Retinal angiogenesis suppression through small molecule activation of p53 Academic Article uri icon


MeSH Major

  • Angiogenesis Inhibitors
  • Imidazoles
  • Neovascularization, Physiologic
  • Piperazines
  • Retinal Vessels
  • Tumor Suppressor Protein p53


  • Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokine-targeted antiangiogenesis therapies.

publication date

  • October 2013



  • Academic Article



  • eng

PubMed Central ID

  • PMC3784529

Digital Object Identifier (DOI)

  • 10.1172/JCI67315

PubMed ID

  • 24018558

Additional Document Info

start page

  • 4170

end page

  • 81


  • 123


  • 10