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Molecular basis for the homeostatic mechanisms that maintain retinal blood vessels and the application for development of anti-glaucoma drugs

Research Project

Project/Area Number 20590090
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKitasato University

Principal Investigator

NAKAHARA Tsutomu  Kitasato University, 薬学部, 准教授 (10296519)

Co-Investigator(Kenkyū-buntansha) MORI Asami  北里大学, 薬学部, 助教 (80453504)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords薬理学 / 血管生物学 / 微小循環
Research Abstract

It has been suggested that an impairment of retinal circulation contributes to the onset and progression of glaucoma. This study demonstrates that retinal blood vessels are damaged structurally and functionally in rat models of retinal degeneration induced by the retinal ischemia-reperfusion and by an intravitreal injection of NMDA. In these models, changes in retinal layer are limited in the inner retina as demonstrated by loss of retinal ganglion cells and thinning of inner plexiform layer. Therefore, it is likely that neuronal cells presented in the inner retina play a role in maintaining the vascular structure through production/release of growth factors and trophic factors for vascular cells. For example, in this study, we found that retinal ganglion cells express vascular endothelial growth factor (VEGF) in rat retina. The loss of retinal ganglion cells that are one of sources of VEGF in the retina may fail to provide sufficient amounts of VEGF for maintaining the vascular structure and function. Thus, neuronal cell damage may be an additional cause of progression of the retinal damage by reducing blood supply to retinal neurons. The protection of retinal vascular structure and function would be a novel strategy for preventing progression of glaucoma.

Report

(3 results)
  • 2010 Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (17 results)

All 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 3 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] Ishii K Role of calcium-activated potassium channels in acetylcholine-induced vasodilation of rat retinal arterioles in vivo2011

    • Author(s)
      Mori A, Suzuki S, Sakamoto K, Nakahara T
    • Journal Title

      Naunyn-Schmiedeberg's Arch Pharmacol. 383(1)

      Pages: 27-34

    • Related Report
      2010 Final Research Report
  • [Journal Article] Retinal blood vessels are damaged in a rat model of NMDA-induced retinal degeneration2010

    • Author(s)
      Ueda K, Nakahara T, Hoshino M, Mori A, Sakamoto K, Ishii K.
    • Journal Title

      Neurosci Lett. Nov12;485(1)

      Pages: 55-59

    • Related Report
      2010 Final Research Report
  • [Journal Article] Pharmacological evidence for the presence of functional ?3-adrenoceptors in rat retinal blood vessels2010

    • Author(s)
      Mori A, Miwa T, Sakamoto K, Nakahara T, Ishii K.
    • Journal Title

      Naunyn-Schmiedeberg's Arch Pharmacol. 382(2)

      Pages: 119-126

    • Related Report
      2010 Final Research Report
  • [Journal Article] Hyperglycemia impairs acetylcholine-induced vasodilation of retinal arterioles through polyol pathway-independent mechanisms in rats.2010

    • Author(s)
      Mori A, Saigo O, Sakamoto K, Nakahara T, Ishii K.
    • Journal Title

      J Pharmacol Sci. 112(3)

      Pages: 336-342

    • NAID

      10027744548

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nitric oxide dilates rat retinal blood vessels by cyclooxygenase-dependent mechanisms2009

    • Author(s)
      Ogawa N, Mori A, Hasebe M, Hoshino M, Saito M, Sakamoto K, Nakahara T, Ishii K.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 297(4)

    • Related Report
      2010 Final Research Report
  • [Journal Article] Hyperglycemia impairs acetylcholine-induced vasodilation of retinal arterioles through polyol pathway-independent mechanisms in rats2009

    • Author(s)
      Mori A, Saigo O, Sakamoto K, Nakahara T, Ishii K.
    • Journal Title

      J Pharmacol Sci. 110(2)

      Pages: 160-168

    • NAID

      10027744548

    • Related Report
      2010 Final Research Report
  • [Journal Article] Nitric oxide dilates rat retinal blood vessels by cyclooxygenase-dependent mechanisms.2009

    • Author(s)
      Ogawa N, Mori A, Hasebe M, Hoshino M, Saito M, Sakamoto K, Nakahara T, Ishii K.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 297(4)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperglycemia accelerates impairment of vasodilator responses to acetyl choline of retinal blood vessels in rats.2009

    • Author(s)
      Mori A, Saigo O, Hanada M, Nakahara T, Ishii K.
    • Journal Title

      J Pharmacol Sci. 110(2)

      Pages: 160-168

    • NAID

      10025737064

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ラット網膜神経障害モデルにおけるTGF-? 阻害薬の網膜血管保護効果2011

    • Author(s)
      植田香、中原努、森麻美、坂本謙司、石井邦雄
    • Organizer
      第84回日本薬理学会年会
    • Year and Date
      2011-03-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 緑内障モデルラットにおいて観察される網膜血管の構造的・機能的変化2010

    • Author(s)
      植田香、中原努、森麻美、坂本謙司、石井邦雄
    • Organizer
      第11回Pharmaco-Hematology シンポジウム
    • Year and Date
      2010-06-18
    • Related Report
      2010 Final Research Report
  • [Presentation] NMDA 硝子体内投与による網膜血管傷害の誘導2010

    • Author(s)
      植田香、中原努、森麻美、坂本謙司、石井邦雄
    • Organizer
      第83回日本薬理学会年会
    • Year and Date
      2010-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] NMDA硝子体内投与による網膜血管傷害の誘導2010

    • Author(s)
      植田香、中原努、森麻美、坂本謙司、石井邦雄
    • Organizer
      日本薬理学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 緑内障モデルラットを用いた網膜血管の構造・機能維持機構の解析2009

    • Author(s)
      中原努、星野真耶、星野真一郎、植田香、森麻美、坂本謙司、石井邦雄
    • Organizer
      生体機能と創薬シンポジウム2009
    • Year and Date
      2009-08-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 緑内障モデルラットを用いた網膜血管の構造・機能維持機構の解析2009

    • Author(s)
      中原努、星野真耶、星野真一郎、植田香、森麻美、坂本謙司、石井邦雄
    • Organizer
      日本薬学会
    • Place of Presentation
      東京
    • Year and Date
      2009-08-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] 網膜血管のペリサイトに及ぼす虚血再灌流の影響2009

    • Author(s)
      星野真耶、中原努、石井邦雄
    • Organizer
      第82回日本薬理学会年会
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] 網膜血管のペリサイトに及ぼす虚血再濯流の影響2009

    • Author(s)
      星野真耶, 中原努, 石井邦雄
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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