Induction of IL-8, MCP-1, and bFGF by TNF-α in retinal glial cells: implications for retinal neovascularization during post-ischemic inflammation

Laboratory Investigation

DOI: 10.1007/s00417-004-0874-2

Cite this article as:
Yoshida, S., Yoshida, A. & Ishibashi, T. Graefe's Arch Clin Exp Ophthalmol (2004) 242: 409. doi:10.1007/s00417-004-0874-2



We have demonstrated that macrophages/microglia were activated during post-ischemic inflammation in a mouse model of ischemic retinal neovascularization, and that the angiogenesis induced by tumor necrosis factor-α (TNF-α) appeared to be modulated through such angiogenic factors as interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in microvascular endothelial cells. We have extended these studies, and investigated whether TNF-α is localized in macrophages/microglia in the mouse model of retinal neovascularization, and whether TNF-α can induce angiogenic factors in retinal glial cells.


C57BL/6 J pups were placed in a 75% oxygen environment on postnatal day 7 (P7) for 5 days and then returned to room air. The co-localization of TNF-α with macrophages/microglia in the ischemic retina was examined by fluorescent immunohistochemistry. Bovine retinal glial cells were isolated for Northern blot analysis to quantify the expression levels of monocyte chemotactic protein-1 (MCP-1), IL-8, bFGF, and VEGF.


Double staining of retinas revealed that the TNF-α expression level was enhanced in macrophages/microglia 4 days after the hypoxia. Cellular mRNA levels of MCP-1, IL-8, and bFGF, but not VEGF, were increased after treating retinal glial cells with TNF-α (100 U/ml).


The results indicate that TNF-α is produced by activated macrophages/microglia and may participate in retinal neovascularization during post-ischemic inflammation through the induction of potent angiogenic factors in an autocrine or paracrine manner.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Shigeo Yoshida
    • 1
  • Ayako Yoshida
    • 1
  • Tatsuro Ishibashi
    • 1
  1. 1.Department of OphthalmologyKyushu University Graduate School of MedicineFukuokaJapan