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Y. Zou, X. Xu, G.C. Y. Chiou; Evaluation of the Effect of D–Timolol on Rat Experimental Choroidal Neovascularization (CNV) in vivo and Endothelial Cells in vitro . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3024.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Impairment of choroidal perfusion was found in AMD patients. We postulated that vasoactive agents, which can reduce choroidal blood flow resistance, might prevent the development of CNV. D–Timolol is a hypotensive agent used in cardiovascular and glaucoma therapy. Its effect on laser–induced experimental CNV rat model and Human Umbilical Vein Endothelial Cells (HUVEC) were thus evaluated. Methods: (1) Male Brown Norway rats, weighing 150–200g were anesthetized to receive Nd:YAG laser to break the Bruch’s membrane. D–Timolol was given once daily through intraperitoneal injection after laser treatment at 5mg/Kg/d and 15mg/Kg/d for 4 weeks. Fluorescein angiography was performed on week two and week four with a digital fundus camera and standard fluorescein filter. (2) HUVEC from passage 2–7 were tested with proliferation assay and adhesion assay with D–timolol at concentrations of 1–100µg/ml. Results: D–timolol reduced the fluorescein leakage in laser–induced CNV model. The proportion of the prominent leaking lesions was reduced to 81.3% at dose of 15mg/kg/d compared with 96.8% in the control group. D–Timolol can also interfere the endothelial cells proliferation significantly. After incubation with D–Timolol for 48 hours, cells population was reduced to about 75% of the control group. Conclusions: D–Timolol was found to prevent CNV development in laser–induced model in vivo and inhibit vascular endothelial cells proliferation in vitro. It indicates that vasoactive drugs might be a new class of drugs that should be taken into consideration for AMD treatment although further investigation is needed.
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