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.
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Authors | Filippo Locri, Massimo Dal Monte, Monica Aronsson, Maurizio Cammalleri, Mario De Rosa, Vincenzo Pavone, Anders Kvanta, Paola Bagnoli, Helder André |
Journal | Journal of molecular medicine (Berlin, Germany)
(J Mol Med (Berl))
Vol. 97
Issue 9
Pg. 1273-1283
(09 2019)
ISSN: 1432-1440 [Electronic] Germany |
PMID | 31243519
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Biomarkers
- Vascular Endothelial Growth Factor A
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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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