Deguelin inhibits retinal neovascularization by down-regulation of HIF-1alpha in oxygen-induced retinopathy.
Retinal neovascularization is the most common cause of blindness; Retinopathy of pre-maturity (ROP) for children and diabetic retinopathy for young age group. ROP still remains as the most serious cause of vision loss in children. We provided that deguelin significantly reduces retinal neovascularization in a mouse model of ROP. Deguelin never affected the transcriptional activity of hypoxia inducible factor (HIF)-1, however, reduced HIF-1 expression, which led to the decrease of vascular endothelial growth factor expression. Deguelin effectively suppressed endothelial cell proliferation without cytotoxic effect under therapeutic concentration range. In addition, deguelin demonstrated no reduction or retardation in normal retinal development and no retinal toxicity. These data suggest deguelin is a potent inhibitor of retinal neovascularization and may be applied in the treatment of other vasoproliferative retinopathies.
Kim
J H
JH
Department of Ophthalmology, College of Medicine, Seoul National University & Seoul Artifical Eye Center Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Kim
J H
JH
Yu
Y S
YS
Shin
J Y
JY
Lee
H-Y
HY
Kim
K-W
KW
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects; D012178:Retinopathy of Prematurity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012402:Rotenone; C107676:deguelin; D010100:Oxygen