Suppression of choroidal neovascularization by vasohibin-1, a vascular endothelium-derived angiogenic inhibitor

Ryosuke Wakusawa, Toshiaki Abe, Hajime Sato, Hikaru Sonoda, Masaaki Sato, Yuuichi Mitsuda, Tomoaki Takakura, Tomi Fukushima, Hideyuki Onami, Nobuhiro Nagai, Yumi Ishikawa, Kohji Nishida, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3272-3280
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Issue number6
Publication statusPublished - 2011 May


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