PMID- 25366488
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20211203
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 37
IP  - 11
DP  - 2014
TI  - Anti-angiogenic effects of mammalian target of rapamycin inhibitors in a mouse 
      model of oxygen-induced retinopathy.
PG  - 1838-42
AB  - 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.
FAU - Yagasaki, Rina
AU  - Yagasaki R
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences.
FAU - Nakahara, Tsutomu
AU  - Nakahara T
FAU - Ushikubo, Hiroko
AU  - Ushikubo H
FAU - Mori, Asami
AU  - Mori A
FAU - Sakamoto, Kenji
AU  - Sakamoto K
FAU - Ishii, Kunio
AU  - Ishii K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Angiogenesis Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - S88TT14065 (Oxygen)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Angiogenesis Inhibitors/pharmacology/*therapeutic use
MH  - Animals
MH  - Everolimus
MH  - Mice, Inbred ICR
MH  - Oxygen
MH  - Retina/drug effects/metabolism/pathology
MH  - Retinal Neovascularization/*drug therapy/etiology/metabolism
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Sirolimus/*analogs & derivatives/pharmacology/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2014/11/05 06:00
MHDA- 2015/06/30 06:00
CRDT- 2014/11/05 06:00
PHST- 2014/11/05 06:00 [entrez]
PHST- 2014/11/05 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
AID - DN/JST.JSTAGE/bpb/b14-00487 [pii]
AID - 10.1248/bpb.b14-00487 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2014;37(11):1838-42. doi: 10.1248/bpb.b14-00487.