PMID- 30409713
OWN - NLM
STAT- MEDLINE
DCOM- 20190114
LR  - 20190114
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 138
IP  - 3
DP  - 2018 Nov
TI  - Anti-angiogenic effects of valproic acid in a mouse model of oxygen-induced 
      retinopathy.
PG  - 203-208
LID - S1347-8613(18)30189-0 [pii]
LID - 10.1016/j.jphs.2018.10.004 [doi]
AB  - Pathological retinal angiogenesis contributes to the pathogenesis of several 
      ocular diseases. Valproic acid, a widely used antiepileptic drug, exerts 
      anti-angiogenic effects by inhibiting histone deacetylase (HDAC). Herein, we 
      investigated the effects of valproic acid and vorinostat, a HDAC inhibitor, on 
      pathological retinal angiogenesis in mice with oxygen-induced retinopathy (OIR). 
      OIR was induced in neonatal mice by exposure to 80% oxygen from postnatal day (P) 
      7 to P10 and to atmospheric oxygen from P10 to P15. Mice were subcutaneously 
      injected with valproic acid, vorinostat, or vehicle once a day from P10 to P14. 
      At P15, retinal neovascular tufts and vascular growth in the central avascular 
      zone were observed in mice with OIR. Additionally, immunoreactivity for 
      phosphorylated ribosomal protein S6 (pS6), an indicator of mammalian target of 
      rapamycin (mTOR) activity, was detected in the neovascular tufts. Both valproic 
      acid and vorinostat reduced the formation of retinal neovascular tuft without 
      affecting vascular growth in the central avascular zone. Valproic acid reduced 
      the pS6 immunoreactivity in neovascular tufts. Given that vascular endothelial 
      growth factor (VEGF) activates mTOR-dependent pathways in proliferating 
      endothelial cells of the neonatal mouse retina, these results suggest that 
      valproic acid suppresses pathological retinal angiogenesis by interrupting 
      VEGF-mTOR pathways.
CI  - Copyright (c) 2018 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Iizuka, Naoto
AU  - Iizuka N
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; 
      Pharmacy Practice and Science II (Kitasato University East Hospital), Kitasato 
      University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 
      108-8641, Japan.
FAU - Morita, Akane
AU  - Morita A
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
FAU - Kawano, Chihiro
AU  - Kawano C
AD  - Pharmacy Practice and Science II (Kitasato University East Hospital), Kitasato 
      University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 
      108-8641, Japan.
FAU - Mori, Asami
AU  - Mori A
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
FAU - Sakamoto, Kenji
AU  - Sakamoto K
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
FAU - Kuroyama, Masakazu
AU  - Kuroyama M
AD  - Pharmacy Practice and Science II (Kitasato University East Hospital), Kitasato 
      University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 
      108-8641, Japan.
FAU - Ishii, Kunio
AU  - Ishii K
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
FAU - Nakahara, Tsutomu
AU  - Nakahara T
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. 
      Electronic address: nakaharat@pharm.kitasato-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20181014
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Ribosomal Protein S6)
RN  - 58IFB293JI (Vorinostat)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Disease Models, Animal
MH  - Mice
MH  - Neovascularization, Pathologic/chemically induced/*prevention & control
MH  - Oxygen/*metabolism
MH  - Phosphorylation
MH  - Retina/*drug effects/metabolism/*pathology
MH  - Retinal Diseases/blood/metabolism/pathology
MH  - Ribosomal Protein S6/metabolism
MH  - Valproic Acid/*pharmacology
MH  - Vorinostat/*pharmacology
OTO - NOTNLM
OT  - Histone deacetylase
OT  - Mammalian target of rapamycin
OT  - Pathological angiogenesis
OT  - Retina
OT  - Vascular endothelial growth factor
EDAT- 2018/11/10 06:00
MHDA- 2019/01/15 06:00
CRDT- 2018/11/10 06:00
PHST- 2018/08/15 00:00 [received]
PHST- 2018/09/20 00:00 [revised]
PHST- 2018/10/10 00:00 [accepted]
PHST- 2018/11/10 06:00 [pubmed]
PHST- 2019/01/15 06:00 [medline]
PHST- 2018/11/10 06:00 [entrez]
AID - S1347-8613(18)30189-0 [pii]
AID - 10.1016/j.jphs.2018.10.004 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2018 Nov;138(3):203-208. doi: 10.1016/j.jphs.2018.10.004. Epub 
      2018 Oct 14.