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

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3272-3280
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number6
DOIs
Publication statusPublished - 2011 May

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Wakusawa, R., Abe, T., Sato, H., Sonoda, H., Sato, M., Mitsuda, Y., Takakura, T., Fukushima, T., Onami, H., Nagai, N., Ishikawa, Y., Nishida, K., & Sato, Y. (2011). Suppression of choroidal neovascularization by vasohibin-1, a vascular endothelium-derived angiogenic inhibitor. Investigative Ophthalmology and Visual Science, 52(6), 3272-3280. https://doi.org/10.1167/iovs.10-6295