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UPARANT is an effective antiangiogenic agent in a mouse model of rubeosis iridis.

Abstract
Puncture-induced iris neovascularization (rubeosis iridis; RI) in mice is associated with upregulation of extracellular matrix (ECM) degradation and inflammatory factors. The anti-angiogenic and anti-inflammatory efficacy of UPARANT in reducing RI was determined by noninvasive, in vivo iris vascular densitometry, and confirmed in vitro by quantitative vascular-specific immunostaining. Intravitreal administration of UPARANT successfully and rapidly reduced RI to non-induced control levels. Molecular analysis revealed that UPARANT inhibits formyl peptide receptors through a predominantly anti-inflammatory response, accompanied with a significant reduction in ECM degradation and inflammation markers. Similar results were observed with UPARANT administered systemically by subcutaneous injection. These data suggest that the tetrapeptide UPARANT is an effective anti-angiogenic agent for the treatment of RI, both by local and systemic administrations. The effectiveness of UPARANT in reducing RI in a model independent of the canonical vascular endothelial growth factor (VEGF) proposes an alternative for patients that do not respond to anti-VEGF treatments, which could improve treatment in proliferative ocular diseases. KEY MESSAGES: UPARANT is effective in the treatment of rubeosis iridis, both by local and systemic administrations. UPARANT can reduce VEGF-independent neovascularization.
AuthorsFilippo Locri, Massimo Dal Monte, Monica Aronsson, Maurizio Cammalleri, Mario De Rosa, Vincenzo Pavone, Anders Kvanta, Paola Bagnoli, Helder André
JournalJournal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 97 Issue 9 Pg. 1273-1283 (09 2019) ISSN: 1432-1440 [Electronic] Germany
PMID31243519 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Biomarkers
  • Vascular Endothelial Growth Factor A
Topics
  • Angiogenesis Inhibitors (pharmacology)
  • Animals
  • Biomarkers (metabolism)
  • Disease Models, Animal
  • Female
  • Inflammation (drug therapy, metabolism)
  • Iris (drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic (drug therapy, metabolism)
  • Vascular Endothelial Growth Factor A (metabolism)

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