Anti-angiogenic Effects of Mammalian Target of Rapamycin Inhibitors in a Mouse Model of Oxygen-Induced Retinopathy

• Yagasaki Rina

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Nakahara Tsutomu

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Ushikubo Hiroko

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Mori Asami

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Sakamoto Kenji

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Ishii Kunio

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

抄録

Ocular pathologic angiogenesis is a causative factor for retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. In the present study, we examined the effects of rapamycin and everolimus, inhibitors of mammalian target of rapamycin (mTOR), on retinal pathologic angiogenesis in mice with oxygen-induced retinopathy (OIR), an animal model of proliferative ischemic retinopathy. Mice were exposed to 80% oxygen from postnatal day (P) 7 to P10, and were then brought into room air and subcutaneously injected with rapamycin and everolimus. The neovascular tufts, the size of the central avascular zone, and the immunoreactivity for phosphorylated ribosomal protein S6 (pS6), a downstream indicator of mTOR activity, were evaluated in flat-mounted retinas. Retinal neovascular tufts and vascular growth in the avascular zone were observed in P15 mice with OIR. In addition, intense immunoreactivity for pS6 was detected in the neovascular tufts and in endothelial cells located at the vascular–avascular border. Both rapamycin and everolimus reduced the extent of retinal neovascular tufts and pS6 immunoreactivity, but they also increased the size of the avascular zone. Thus, activation of the mTOR pathway in endothelial cells contributes to retinal pathologic angiogenesis, and mTOR inhibitors that target proliferating endothelial cells are promising candidates as anti-angiogenic agents for the treatment of vasoproliferative retinal diseases.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 37 (11), 1838-1842, 2014

  公益社団法人 日本薬学会

キーワード

• mammalian target of rapamycin
• pathologic angiogenesis
• retina
• vascular endothelial growth factor

詳細情報

• CRID: 1390282679610506752
• NII論文ID: 130004703901
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00487
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 025880604
• PubMed: 25366488
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I025880604
• Web Site: https://www.jstage.jst.go.jp/article/bpb/37/11/37_b14-00487/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015248468
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可