Transcription of Inflammatory Cytokine TNFα is Upregulated in Retinal Angiogenesis under Hyperoxia

Cell Physiol Biochem. 2016;39(2):573-83. doi: 10.1159/000445649. Epub 2016 Jul 11.

Abstract

Background/aims: Hypoxia induces angiogenesis while hyperoxia promotes vasoregression in the retina. We investigated herein the effect of prolonged hyperoxia on retinal angiogenesis and the underlying mechanism in an oxygen-induced retinopathy (OIR) model.

Methods: Vascular morphology was quantified in whole-mount retina from the mice subjected to the conventional OIR model (c-OIR) or the OIR model with prolonged hyperoxia (p-OIR). Expressions of genes related to angiogenesis were determined by real-time PCR.

Results: p-OIR retinas showed few intraretinal neovascular tufts at the border of avascular zones, lacking preretinal neovascularization, whereas c-OIR retinas had numerous preretinal neovascularizations. p-OIR retinas demonstrated outgrowth of capillaries in the deep layers despite persistent hyperoxia and possess a larger avascular zone compared with the c-OIR retinas. The capillaries in the p-OIR retinas were well-formed in contrast to those in the c-OIR retinas. p-OIR retinas expressed significantly higher TNFα (∼4 fold) than c-OIR retinas. The expression of vascular endothelial growth factor, Erythropoietin, Angiopoietin 1 and 2 remained unchanged.

Conclusion: Our data demonstrate that TNFα transcription is increased in hyperoxia-promoted retinal angiogenesis, implicating it, in association with low VEGF levels, as a possible proponent in retinal angiogenesis under hyperoxia.

MeSH terms

  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism
  • Angiopoietin-2 / genetics
  • Angiopoietin-2 / metabolism
  • Animals
  • Erythropoietin / genetics
  • Erythropoietin / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Hyperoxia*
  • Hypoxia
  • Mice, Inbred C57BL
  • Retinal Neovascularization / genetics*
  • Retinal Neovascularization / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiopoietin-1
  • Angiopoietin-2
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Erythropoietin