title: Suppression of choroidal neovascularization by vasohibin-1, a vascular endothelium-derived angiogenic inhibitor.
abstract: PURPOSE. To determine the expression of vasohibin-1 during the development of experimentally induced choroidal neovascularization (CNV) and to investigate the effect of vasohibin-1 on the generation of CNV. METHODS. CNV lesions were induced in the eyes of wild-type (WT) and vasohibin-1 knockout (KO) mice by laser photocoagulation. The expression of vasohibin-1, vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR1), VEGFR2, and pigment epithelial-derived factor (PEDF) was determined by semiquantitative reverse transcription-polymerase chain reaction. The expression of vasohibin-1 was also examined by immunohistochemistry with anti-CD68, anti-alpha smooth muscle actin (αSMA), anti-cytokeratin, and anti-CD31. Vasohibin-1 was injected into the vitreous and the activity and size of the CNV were determined by fluorescein angiography and in choroidal flat mounts. RESULTS. Vasohibin-1 was detected not only in CD31-positive endothelial cells but also in CD68-positive macrophages and αSMA-positive retinal pigment epithelial cells. Strong vasohibin-1 expression was observed at day 28, when the CNV lesions had regressed by histologic examination. The vasohibin-1 level was significantly decreased at day 14 and increased at day 28 after laser application. Significantly less VEGFR2 expression was observed on day 4 after vasohibin-1. The expression of PEDF was not significantly changed by vasohibin-1 injection. Vasohibin-1 injection significantly suppressed the CNV, with no adverse side effects. The CNV lesions in the vasohibin-1-KO mice were significantly larger than those in the WT mice. CONCLUSIONS. The endogenous expression of vasohibin-1 is associated with the natural course of the development of CNV. Intravitreal injections of vasohibin-1 may be a method for inhibiting CNV.
authors.affiliation: Division of Clinical Cell Therapy, Center for Advanced Medical Research and Development, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Wakusawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Abe
authors.forename: Hajime
authors.initials: H
authors.lastname: Sato
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sonoda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Mitsuda
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Takakura
authors.forename: Tomi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Onami
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nagai
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishida
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000199:Actins / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000494:pharmacology*; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005451:Fluorescein Angiography; D005786:Gene Expression Regulation / Q000502:physiology; D058449:Intravitreal Injections; D007633:Keratins / Q000378:metabolism; D017075:Laser Coagulation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D000199:Actins; D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D018797:Cell Cycle Proteins; D005136:Eye Proteins; D007633:Keratins; D009414:Nerve Growth Factors; D011993:Recombinant Fusion Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099174:Pigment Epithelium-Derived Factor; C493181:VASH1 protein, human; C510089:Vash1 protein, mouse; C544013:alpha-smooth muscle actin, mouse; C467480:vascular endothelial growth factor A, mouse