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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; Suppression of Choroidal Neovascularization by Vasohibin-1, a Vascular Endothelium–Derived Angiogenic Inhibitor. Invest. Ophthalmol. Vis. Sci. 2011;52(6):3272-3280. doi: https://doi.org/10.1167/iovs.10-6295.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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