Nicotine Increases Size and Severity of Experimental Choroidal Neovascularization

• Published in: Investigative ophthalmology & visual science Vol. 45; no. 1; pp. 311 - 317
• Main Authors: Suner, Ivan J, Espinosa-Heidmann, Diego G, Marin-Castano, Maria E, Hernandez, Eleut P, Pereira-Simon, Simone, Cousins, Scott W
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.01.2004; Association for Research in Vision and Ophtalmology
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Cell Division - drug effects; Choroid - blood supply; Choroid - drug effects; Choroidal Neovascularization - metabolism; Choroidal Neovascularization - pathology; Disease Models, Animal; Drug Combinations; Female; Fluorescein Angiography; Hexamethonium - pharmacology; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Nicotinic Antagonists - pharmacology; Platelet-Derived Growth Factor - pharmacology; Tobacco, tobacco smoking; Toxicology; Vascular Endothelial Growth Factor A - pharmacology; Human; Eye; Eye disease; Choroidal neovascularization; Toxicity; Size; Tobacco smoking; Increase; Nicotine
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.03-0733

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.