Detection of inducible nitric oxide synthase and vascular endothelial growth factor in choroidal neovascular membranes

Ophthalmologica. 2002 May-Jun;216(3):209-14. doi: 10.1159/000059634.


Vascular endothelial growth factor (VEGF) is among the cytokines which have been implicated in the pathogenesis of choroidal neovascularization secondary to age-related macular degeneration (ARMD). There is, however, evidence that intercellular signaling molecules, such as nitric oxide (NO), are involved in this process. NO is synthesized via the inducible isoform of NO synthase (iNOS), which is expressed after induction by cytokines. In the current study, we investigated whether VEGF and iNOS are coexpressed in choroidal neovascular membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and in spatial relation to vessel walls. As scored by light microscopy, we found a significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341) in vascular endothelial cells. Our study supports a significant role for iNOS in the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our findings suggest a possible relationship between NO and VEGF in the regulation of pathologic angiogenesis in this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / metabolism*
  • Cytokines
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymphokines / metabolism*
  • Macrophages / enzymology
  • Macular Degeneration / complications*
  • Nitric Oxide
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Pigment Epithelium of Eye / enzymology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Cytokines
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II