Pathophysiological function of calcitonin gene-related peptide in ocular inflammatory diseases.

• Project/Area Number: 15H06244
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Shinshu University
• Principal Investigator: TORIYAMA Yuichi 信州大学, 医学部, 助教(特定雇用) (90757759)
• Research Collaborator: SHINDO Takayuki (MURATA Toshinori) 信州大学, 学術研究院医学系, 教授 (50253406) ; IMAI Akira 信州大学, 大学院医学系研究科, 大学院生 ; HIRABAYASHI Kazutaka 信州大学, 大学院医学系研究科, 大学院生
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: カルシトニン遺伝子関連ペプチド / アドレノメデュリン / 網膜 / 神経保護 / 血管透過性 / 眼内炎症 / ぶどう膜炎

Outline of Final Research Achievements

Because the LPS-induced uveitis model did not work well, we tried to explore other models. In Kimba mice, which overexpress human vascular endothelial growth factor in their retinas, the capillary dropout, vascular leakage, and vascular fragility characteristic of diabetic retinopathy were observed. Intravitreal or systemic administration of ADM to Kimba mice ameliorated both the capillary dropout and vascular leakage. Evaluation of the transendothelial electrical resistance and fluorescein isothiocyanate-dextran permeability of an endothelial cell monolayer using TR-iBRB retinal capillary endothelial cells revealed that vascular endothelial growth factor enhanced vascular permeability but that co-administration of ADM suppressed the effect, in part by enhancing tight junction formation between endothelial cells. AM could serve as a novel therapeutic agent for the treatment of diabetic retinopathy.

Research Products

• [Journal Article] Adrenomedullin Suppresses Vascular Endothelial Growth Factor-Induced Vascular Hyperpermeability and Inflammation in Retinopathy. (2017)
  • Author(s): Imai A, Toriyama Y, Iesato Y, Hirabayasi K, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Liu T, Xian X, Zhai L, Dai K, Tanimura K, Liu T, Cui N, Yamauchi A, Murata T, Shindo T
  • Journal Title: American journal of Pathology Volume: 187(5) Issue: 5 Pages: 999-1015
  • DOI: 10.1016/j.ajpath.2017.01.014
  • Peer Reviewed
• [Presentation] Adrenomedullin Suppresses VEGF-induced Vascular hyperpermeability and Inflammation in Retinopathy (2017)
  • Author(s): 今井 章、鳥山 佑一、家里 康弘、平林 一貴、村田 敏規、新藤 隆行ほか
  • Organizer: 第81回日本循環器学会学術総会
  • Place of Presentation: 金沢市教育プラザ此花
  • Year and Date: 2017-03-19