Abstract
Abstract: :
Purpose:Cigarette smoking has been associated with an increased risk of age-related macular degeneration (ARMD) and choroidal neovascularization (CNV). Nicotine, a major toxic component of cigarette smoke, is a potent injury stimulus for vascular endothelium and can induce vascular endothelial proliferation. We sought to determine the effects of nicotine exposure in a mouse model of CNV, and whether age-dependent differences in susceptibility were present. Methods: A laser model for CNV was used to study the effects in young (4 mos) and aged (11 mos) C57BL/6 mice. Nicotine was administered in drinking water (100 ug/ml) in experimental animals two days prior to laser exposure and continued for two or four weeks after laser injury. Experimental and control animals were then injected with fluoresceinated dextran, then the right eyes were removed and prepared for flat-mount analysis of CNV surface area (in relative disc areas). The mice were perfused and fixed with glutaraldehyde and formalin. The left eyes were removed for histopathology. Results: Older mice exposed to nicotine had larger CNV than control mice (1.80.2 DA vs 1.00.1 DA). Cellularity and vascularity also increased in nicotine-exposed older mice. In contrast, young mice were less susceptible to the effects of nicotine (1.2±0.1 DA in treated eyes v 1.0±0.1 DA in controls). Cellularity and vascularity were not significantly different. Conclusion: In mice, exposure to nicotine results in increased size of CNV, but the effect is more pronounced in older mice. Ongoing studies are designed to understand the mechanisms for the age-dependent toxic effects of cigarette smoke.
Keywords: 308 age-related macular degeneration • 346 choroid: neovascularization • 316 animal model