Retinal Neovascularization Is Altered in TNF-Receptor Deficient Mice in Oxygen-Induced Retinopathy

Abstract

Abstract: : Purpose: Tumor necrosis factor alpha is one of the major cytokines in inflammation and apoptosis. Previous studies have demonstrated that inhibition of TNF alpha can reduce leukocyte adhesion and vascular leakage (Joussen et al. 2002), but also apoptotic endothelial cell death in diabetes. Here we investigate the effect of TNF-Rp55 and TNF-Rp75 on the retinal development in oxygen-induced retinopathy. Methods: TNF-Rp55 and TNF-Rp75 deficient mice backcrossed to C57/Bl6 mice as well as their respective wildtype controls were exposed to 70% oxygen from postnatal day 7 to day 12. Retinal vascularization was investigated in flat mount preparations after lectin labeling of endothelial cells on day 14, 17 and day 20. Retinal mRNA Expression of VEGF and Angiopoietins was examined at corresponding time points. Results: TNF-Rp55 and TNF-Rp75 deficient mice demonstrated similar retinal development and vascularization. In comparison to wildtype mice, the vascularized area was not altered at any of the observation time points. Treatment with oxygen resulted in a tendentious earlier vascularization in TNF-Rp75 deficient mice. All groups demonstrated a significant enlargement of retinal vessels with formation of neovascularisation early after oxygen treatment. After oxygenation in TNF-Rp55 deficient mice angiopoietin-1 and angiopoietin-2 was significantly reduced compared to controls. Conclusions: The current study demonstrates that inhibition of TNF alpha via both TNF-Rp55 and TNF-Rp75 can alter retinal development and angiogenesis in a model of oxygen-induced retinopathy. These data underscore the potential utility of anti-inflammatory treatment in oxygen-induced retinopathy.

Keywords: retinal neovascularization • transgenics/knock-outs • animal model