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New strategy to treat diabetic retinopathy using stabilization of hyalocyte-vasucular endothelial cell correlation

Research Project

Project/Area Number 21592215
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionYamagata University

Principal Investigator

YAMASHITA Hidetoshi  山形大学, 医学部, 教授 (90158163)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Teiko  山形大学, 医学部, 准教授(現在:要町やまもと眼科医院長) (00297706)
GOTO Sakiko  山形大学, 医学部・眼科学, 助教 (40444038)
KASHIWAGI Yoshiko  山形大学, 医学部, 客員助教(現在:山形県立米沢女子短期大学助手) (90375345)
ABE Sachi  山形大学, 医学部, 医員 (90550658)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病黄斑浮腫 / 網膜内境界膜 / 硝子体細胞 / グリア細胞 / 網膜ー硝子体界面 / 血管内皮細胞 / ステロイド / 点眼約治療 / 炎症性サイトカイン / ヒアルロン酸 / ステロイド点眼 / 非観血的治療 / 点眼治療 / 眼内移行 / 網膜-硝子体界面 / 網膜-硝子体海面
Research Abstract

Ocular angiogenesis is regulated by polypeptides including cytokines, which are known to affect vascular endothelial cells. We have investigated that hyalocytes interact with vascular endothelial cells, and some cytokines affect these interactions. To determine the effect of various chemically active agents on the viability of endothelial cells alone and cocultured with hyalocytes. The viability of human retinal endothelial cells (HREC_s) was determined after exposure to IL-1α, IL-1β, IL-6, TNFα and VEGF using the MTT assay. These results were compared to the viability when the HRECs were cocultured with porcine hyalocytes that had been exposed to different types of cytokines. The effects of bevacizumab, fenofibrate and dexamethasone on the viability of HRECs in coculture with hyalocytes were also assessed. Ten micrograms/millilitre of bevacizumab decreased the percentage of living HRECs stimulated by VEGF without hyalocytes, but with the hyalocytes, 100 μg/ml of bevacizumab was requir … More ed to decrease the percentage of viable HRECs stimulated by VEGF. Dexamethasone at 50 μg/ml, decreased the viability of HRECs stimulated by IL-1α, IL-1β, IL-6 and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured. Coculturing HRECs with vitreous-derived hyalocytes depressed the effects of cytokines, bevacizumab, fenofibrate and dexamethasone. This suggests that the vitreal hyalocytes may play a role in pathogenic endothelial cell proliferation in vivo. In addition, inflammatory processes play important roles in diabetic retinopathy and maculopathy involving hyalocytes and endothelial cells.
Upon the above results, we examined the effects of steroid eye drops to treat diabetic maculopathy. We evaluated the efficacy of treatment refractory diabetic macular edema (DME) after vitrectomy with difluprednate ophthalmic emulsion 0.05% (DurezolR). This study enrolled patients with refractory diabetic macular edema in our clinic. In all subjects, more than 3 months had passed since any prior treatments. The subject eyes were treated with Durezol^(R) 4 times daily for the first month, and then twice daily for 2 months (eye drop group). The mean retinal thickness was improved significantly. Instillation of difluprednate ophthalmic emulsion 0.05% is a safe and effective treatment modality that does not require surgical intervention and does not produce severe side effects. Less

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (22 results)

All 2012 2011 2010 2009

All Journal Article (10 results) (of which Peer Reviewed: 6 results) Presentation (8 results) Book (1 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] 糖尿病網膜症の治療戦略2011

    • Author(s)
      山下英俊, 山本禎子, 川崎良, 佐藤浩章, 佐藤さくら, 斉藤公子, 後藤早紀子, 望月典子, 田邉祐資, 桐井枝里子, 阿部さち, 本間慶, 嘉山孝正
    • Journal Title

      臨床眼科

      Volume: 65 Pages: 1027-1041

    • NAID

      130007609292

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Treatment of diffuse diabetic macular oedema using steroid eye drops.2011

    • Author(s)
      Nakano Goto S, Yamamoto T, Kirii E, Abe, Yamashita H
    • Journal Title

      Acta Ophthalmologica

      Volume: (Epub ahead of print)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The in vitro response of human retinal endothelial cells to cytokines and other chemically-active agents is altered by co-culture with vitreous-derived hyalocytes2010

    • Author(s)
      Tojo N, Kashiwagi Y, Yamamoto S, Yamamoto T, Yamashita H
    • Journal Title

      Acta Ophthalmologica

      Volume: 88(3) Issue: 3

    • DOI

      10.1111/j.1755-3768.2010.01879.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Steroid eye drop treatment (difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema2010

    • Author(s)
      Nakano S, Yamamoto T, Kirii E, Abe S, Yamashita H
    • Journal Title

      Graefe's Archive for Clinical and Experimental Ophthalmology

      Volume: 248(6) Pages: 805-10

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 後天性網膜・硝子体疾患2010

    • Author(s)
      阿部さち, 山下英俊
    • Journal Title

      あたらしい眼科

      Volume: 27 Pages: 176-184

    • Related Report
      2011 Final Research Report
  • [Journal Article] The in vitro response of human retinal endothelial cells to cytokines and other chemically-active agents is altered by co-culture with vitreous-derived hyalocytes.2010

    • Author(s)
      Tojo N, Kashiwagi Y, Yamamoto S, Yamamoto T, Yamashita H
    • Journal Title

      Acta Ophthalmologica

      Volume: 88(3)(Epub 2010 Mar 23)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 後天性網膜・硝子体疾患2010

    • Author(s)
      阿部さち、山下英俊
    • Journal Title

      あたらしい眼科 27

      Pages: 176-184

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Steroid eye drop treatment(difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema2010

    • Author(s)
      Nakano S, Yamamoto T, Kirii E, Abe S, Yamashita H
    • Journal Title

      Graefe's Archive for Clinical and Experimental Ophthalmology

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cloning and characterization of cell strains derived from human corneal stroma and sclera.2010

    • Author(s)
      Kashiwagi Y, Nishitsuka K, Namba H, Kamiryo M, Takamura H, Yamashita H
    • Journal Title

      Jpn J Ophthalmol 54

      Pages: 74-80

    • NAID

      10027203554

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      阿部さち、山下英俊
    • Journal Title

      糖尿病最新の治療2010-2012(南江堂)

      Pages: 181-183

    • Related Report
      2009 Annual Research Report
  • [Presentation] ブタ硝子体細胞におけるIL-1刺激によるヒアルロン酸産生制御の検討2012

    • Author(s)
      柏木佳子, 西塚弘一, 山下英俊
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Year and Date
      2012-04-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] シンポジウム「糖尿病黄斑浮腫の薬物治療-新たな可能性と問題点」ステロイド眼局所治療の展望2011

    • Author(s)
      後藤早紀子
    • Organizer
      第65回日本臨床眼科学会総会(シンポジスト)
    • Place of Presentation
      東京東京国際フォーラム
    • Year and Date
      2011-10-08
    • Related Report
      2011 Final Research Report
  • [Presentation] シンポジウム「糖尿病黄斑浮腫の薬物治療-新たな可能性と問題点」ステロイド眼局所治療の展望2011

    • Author(s)
      後藤早紀子
    • Organizer
      第65回日本臨床眼科学会総会
    • Place of Presentation
      東京国際フォーラム(東京)(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] ブタ硝子体細胞におけるIL-1刺激によるヒアルロン酸産生制御の検討2010

    • Author(s)
      柏木佳子, 西塚弘一, 山下英俊
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京東京国際フォーラム
    • Year and Date
      2010-04-05
    • Related Report
      2011 Final Research Report
  • [Presentation] 糖尿病黄斑浮腫に対するステロイド点眼治療の長期経過2010

    • Author(s)
      後藤早紀子, 山本禎子, 桐井枝里子, 阿部さち, 山下英俊
    • Organizer
      第49回日本網膜硝子体学会
    • Place of Presentation
      大阪、大阪国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] 糖尿病黄斑浮腫に対するステロイド点眼治療の長期経過2010

    • Author(s)
      後藤早紀子、山本禎子、桐井枝里子、阿部さち、山下英俊
    • Organizer
      第49回日本網膜硝子体学会
    • Place of Presentation
      大阪市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 糖尿病黄斑浮腫における網膜-硝子体界面病態の3次元的画像観察2009

    • Author(s)
      阿部さち, 山本禎子, 中野早紀子, 桐井枝里子, 柏木佳子, 山下英俊
    • Organizer
      第113回日本眼科学会総会
    • Place of Presentation
      東京東京国際フォーラム
    • Year and Date
      2009-04-17
    • Related Report
      2011 Final Research Report
  • [Presentation] 糖尿病黄斑浮腫における網膜-硝子体界面病態の3次元的画像観察2009

    • Author(s)
      阿部さち、山本禎子、中野早紀子、桐井枝里子、柏木佳子、山下英俊
    • Organizer
      第113回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Related Report
      2009 Annual Research Report
  • [Book] 糖尿病最新の治療2010-20122009

    • Author(s)
      阿部さち, 山下英俊
    • Publisher
      南江堂
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 黄斑浮腫治療用点眼剤2010

    • Inventor(s)
      山下英俊, 中野早紀子, 山本禎子, 他
    • Industrial Property Rights Holder
      山形大学
    • Filing Date
      2010-07-14
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 黄斑浮腫治療用点眼剤2010

    • Inventor(s)
      山下英俊、藤早紀子、山本禎子、阿部さち、桐井枝里子
    • Industrial Property Rights Holder
      山下英俊、藤早紀子、山本禎子、阿部さち、桐井枝里子
    • Filing Date
      2010-07-14
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 黄斑浮腫治療用点眼剤2009

    • Inventor(s)
      山下英俊、中野早紀子、山本禎子, 他
    • Industrial Property Rights Holder
      山形大学
    • Filing Date
      2009-07-14
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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