RESEARCH ARTICLE


Effect of Guanabenz on Rat AMD Models and Rabbit Choroidal Blood Flow



Yi Shen, Pei Zhuang, George C.Y Chiou*
Institute of Ocular Pharmacology, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843, USA


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© Shen et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Institute of Ocular Pharmacology, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843, USA; Tel: 979-845-2817; Fax: 979-845-0699; E-mail: chiou@medicine.tamhsc.edu


Abstract

Aim:

The effects of Guanabenz, an agonist of α2-adrenergic receptors routinely used in human medicine as an antihypertensive drug, were studied on NaIO3-induced retinal pigment epithelium (RPE) degeneration, laser-induced choroidal neovascularization (CNV) and choroidal blood flow, in animal models.

Methods:

The 35mg/kg NaIO3-induced RPE degeneration rat eyes were instilled with 1% Guanabenz eye drops 3 times a day for 7 days before NaIO3 injection, and then 2 to 4 weeks thereafter. RPE function was measured with c-wave of electroretinogram (ERG). Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch’s membrane. One percent Guanabenz eye drops were given likewise. The development of CNV was determined by fluorescein angiography performed on week 2 and week 4 using sodium fluorescein (FA) or fluorescein isothiocyanatedextran (FD70-FA). Colored microsphere technique was used for in vivo experiments to determine the choroidal blood flow in ocular hypertensive (40 mmHg) rabbit eyes.

Results:

The RPE function was protected significantly by Guanabenz according to the c-wave of ERG. Four weeks after NaIO3 injection, the amplitude of ERG c-wave was 0.422±0.092 millivolts in the control group, 0.103±0.04 millivolts in the NaIO3 group, and 0.254±0.061 millivolts in the Guanabenz+NaIO3 group. There was a significant protection of the ERG c-wave by Guanabenz as compared to NaIO3 group (P<0.01). The angiograms of FD70-FA showed decreased lesion size in the Guanabenz group. Four weeks after laser treatment, the size of the CNV lesion was 2.99±0.18 mm2 in the control group, and 1.24±0.16 mm2 in the Guanabenz group (P<0.01). The choroidal blood flow was significantly increased at 30 and 60 minutes after Guanabenz instillation as compared to corresponding controls.

Conclusions:

Guanabenz significantly protected RPE from NaIO3-induced degeneration, inhibited the development of CNV in laser-induced rat AMD model and increased choroidal blood flow markedly in vivo.

Keywords: Guanabenz, sodium iodate, retinal pigment epithelium, age-related macular degeneration, choroidal blood flow.