Sequential induction of angiogenic growth factors by TNF-α in choroidal endothelial cells

Inflammatory mediators have been proposed to play a critical role in the pathogenesis of choroidal neovascularization, a blinding complication of age-related macular degeneration. We evaluated the expression of TNF-alpha in human choroidal neovascular membranes and found that it colocalized with cells expressing VEGF, angiopoictin (Ang)-l and Ang2. In cultured choroidal endothelial cells we found that TNF-alpha increased Ang2 mRNA (increased transcription) and protein levels prior to those of Ang] and VEGF. The results raise the possibility that during neovascularization, TNF-alpha may modulate endothelial plasticity and survival by sequential inactivation of Tie2 followed by activation of Tie2 and VEGF receptors. (c) 2005 Elsevier B.V. All rights reserved.