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To elucidate the mechanism of retinal reperfusion by activated protein C

Research Project

Project/Area Number 15K10893
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionAichi Medical University

Principal Investigator

Kamei Motohiro  愛知医科大学, 医学部, 教授 (40281125)

Co-Investigator(Kenkyū-buntansha) 植村 明嘉  名古屋市立大学, 大学院医学研究科, 教授 (30373278)
西田 健太郎  大阪大学, 医学系研究科, 助教 (70624229)
福嶋 葉子  大阪大学, 医学系研究科, 助教 (70647031)
坂口 裕和  大阪大学, 医学系研究科, 寄附講座准教授 (80379172)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords網膜 / 網膜虚血性疾患 / 網膜再灌流 / 神経保護 / 活性型プロテインC(APC) / 網膜アストロサイト / 血管内皮細胞 / 血行再建 / APC(活性化プロテインC) / 網膜血管周皮細胞 / 虚血性疾患 / APC(活性型プロテインC) / 活性化プロテインC / 網膜血管内皮細胞 / 網膜神経節細胞 / 網膜神経保護
Outline of Final Research Achievements

To examine the retinal reperfusion by activated protein C (APC), APC was administered into the eyes of P12 oxygen-induced retinopathy (OIR) mice, and the area of the non-administration group and the retinal ischemic area was measured at P17. The retinal ischemic area of the APC administration group was narrower than that of the control group, and the retinal ischemia improving effect by APC could be confirmed in the OIR mice. In addition, we examined which cells that constitute the retinal blood vessels had an effect on APC, and the cell density of retinal astrocytes decreased in the area of the retinal ischemia from P12 after hyperoxia, but was reduced in the APC administration group. Remaining retinal astrocytes in the blood region suggested that APC might protect the retinal astrocytes.

Academic Significance and Societal Importance of the Research Achievements

活性型プロテインC(APC)の網膜血管再生効果をみるため、酸素誘発網膜症(OIR)モデルマウスの眼内にAPCを投与し、網膜虚血領域の面積を測定した結果、APCによる網膜虚血改善効果が確認できた。また、APCが網膜血管を構成するどの細胞に効果を及ぼしているか検討し、高酸素投与後から網膜虚血領域において網膜アストロサイトの細胞密度が減少するが、APC投与群において虚血領域の網膜アストロサイトが残存していることから、APCの網膜アストロサイト保護作用が示唆された。これらの結果と今後さらにAPCの作用機序が解明されれば、新たな虚血性網膜疾患治療薬としてのAPCの可能性が高まると考えられる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016 2015

All Journal Article (19 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] Efficacy and safety of intravitreal drug injections using a short 34-gauge needle2019

    • Author(s)
      Sasajima Hirofumi、Tsuboi Kotaro、Murotani Kenta、Kamei Motohiro
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 63 Issue: 3 Pages: 269-275

    • DOI

      10.1007/s10384-019-00663-w

    • NAID

      40021885413

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrophysiological evaluation of a chronically implanted electrode for suprachoroidal transretinal stimulation in rabbit eyes2019

    • Author(s)
      Nishida Kentaro、Sakaguchi Hirokazu、Kamei Motohiro、Saito Toru、Fujikado Takashi、Nishida Kohji
    • Journal Title

      Journal of Artificial Organs

      Volume: 印刷中 Issue: 3 Pages: 237-245

    • DOI

      10.1007/s10047-019-01095-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated Protein C for Ischemic Central Retinal Vein Occlusion: One-Year Results2019

    • Author(s)
      Hara Chikako、Kamei Motohiro、Sakaguchi Hirokazu、Matsumura Nagakazu、Sakimoto Susumu、Suzuki Mihoko、Nishida Kentaro、Fukushima Yoko、Nishida Kohji
    • Journal Title

      Ophthalmology Retina

      Volume: 3 Issue: 1 Pages: 93-94

    • DOI

      10.1016/j.oret.2018.07.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization2019

    • Author(s)
      Hayashi H, Mamun AA, Takeyama M, Yamamura A, Zako M, Yagasaki R, Nakahara T, Kamei M, Sato M
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1560-1560

    • DOI

      10.1038/s41598-018-38067-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The impact of spot size, spacing, pattern, duration and intensity of burns on the photocoagulation index in a geometric simulation of pan‐retinal laser photocoagulation2018

    • Author(s)
      Nishida Kentaro、Miura Ken、Sakaguchi Hirokazu、Kamei Motohiro、Wakabayashi Taku、Hara Chikako、Sakimoto Susumu、Fukushima Yoko、Sayanagi Kaori、Sato Shigeru、Fukuda Masakatsu、Nishida Kohji
    • Journal Title

      Acta Ophthalmologica

      Volume: 97 Issue: 4

    • DOI

      10.1111/aos.13939

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chorioretinal Shunt Vessel in Eyes with Central Retinal Vein Occlusion after Radial Optic Neurotomy2018

    • Author(s)
      Tsuboi Kotaro、Sasajima Hirofumi、Kamei Motohiro
    • Journal Title

      Ophthalmology

      Volume: 125 Issue: 9 Pages: 1409-1409

    • DOI

      10.1016/j.ophtha.2018.06.035

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential Observations of Conversion from Nonischemic to Ischemic Central Retinal Vein Occlusion Using Optical Coherence Tomography Angiography2018

    • Author(s)
      Fukutomi Akira、Tsuboi Kotaro、Ono Hikari、Ishida Yuichiro、Kamei Motohiro
    • Journal Title

      Case Reports in Ophthalmological Medicine

      Volume: 2018 Pages: 1-4

    • DOI

      10.1155/2018/1354217

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vitrectomy without prone positioning for rhegmatogenous retinal detachments in eyes with inferior retinal breaks2018

    • Author(s)
      Shiraki Nobuhiko、Sakimoto Susumu、Sakaguchi Hirokazu、Nishida Kentaro、Nishida Kohji、Kamei Motohiro
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 1 Pages: 1-9

    • DOI

      10.1371/journal.pone.0191531

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Randomized Trial of a Short 34-Gauge Needle for Intravitreal Injections2018

    • Author(s)
      Sasajima Hirofumi、Tsuboi Kotaro、Ono Hikari、Murotani Kenta、Kamei Motohiro
    • Journal Title

      Ophthalmology

      Volume: 125 Issue: 6 Pages: 1-2

    • DOI

      10.1016/j.ophtha.2018.01.038

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] SILICONE MICROTUBE?ASSISTED SCLERAL FIXATION OF A POSTERIOR CHAMBER INTRAOCULAR LENS2018

    • Author(s)
      Kataoka Takuya、Kamei Motohiro
    • Journal Title

      Retina

      Volume: 0 Issue: 1 Pages: 1-1

    • DOI

      10.1097/iae.0000000000002143

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unusual Case of Vogt-Koyanagi-Harada Disease Associated with SAPHO Syndrome: A Case Report2018

    • Author(s)
      Hasegawa Miyuki、Fukutomi Akira、Jinno Akiko、Fujita Kyoko、Kamei Motohiro
    • Journal Title

      Case Reports in Ophthalmology

      Volume: 9 Issue: 1 Pages: 202-208

    • DOI

      10.1159/000487226

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of oral tranexamic acid on macular edema associated with retinal vein occlusion or diabetes2017

    • Author(s)
      Takeyama Masayuki、Takeuchi Fumio、Gosho Masahiko、Sugita Keijiro、Zako Masahiro、Iwaki Masayoshi、Kamei Motohiro
    • Journal Title

      Clinical Ophthalmology

      Volume: Volume 12 Pages: 35-41

    • DOI

      10.2147/opth.s149935

    • NAID

      120007134595

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gap in Capillary Perfusion on Optical Coherence Tomography Angiography2017

    • Author(s)
      Tsuboi K, Ishida Y, Kamei M.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 58 Issue: 4 Pages: 2038-2043

    • DOI

      10.1167/iovs.17-21447

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simulation of panretinal laser photocoagulation using geometric methods for calculating the photocoagulation index.2017

    • Author(s)
      Nishida K, Sakaguchi H, Kamei M, Shiraki N, Oura Y, Wakabayashi T, Hara C, Fukushima Y, Sato T, Sayanagi K, Sato S, Fukuda M, Nishida K.
    • Journal Title

      Eur J Ophthalmol

      Volume: 27 Issue: 2 Pages: 205-209

    • DOI

      10.5301/ejo.5000865

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Short-term efficacy and safety of ranibizumab for macular oedema secondary to retinal vein occlusion in Japanese patients.2017

    • Author(s)
      Kamei M, Terasaki H, Yoshimura N, Shiraga F, Ogura Y, Grotzfeld AS, Pilz S, Ishibashi T.
    • Journal Title

      Acta Ophthalmol.

      Volume: 印刷中 Issue: 1

    • DOI

      10.1111/aos.13196

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] One-year outcome of 49-channel suprachoroidal–transretinal stimulation prosthesis in patients with advanced retinitis pigmentosa2016

    • Author(s)
      Fujikado T, Kamei M, Sakaguchi H, Kanda H, Endo T, Hirota M, Morimoto T, Nishida K, Kishima H, Terasawa Y, Oosawa K, Ozawa M, Nishida K.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 57 Issue: 14 Pages: 6147

    • DOI

      10.1167/iovs.16-20367

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Problems Related to Anti-Vascular Endothelial Growth Factor Treatment for Retinal Vein Occlusion.2016

    • Author(s)
      Kamei M
    • Journal Title

      Nippon Ganka Gakkai Zasshi

      Volume: 120 Pages: 361-363

    • Related Report
      2016 Research-status Report
  • [Journal Article] Reperfusion of areas of ischemia in central retinal vein occlusion - reply.2015

    • Author(s)
      Kamei M, Nishida K.
    • Journal Title

      JAMA Ophthalmol.

      Volume: 133 Issue: 2 Pages: 228-9

    • DOI

      10.1001/jamaophthalmol.2014.4249

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of retinal nonperfusion using depth-integrated optical coherence tomography images in eyes with branch retinal vein occlusion.2015

    • Author(s)
      Sakimoto S, Gomi F, Sakaguchi H, Akiba M, Kamei M, Nishida K
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 56 Pages: 640-646

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] anti-PDGFRβ抗体を使用した遷延する網膜虚血モデルマウスの作成2018

    • Author(s)
      白木幸彦、植村明嘉、瓶井資弘
    • Organizer
      愛知眼科フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 活性化プロテインCは虚血網膜における血行再建を促進する2018

    • Author(s)
      山本敬子、植村明嘉、瓶井資弘
    • Organizer
      愛知眼科フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] APCは虚血領域のアストロサイトのTlxを上昇させ、正常な血管リモデリングを誘導する2017

    • Author(s)
      山本敬子、植村明嘉、瓶井資弘
    • Organizer
      愛知眼科フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] 虚血型網膜中心静脈閉塞症に対する活性化プロテインC(APC)の長期成績2016

    • Author(s)
      原千佳子
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-08
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 虚血型網膜中心静脈閉塞症に対する活性化プロテインC(APC)の長期成績2016

    • Author(s)
      Hara C, Kamei M
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Long term outcomes of intravitreal activated Protein C for ischemic central retinal vein occlusion2016

    • Author(s)
      Kamei M
    • Organizer
      XXXth Meeting of the Club Jules Gonin
    • Place of Presentation
      Bordeaux, France
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Current and Future Treatments for Retinal Vein Occlusion2016

    • Author(s)
      Kamei M
    • Organizer
      The 5th Annual Stanley Chang, MD Lectureship
    • Place of Presentation
      Columbia University, NY
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 慢性期BRVOの毛細血管障害とレーザー光凝固2015

    • Author(s)
      瓶井資弘
    • Organizer
      第32回日本眼循環学会
    • Place of Presentation
      東京
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2020-03-30  

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