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M. Yuan, A. Wang, A. Ingerman; Increased Oxidative Stress in "Smoking Mouse" Model of Dry AMD. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6154.
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Smoking is a primary risk factor associated with age-related macular degeneration (AMD). Exposure of mice to cigarette smoke (smoking mice) may be a reliable means of inducing dry AMD-like pathophysiology. The objective of this research is to assess the suitability of this model by characterizing oxidative stress markers in the RPE/choroid of "smoking mice".
At 8 weeks of age, 18 C57BL/6 mice were placed in a smoking chamber for 6 hours/day and 5 days/week for either one or six months. 12 unexposed C57BL/6 mice were used as controls. Levels of lipid oxidative biomarker 4-hydroxynonenal (4-HNE), protein oxidative biomarker nitrotyrosine, oxidative DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHdG), and advanced glycation end products (AGEs) in the RPE/choroid were assessed using immunohistochemistry (IHC) and/or western blot (WB). The localization of these oxidative stress markers, as well as protein stress markers αB crystallin, βS crystallin, and polyubiquitin, was observed by immunofluorescence and confocal microscopy. RPE cell number was counted in sagittal sections of the central retina, including the optic nerve, in both control mice and smoking mice after one month of exposure.
4-HNE, nitrotyrosine, 8-OHdG, αB crystallin, βS crystallin, and polyubiquitin levels were significantly higher in the RPE/choroid of mice exposed to smoke for six months compared to controls. These markers were also found in Bruch’s membrane of smoking mice and not in controls. After one month, 4-HNE, nitrotyrosine and 8-OHdG were found in the RPE of smoking mice but not in controls. 161+/-19 RPE cells per sagittal section were recorded in one-month control mice, and 144+/-13 RPE cells per section were found in one-month smoking mice (n=5, p=0.009).
Mice exposed to cigarette smoke for six months show increased signs of oxidative stress, a factor believed to play a major role in the development of AMD. After only one month of exposure, smoking mice showed higher levels of the oxidative stress marker 4-HNE, 8-OHdG and nitrotyrosine and also exhibited decreased RPE cell counts. These data suggest that the smoking mouse model may be a reliable model for retinal pathophysiology associated with dry AMD.
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