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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Guanabenz and Clonidine, α2-Adrenergic Receptor Agonists, Inhibit Choroidal Neovascularization

Author(s): Miruto Tanaka, Yuki Inoue, Takahiko Imai, Norifumi Tanida, Koichi Takahashi and Hideaki Hara*

Volume 18, Issue 1, 2021

Published on: 13 July, 2021

Page: [85 - 92] Pages: 8

DOI: 10.2174/1567202618666210518133634

Price: $65

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.

Keywords: Age-related macular degeneration, α2-adrenergic receptor agonist, choroidal neovascularization, guanabenz, clonidine, retinal endothelial cells, vascular endothelial growth factor.

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