Nicotine Increases Size and Severity of Experimental Choroidal Neovascularization

Ivan J. Suñer, Diego G. Espinosa-Heidmann, Maria E. Marin-Castano, Eleut P. Hernandez, Simone Pereira-Simon, Scott W. Cousins

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

PURPOSE. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)311-317
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2004

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Suñer, I. J., Espinosa-Heidmann, D. G., Marin-Castano, M. E., Hernandez, E. P., Pereira-Simon, S., & Cousins, S. W. (2004). Nicotine Increases Size and Severity of Experimental Choroidal Neovascularization. Investigative Ophthalmology and Visual Science, 45(1), 311-317. https://doi.org/10.1167/iovs.03-0733