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

  • J Mol Med (Berl). 2019 Sep;97(9):1273-1283. doi: 10.1007/s00109-019-01794-w.
Filippo Locri  1  2 ,  Massimo Dal Monte  2 ,  Monica Aronsson  1 ,  Maurizio Cammalleri  2 ,  Mario De Rosa  3 ,  Vincenzo Pavone  4 ,  Anders Kvanta  1 ,  Paola Bagnoli  2 ,  Helder André  5
Affiliations
  • 1. Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Polhemsgatan 50, 112 82, Stockholm, Sweden.
  • 2. Department of Biology, University of Pisa, Pisa, Italy.
  • 3. Department of Experimental Medicine, Second University of Naples, Naples, Italy.
  • 4. Department of Chemical Sciences, University of Naples Federico II, Naples, Italy.
  • 5. Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Polhemsgatan 50, 112 82, Stockholm, Sweden. [email protected].
PMID: 31243519 DOI: 10.1007/s00109-019-01794-w
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.

Keywords
Antiangiogenic drug; Cenupatide; Inflammation; Rubeosis iridis; UPARANT.
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