UPARANT is an effective antiangiogenic agent in a mouse model of rubeosis iridis.
Filippo LocriMassimo Dal MonteMonica AronssonMaurizio CammalleriMario De RosaVincenzo PavoneAnders KvantaPaola BagnoliHelder AndréPublished in: Journal of molecular medicine (Berlin, Germany) (2019)
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.
Keyphrases
- vascular endothelial growth factor
- extracellular matrix
- endothelial cells
- inflammatory response
- high glucose
- mouse model
- oxidative stress
- randomized controlled trial
- systematic review
- anti inflammatory
- end stage renal disease
- skeletal muscle
- adipose tissue
- diabetic retinopathy
- prognostic factors
- combination therapy
- electronic health record
- high fat diet induced
- long non coding rna
- chronic kidney disease
- lps induced
- ultrasound guided
- optical coherence tomography
- wild type