Suppression of Choroidal Neovascularization by Intravitreal Vasohibin-1 in Monkey Eyes

Abstract

Purpose: : To investigate the effect of vasohibin-1 for suppression of choroidal neovascularization (CNV) in monkey eyes.

Methods: : A CNV was induced in monkey eyes by laser photocoagulations. The laser settings were; 50 micrometer diameter, 0.1 sec duration, and 650-750 mW intensity. Three monkeys were evaluated for the safety of the injections, six monkeys for dose effects of a single injection, and three monkeys for repeated injections of vasohibin-1. Ophthalmoscopy, fluorescein angiography, focal electroretinograms (ERGs), and optical coherent tomography (OCT) were used to evaluate the retinas. The level of vascular endothelial growth factor (VEGF) in the aqueous was determined by ELISA. Immunohistochemistry was used to determine the site of vasohibin-1 and cytokeratin expression.

Results: : An intravitreal injection of more than 10 µg of vasohibin-1 induced mild intraocular inflammation. Eyes with an intravitreal injection of 0.1 and 1.0 µg of vasohibin-1 had significant less fluorescein leakage and larger amplitude focal electroretinograms (ERGs) than that of vehicle-injected eyes. Similar results were obtained by repeated injections of 0.1 of vasohibin-1 by OCT and focal ERG. Immunohistochemistry showed that vasohibin-1 was expressed mainly in the ECs of the vessels of the CNV. Cytokeratin was detected to cover the CNV, especially in vassohibin-1 treated monkey eyes. The VEGF level in the aqueous was not significantly altered by the vasohibin-1.

Conclusions: : Intravitreal vaohibin-1 significantly reduces the grade of the laser-induced CNVs with preservation of the macular function in monkeys. Vasohibin-1 may alter the course of CNV without affecting VEGF.

Keywords: age-related macular degeneration • neovascularization