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

AIM: The effects of Guanabenz, an agonist of α2-adrenergic receptors routinely used in human medicine as an antihypertensive drug, were studied on NaIO(3)-induced retinal pigment epithelium (RPE) degeneration, laser-induced choroidal neovascularization (CNV) and choroidal blood flow, in animal models. METHODS: The 35mg/kg NaIO(3)-induced RPE degeneration rat eyes were instilled with 1% Guanabenz eye drops 3 times a day for 7 days before NaIO(3) 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 NaIO(3) injection, the amplitude of ERG c-wave was 0.422±0.092 millivolts in the control group, 0.103±0.04 millivolts in the NaIO(3) group, and 0.254±0.061 millivolts in the Guanabenz+NaIO(3) group. There was a significant protection of the ERG c-wave by Guanabenz as compared to NaIO(3) 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 mm(2) in the control group, and 1.24±0.16 mm(2) 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 NaIO(3)-induced degeneration, inhibited the development of CNV in laser-induced rat AMD model and increased choroidal blood flow markedly in vivo.