Insulin-like growth factor-1 contributes to neovascularization in age-related macular degeneration

Biochem Biophys Res Commun. 2004 Oct 29;323(4):1203-8. doi: 10.1016/j.bbrc.2004.08.219.


Choroidal neovascularization (CNV) is a debilitating complication of age-related macular degeneration and a leading cause of vision loss. Along with other angiogenic factors like vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-1 and its receptor, IGF-1R, have been implicated in CNV. IGF-1 is produced in neurons and retinal pigment epithelium (RPE) but its targets and impact in CNV are not understood. IGF-1 immunoreactivity was abundant throughout surgically isolated human CNV tissues and RPE cells were immunopositive for IGF-1R. Cultured RPE cells obtained from CNV tissues expressed IGF-1R. IGF-1 stimulation of cultured cells from CNV tissues induced monophasic sustained rises in intracellular free Ca(2+). VEGF concentration in the medium of unstimulated RPE cell cultures from CNV tissues increased with time to a steady-state (8h) which was increased twofold by IGF-1 stimulation. Thus, in RPE cells IGF-1 stimulates the second messenger Ca(2+) and increases VEGF secretion which, in turn, induces neovascularization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Calcium / metabolism*
  • Cells, Cultured
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / metabolism*
  • Culture Techniques
  • Female
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Macular Degeneration / complications
  • Macular Degeneration / metabolism*
  • Male
  • Middle Aged
  • Pigment Epithelium of Eye / metabolism*
  • Pigment Epithelium of Eye / pathology*
  • Tissue Distribution
  • Vascular Endothelial Growth Factor A / metabolism*


  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor I
  • Calcium