Title:Guanabenz and Clonidine, α2-Adrenergic Receptor Agonists, Inhibit Choroidal Neovascularization
Volume: 18
Issue: 1
Author(s): Miruto Tanaka, Yuki Inoue, Takahiko Imai, Norifumi Tanida, Koichi Takahashi and Hideaki Hara*
Affiliation:
- Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu,Japan
Keywords:
Age-related macular degeneration, α2-adrenergic receptor agonist, choroidal neovascularization, guanabenz, clonidine,
retinal endothelial cells, vascular endothelial growth factor.
Abstract:
Background: Neovascular age-related macular degeneration (AMD) with choroidal neovascularization
(CNV) is a leading cause of blindness in elderly people. Anti-vascular endothelial
growth factor (anti-VEGF)-drugs are used to treat AMD patients; however, some patients are resistant
to these therapies.
Objective: The purpose of this study was to investigate the anti-angiogenic effects of α2-adrenergic
agonists, including guanabenz and clonidine.
Methods: We evaluated the anti-angiogenic effects of α2-adrenergic agonists in human retinal microvascular
endothelial cells (HRMECs). A proliferation assay was conducted, and the migration
ratio was evaluated. In a laser-induced CNV model, guanabenz and clonidine were delivered via intraperitoneal
injection or implantation of an osmotic pump device. Fourteen days following CNV
induction, CNV lesion size and fundus fluorescein angiography (FFA) were evaluated.
Results: Guanabenz and clonidine inhibited VEGF-induced retinal endothelial cell growth and migration.
In the CNV model mice, CNV lesion sizes were reduced by intraperitoneal administration
of guanabenz or clonidine. Data, including body weight, systolic blood pressure, and heart rate
showed that guanabenz (0.5 and 2.0 mg/kg/day) had little effect on these parameters; conversely, a
high dose of clonidine (1.0 mg/kg/day) did affect these parameters. Additionally, clonidine did not
affect CNV size, but continuous administration of guanabenz attenuated both CNV size and leakage
from neovessels.
Conclusion: Our study suggests a key role for α2-adrenergic receptors during CNV formation.
Therefore, we suggest that α2-adrenergic receptor agonists may represent novel therapeutic drugs
for patients with neovascular AMD.
