Inhibition of choroidal neovascularization by homoisoflavanone, a new angiogenesis inhibitor.
OBJECTIVE
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly. The detailed mechanism of choroidal neovascularization (CNV) leads to severe vision loss in patients with AMD. This study was undertaken to evaluate the inhibitory effect of homoisoflavanone on CNV.


METHODS
Antiangiogenic activity of homoisoflavanone was evaluated by in vitro tube formation assay of human umbilical vein endothelial cells (HUVECs) and cell migration assay of HUVECs., Homoisoflavanone or PBS was injected intravitreously into a mouse model of laser-photocoagulation-induced CNV. Fluorescein angiography and vessel counting in cross sections were employed to examine CNV lesions. The toxicity of homoisoflavanone was evaluated through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) assay in HUVECs as well as histological examination and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining in the retina.


RESULTS
Homoisoflavanone effectively inhibited in vitro tube formation and cell migration of HUVECs. Interestingly, homoisoflavanone significantly reduced CNV and its leakage in a mouse model of laser-photocoagulation-induced CNV. In addition, homoisoflavanone showed no effect on cell viability of HUVECs and no retinal toxicity in a concentration range of 1-10 microM.


CONCLUSIONS
Our data suggest that homoisoflavanone is a potent inhibitor of CNV and may be applied in the treatment of other vasoproliferative retinopathies and tumor.
Kim
Jeong Hun
JH
Department of Ophthalmology, College of Medicine, Seoul National University, Seoul Artificial Eye Center Clinical ResearchInstitute, Seoul National University Hospital, Seoul, Korea.
Kim
Jin Hyoung
JH
Yu
Young Suk
YS
Jun
Hyoung-Oh
HO
Kwon
Ho Jeong
HJ
Park
Kyu Hyung
KH
Kim
Kyu-Won
KW
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D017075:Laser Coagulation; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000187:drug effects
C524883:5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one; D020533:Angiogenesis Inhibitors; D007529:Isoflavones