Persistent Intracellular Signaling Pathway as a Promising Therapeutic Target for Retinopathy of Prematurity

• Project/Area Number: 15K20260
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Osaka University
• Principal Investigator: Fukushima Yoko 大阪大学, 医学系研究科, 助教 (70647031)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); 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: 血管新生 / 内皮細胞 / 細胞内シグナル伝達分子 / 網膜 / 細胞内シグナル伝達 / VEGF

Outline of Final Research Achievements

Retinopathy of prematurity (ROP) is a vision-threatening disease in the retina of premature infants with incomplete retinal vascularization. In ROP, retinal vascular development stops and subsequently disorganized, fragile and leaky blood vessels grow. It has been studied that VEGF plays a critical role in the development of ROP. However, it remains unknown how endothelial cells alter responses to identical VEGF signaling in the growth of abnormal blood vessels. Here, we focused on long-lasting VEGF stimulation to reflect pathological condition, which induced persistent phosphorylation of Akt in cultured endothelial cells. Retinal blood vessels were dilated and leaky by the activation of Akt signaling pathway with transgenic mice. Therefore, molecules regulating persistent Akt activation can be potential targets for the treatment of ROP.

Research Products

• [Journal Article] Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown (2017)
  • Author(s): Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, Fukushima Y, Nara H, Sakai H, Fujiwara T, Matsushita J, Ema M, Hirashima M, Minami T, Shibuya M, Takakura N, Kim P, Miyata T, Ogura Y, Uemura A
  • Journal Title: JCI Insight Volume: 2 Issue: 3
  • DOI: 10.1172/jci.insight.90905
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Electroretinographic effects of retinal dragging and retinal folds in eyes with familial exudative vitreoretinopathy. (2016)
  • Author(s): Yaguchi Y, Katagiri S, Fukushima Y, Yokoi T, Nishina S, Kondo M, Azuma N.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 30523-30523
  • DOI: 10.1038/srep30523
  • Peer Reviewed / Open Access
• [Journal Article] Semaphorin 3G provides a repulsive guidance cue to lymphatic endothelial cells via Neuropilin-2/PlexinD1. (2016)
  • Author(s): Liu X, Uemura A, Fukushima Y, Yoshida Y, Hirashima M.
  • Journal Title: Cell Rep Volume: 17 Issue: 9 Pages: 2299-2311
  • DOI: 10.1016/j.celrep.2016.11.008
  • NAID: 120005970748
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] インストラクションコース 未熟児網膜症アップデート (2016)
  • Author(s): 福嶋葉子
  • Organizer: 第70回 臨床眼科学会
  • Place of Presentation: 京都
  • Year and Date: 2016-11-03
• [Presentation] 未熟児網膜症アップデート（インストラクションコース） (2015)
  • Author(s): 福嶋葉子
  • Organizer: 第69回 臨床眼科学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-22
• [Presentation] 虚血性網膜症における異常血管新生を誘導する新たなシグナル伝達機構の解析 (2015)
  • Author(s): 福嶋葉子
  • Organizer: 第６回 Molecular Cardivascular Conference 2
  • Place of Presentation: ヒルトン福岡 シーホーク
  • Year and Date: 2015-09-04
• [Book] 今日の眼疾患治療指針 第3版 「未熟児網膜症」「第一次硝子体過形成遺残」 (2016)
  • Author(s): 福嶋葉子
  • Publisher: 医学書院
• [Book] 眼科グラフィック (ROPに対する抗VEGF療法) (2015)
  • Author(s): 福嶋葉子
  • Total Pages: 216
  • Publisher: メディカ出版
• [Book] 小児眼科学 (分担執筆: 眼疾患を伴う全身症候群) (2015)
  • Author(s): 福嶋葉子
  • Total Pages: 567
  • Publisher: 三輪書店