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

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.

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.

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.

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.