Role of retinal neuronal cells in the architecture and functional regulation of retinal blood vessels

• Project/Area Number: 15K08242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kitasato University
• Principal Investigator: Mori Asami 北里大学, 薬学部, 助教 (80453504)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 微小循環 / 緑内障 / 血管生物学 / 網膜血管 / 網膜神経‐グリア‐血管連関 / 一酸化窒素 / プロスタグランジン / 薬理学 / 神経‐グリア‐血管連関 / NO / 網膜神経

Outline of Final Research Achievements

The purpose of this study was to investigate interactions between blood vessels and neuronal cells in the retina. Intravitreal injection of low dose of NMDA (6 nmol) facilitated neuronal nitric oxide (NO) synthase-derived NO production in retinal ganglion and amacrine cells. NO released from neuronal cells acted on retinal glial cells, thereby dilating retinal blood vessels. Intravitreal injection of high dose of NMDA (200 nmol) induced damage to retinal neuronal cells and blood vessels. In the injured retina, NMDA (6 nmol)-induced vasodilation was mediated by inducible NO synthase-derived NO. These results suggest that NO released from neuronal and glial cells plays an important role in the vasodilatory mechanisms of blood vessels in the retina.

Research Products

• [Journal Article] Methylglyoxal Impairs β₂-Adrenoceptor-Mediated Vasodilatory Mechanisms in Rat Retinal Arterioles (2018)
  • Author(s): Akagawa M, Mori A, Sakamoto K, Nakahara T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 41 Issue: 2 Pages: 272-276
  • DOI: 10.1248/bpb.b17-00861
  • NAID: 130006329275
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Stimulation of β₁- and β₂-adrenoceptors dilates retinal blood vessels in rats (2017)
  • Author(s): Mori A, Sekito A, Sakamoto K, Ishii K, Nakahara T
  • Journal Title: Naunyn Schmiedebergs Arch Pharmacol Volume: 390 Issue: 5 Pages: 527
  • DOI: 10.1007/s00210-017-1349-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Stimulation of μ-opioid receptors dilates retinal arterioles by neuronal nitric oxide synthase-derived nitric oxide in rats (2017)
  • Author(s): Someya E, Mori A, Sakamoto K, Ishii K, Nakahara T
  • Journal Title: Eur J Pharmacol Volume: 803 Pages: 124
  • DOI: 10.1016/j.ejphar.2017.03.043
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Probucol prevents the attenuation of β₂-adrenoceptor-mediated vasodilation of retinal arterioles in diabetic rats (2017)
  • Author(s): Mori A, Higashi K, Wakao S, Sakamoto K, Ishii K, Nakahara T.
  • Journal Title: Naunyn Schmiedebergs Arch Pharmacol. Volume: 390 Issue: 12 Pages: 1247
  • DOI: 10.1007/s00210-017-1423-y
  • Peer Reviewed
• [Journal Article] Role of Glial Cells in μ-Opioid Receptor-Mediated Vasodilation in the Rat Retina (2017)
  • Author(s): Someya E, Mori A, Asano D, ◎Morita A, Sakamoto K, Nakahara T.
  • Journal Title: Curr. Eye Res. Volume: 43 Issue: 3 Pages: 350
  • DOI: 10.1080/02713683.2017.1403631
  • Peer Reviewed
• [Journal Article] Anti-diabetic drug metformin dilates retinal blood vessels through activation of AMP-activated protein kinase in rats (2017)
  • Author(s): Mori A, Ishikawa E, Amano T, Sakamoto K, Nakahara T
  • Journal Title: Eur J Pharmacol Volume: 798 Pages: 66
  • DOI: 10.1016/j.ejphar.2017.01.003
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 抗糖尿病薬のメトホルミンはラット網膜血管を拡張させる (2017)
  • Author(s): 森 麻美，石川衣里子，天野智世，坂本謙司 ，中原 努
  • Organizer: 第90回日本薬理学会年会（長崎）
  • Place of Presentation: 長崎新聞文化ホール（長崎県長崎市）
  • Year and Date: 2017-03-16
• [Presentation] ラット網膜においてオピオイド μ 受容体刺激は神経由来の NO 産生を介して血管を拡張させる (2017)
  • Author(s): 染谷英理子，森 麻美，坂本謙司，石井邦雄，中原 努
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎新聞文化ホール（長崎県長崎市）
  • Year and Date: 2017-03-15
• [Presentation] ラット網膜において methylglyoxal はアドレナリンβ2 受容体を介する血管拡張機序を障害する (2017)
  • Author(s): 赤川真理、森 麻美、坂本謙司、中原 努
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム 2017（京都）
• [Presentation] ラットにおいてアドレナリン β2 受容体刺激は Gi タンパク質-BKCa チャネル経路の活性化を介して網膜血管を拡張させる (2017)
  • Author(s): 森 麻美，長谷川茉美，谷合歩美，坂本謙司，中原 努
  • Organizer: 第27回日本循環薬理学会（名古屋）
• [Presentation] ラット網膜血管におけるβ1, β2およびβ3-アドレナリン受容体刺激を介する拡張反応 (2016)
  • Author(s): 森 麻美，關戸 茜衣，三輪 朋代，牛久保 裕子，坂本 謙司，中原 努
  • Organizer: 第26回日本循環薬理学会（松本）
  • Place of Presentation: 信州大学医学部附属病院 （長野県松本市）
  • Year and Date: 2016-12-02
• [Presentation] 視覚障害をもたらす眼疾患における網膜循環障害 (2016)
  • Author(s): 森 麻美，牛久保 裕子，坂本 謙司，中原 努
  • Organizer: 生体機能と創薬シンポジウム2016（仙台）
  • Place of Presentation: 東北大学 川内北キャンパス（宮城県仙台市）
  • Year and Date: 2016-07-26
• [Presentation] NO dilates retinal arterioles through COX-1/PGI2/IP receptor signaling mechanisms in rats in vivo. (2016)
  • Author(s): Mori A, Namekawa R, Hasebe M, Saito M, Ushikubo H, Sakamoto K, Nakahara T, Ishii K
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜会議センター（神奈川県横浜市）
  • Year and Date: 2016-03-10
• [Presentation] 網膜における神経細胞を介する循環調節機構 (2015)
  • Author(s): 森 麻美，牛久保 裕子，坂本 謙司，中原 努，石井 邦雄
  • Organizer: 第133回日本薬理学会関東部会
  • Place of Presentation: 柏の葉カンファレンスセンター（千葉県柏市）
  • Year and Date: 2015-10-10