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Nicotine Increases Size and Severity of Experimental Choroidal Neovascularization

2003; Cadmus Press; Volume: 45; Issue: 1 Linguagem: Inglês

10.1167/iovs.03-0733

1552-5783

Ivan J. Sun er, Diego G. Espinosa‐Heidmann, Maria E. Marin‐Castaño, Eleut P. Hernandez, Simone Pereira‐Simon, Scott W. Cousins,

Angiogenesis and VEGF in Cancer

Cigarette smoking is the strongest environmental risk factor for all forms of age-related macular degeneration (AMD). In the present study, the influence of nicotine on the severity of choroidal neovascularization (CNV) in a mouse model of neovascular AMD and its effects on vascular smooth muscle cells derived from mouse choroid were investigated.A mouse model for CNV was used to study the effects of nicotine in young and middle-aged mice. Nicotine was administered orally in the drinking water to achieve serum levels consistent with those of chronic smokers. Hexamethonium, a nonspecific nicotinic receptor antagonist, was injected subconjunctivally to counteract the effects of nicotine. A mouse choroidal vascular smooth muscle cell line was exposed to nicotine, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), or a combination of one of the factors and nicotine. Cell growth was determined by cell counts, and the activity of matrix metalloproteinase (MMP)-2 and -9 was quantified by gel zymography.Nicotine administration resulted in increased size and vascularity of CNV, and older mice developed a greater relative increase than younger mice. This effect was blocked by subconjunctival hexamethonium. Choroidal vascular smooth muscle cells demonstrated a statistically significant increase in growth after exposure to a combination of PDGF and nicotine. Nicotine also reversed VEGF-induced suppression of MMP-2 activity.Nicotine increases size and severity of experimental CNV in the present mouse model, possibly by potentiating PDGF-mediated upregulation of proliferation of choroidal smooth muscle cells or by other mechanisms. These results suggest that non-neuronal nicotinic receptor activation probably mediates some of the harmful effects of cigarette smoking in wet AMD.