017

    • Author(s)
      Kaneko Hiroki、Matsuura Toshiyuki、Takayama Kei、Ito Yasuki、Iwase Takeshi、Ueno Shinji、Nonobe Norie、Yasuda Shunsuke、Kataoka Keiko、Terasaki Hiroko
    • Journal Title

      Ophthalmologica

      Volume: 238 Issue: 4 Pages: 226-235

    • DOI

      10.1159/000479482

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Caveolin-1 for Blocking the Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy.2017

    • Author(s)
      Nagasaka Y, Kaneko H, Ye F, Kachi S, Asami T, Kato S, Takayama K, Hwang SJ, Kataoka K, Shimizu H, Iwase T, Funahashi Y, Higuchi A, Senga T, Terasaki H.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 58 Issue: 1 Pages: 221-229

    • DOI

      10.1167/iovs.16-20513

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological Involvement of MicroRNAs in Proliferative Vitreoretinopathy.2017

    • Author(s)
      Kaneko H, Terasaki H
    • Journal Title

      Transl Vis Sci Technol.

      Volume: 6 Issue: 4 Pages: 5-5

    • DOI

      10.1167/tvst.6.4.5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytokine profiling in the sub-silicone oil fluid after vitrectomy surgeries for refractory retinal diseases2017

    • Author(s)
      Kaneko Hiroki、Takayama Kei、Asami Tetsu、Ito Yasuki、Tsunekawa Taichi、Iwase Takeshi、Funahashi Yasuhito、Ueno Shinji、Nonobe Norie、Yasuda Shunsuke、Suzumura Ayana、Shimizu Hideyuki、Kimoto Reona、Hwang Shiang-Jyi、Terasaki Hiroko
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 2640-2640

    • DOI

      10.1038/s41598-017-03124-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optical Coherence Tomography Angiography of the Foveal Avascular Zone in Children With a History of Treatment-Requiring Retinopathy of Prematurity2017

    • Author(s)
      Nonobe N, Kaneko H, Ito Y, Takayama K, Kataoka K, Tsunekawa T, Matsuura T, Suzumura A, Shimizu H, Terasaki H.
    • Journal Title

      Retina

      Volume: - Issue: 1 Pages: 0-0

    • DOI

      10.1097/iae.0000000000001937

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Correlation between miR-148 Expression in Vitreous and Severity of Rhegmatogenous Retinal Detachment.2017

    • Author(s)
      Tsunekawa T, Kaneko H, Takayama K, Hwang SJ, Oishi A, Nagasaka Y, Ye F, Iwase T, Nonobe N, Ueno S, Ito Y, Yasuda S, Matsuura T, Shimizu H, Suzumura A, Kataoka K, Terasaki H.
    • Journal Title

      Biomed Res Int.

      Volume: 2017 Pages: 3427319-3427319

    • DOI

      10.1155/2017/3427319

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] “免疫・補体経路と網膜疾患”インストラクションコース, 網膜橋渡し研究アップデート2018

    • Author(s)
      兼子裕規
    • Organizer
      第72回日本臨床眼科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Possible causes of silicone-oil related vision loss in RD and PVR2018

    • Author(s)
      Hiroki Kaneko
    • Organizer
      The 12th Asia-Pacific Vitreo-retina Society (APVRS) Congress
    • Related Report
      2018 Annual Research Report
  • [Presentation] Optical Coherence Tomography Angiography of the Foveal Avascular Zone in Children With a History of Treatment-Requiring Retinopathy of Prematurity2018

    • Author(s)
      Kaneko H.
    • Organizer
      APAO2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cytokine profiling in the sub-silicone oil fluid after vitrectomy surgeries for refractory retinal diseases2017

    • Author(s)
      Kaneko H.
    • Organizer
      EURETINA2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2020-03-30  

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