Purchase this article with an account.
I.J. Suner, D.G. Espinosa–Heidmann, S.W. Cousins; Cigarette Smoke and Nicotine Both Increase Recruitment of Activated Macrophages in Early Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1531. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The mechanism for smoking– and nicotine–mediated increased severity in exudative AMD is unknown. In this project, we propose the hypothesis that cigarette smoke and nictotine promote activation of macrophages, which, in turn, leads to more severe CNV. We performed a preliminary experiment to test this idea.
A laser–induced CNV mouse model was used. Three groups were studied: cigarette smoke, nicotine, and control (n=5 per group). At day three post laser (the critical period for macrophage contribution to this model), eyes were recovered for immunohistochemistry. They were double stained for F4/80+ macrophages (red) and one of two activation markers (green): TNF–α or COX–2.
As shown in the Figure (merged image, yellow = TNF–α + macrophages), as compared to controls, both nicotine– and smoke–exposed mice demonstrated CNV with greater frequency of macrophages and more importantly, greater frequency of TNF–α expressing macrophages (yellow) (41±3% in control mice vs 70±2% of activated macrophages in smoke–exposed mice, P<0.01). Staining for COX–2 revealed similar findings (not shown). Importantly, F4/80+ cells in the choroid distant from CNV (i.e., so called tissue–resident macrophages) were not positive for TNF– α, suggesting that only recruited blood–derived macrophages, and not resident macrophages, were affected by smoke.
Cigarette smoke– and nicotine–exposed mice both demonstrated preferential recruitment of activated macrophages into CNV early in lesion development, suggesting that macrophage activation may be an important mechanism for the association of cigarette smoking and AMD.
This PDF is available to Subscribers Only