Retinal angiogenesis suppression through small molecule activation of p53 (Articolo in rivista)

Type
Label
  • Retinal angiogenesis suppression through small molecule activation of p53 (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1172/JCI67315 (literal)
Alternative label
  • Chavala SH, Kim Y, Tudisco L, Cicatiello V, Milde T, Kerur N, Claros N, Yanni S, Guaiquil VH, Hauswirth WW, Penn JS, Rafii S, De Falco S, Lee TC, Ambati J. (2013)
    Retinal angiogenesis suppression through small molecule activation of p53
    in The Journal of clinical investigation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Chavala SH, Kim Y, Tudisco L, Cicatiello V, Milde T, Kerur N, Claros N, Yanni S, Guaiquil VH, Hauswirth WW, Penn JS, Rafii S, De Falco S, Lee TC, Ambati J. (literal)
Pagina inizio
  • 4170 (literal)
Pagina fine
  • 4181 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 123 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 10 (literal)
Note
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Ophthalmology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA. Department of Ophthalmology and Visual Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA. Angiogenesis Lab, Institute of Genetics and Biophysics - CNR, Napoli, Italy. Howard Hughes Medical Institute, Ansary Center for Stem Cell Therapeutics, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York, USA. Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, Germany. Vanderbilt Eye Institute, Vanderbilt University, Nashville, Tennessee, USA. Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York, USA. Powell Gene Therapy Center, Departments of Ophthalmology and Pediatrics, University of Florida, Gainesville, Florida, USA. Retina Institute, Vision Center, Childrens Hospital Los Angeles, Los Angeles, California, USA. (literal)
Titolo
  • Retinal angiogenesis suppression through small molecule activation of p53 (literal)
Abstract
  • 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. (literal)
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