May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Nicotine Intensifies Choroidal Plasminogenesis and Matrix Destruction
Author Affiliations & Notes
  • S. Shen
    Pathology, U-Conn Health Center, Farmington, CT, United States
  • X. Jiang
    Pathology, U-Conn Health Center, Farmington, CT, United States
  • X. Li
    Pathology, U-Conn Health Center, Farmington, CT, United States
  • R.E. Cone
    Pathology, U-Conn Health Center, Farmington, CT, United States
  • J. O'Rourke
    Pathology, U-Conn Health Center, Farmington, CT, United States
  • Footnotes
    Commercial Relationships  S. Shen, None; X. Jiang, None; X. Li, None; R.E. Cone, None; J. O'Rourke, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1618. doi:
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      S. Shen, X. Jiang, X. Li, R.E. Cone, J. O'Rourke; Nicotine Intensifies Choroidal Plasminogenesis and Matrix Destruction . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1618.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Smoking is a risk factor for macular degeneration. But a mechanism for this association has not been established. Nicotine stimulates a strong sympathetic discharge. The dense sympathetic innervation of the uvea releases high levels of enzymatically active tissue plasmingen activator(t-PA) that is synthesized by superior cervical ganglion neurons. An excessive t-PA release stimulated by nicotine would increase the local plasmin production. Plasmin aggressively degrades Bruch’s membrane proteins and is a principal activator of latent metalloproteinases. This study examined whether nicotine stimulates an increased release of active t-PA from the choroid and anterior uvea. Methods: We measured the t-PA release from choroids isolated in superfused rat eyecups. These were compared to densely and sparsely innervated artery segments. The nicotine bitartrate dose was 10-7M. The in vivo t-PA release from anterior uveal axons into aqueous humor was assayed following intravenous 10µg nicotine infusions. T-PA immunolocalizations in uveal sympathetic axons were confirmed by electron and light microscopy. Results: The isolated choroid basal t-PA release nearly doubled following nicotine infusion(0.184±0.02 to 0.35±0.05IU/mg:p<0.01,n=9).Mesenteric artery segment basal release per mg was half that of the choroid and rose only 26% following nicotine stimulation. Sparsely innervated carotid segment basal and nicotine-induced t-PA releases were negligible. Intravenous nicotine nearly tripled the basal aqueous humor t-PA activity(0.38±0.1 to 1.07±0.08IU/ml),while plasma levels rose only 20%(0.87±0.04 to 1.04±0.04 IU/ml: p<0.01,n=4). Conclusions: (1) Nicotine strongly enhances t-PA release from the choroid and anterior uvea, consistent with its dense innervation by t-PA-bearing sympathetic nerve fibers. (2) These findings are compatible with an enhanced plasmin proteolysis and metalloproteinase degradation of the macular matrix during chronic nicotine use. (3) Intensified plasminogenesis is a recognized pathogenic mechanism for matrix proteolysis that could explain the association of chronic smoking with macular degeneration.

Keywords: choroid • macula/fovea • proteolysis 
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