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Helder Andre, Filippo Locri, Monica Aronsson, Maurizio Cammalleri, Massimo Dal Monte, Paola Bagnoli, Mario De Rosa, Vincenzo Pavone, Anders P Kvanta; UPARANT is an effective antiangiogenic in a novel mouse model of rubeosis iridis associated with neovascular glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1251.
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© ARVO (1962-2015); The Authors (2016-present)
Puncture-induced iris wound healing in mice is associated with upregulation of inflammatory factors and iris neovascularization (rubeosis iridis; NVI). Here, we investigate the anti-angiogenic and anti-inflammatory effectiveness of UPARANT in a new model of rubeosis iridis associated with neovascular glaucoma (NVG).
BALB/c mouse pups of either sex were subjected to uveal puncture to stimulate NVI or injected with ARPE-19 hypoxia-conditioned media to mimic NVG. UPARANT effectiveness in reducing NVI and NVG was determined by noninvasive in vivo iris vascular densitometry, and confirmed in vitro by quantitative vascular-specific CD31 immunostaining. Angiogenic and inflammatory related factors were assayed by quantitative PCR at the transcript level and by semi-quantitative western blot at the protein level.
Our data comparatively analyses antiangiogenic effects UPARANT to a mouse equivalent of aflibercept (VEGFR1 Fc chimera). Intravitreal administration of UPARANT successfully and rapidly reduced iris vasculature to control (non-induced) level, in both NVI and NVG models, while VEGFR1 Fc chimera displays a slower antiangiogenic effect that is not reduced to control levels. Molecular analysis revealed that UPARANT antagonizes formyl peptide receptors (FPR) through a predominantly anti-inflammatory response, accompanied with significant reduction of IL1β, IL6, CXCR4, CCL2, MMP2, MMP9, PAI-1, and uPAR. Furthermore, similar results were observed when UPARANT was administered systemically by subcutaneous injection.
The multitarget peptide UPARANT is superior to anti-VEGF in the treatment of NVI and rubeosis iridis associated with NVG in this novel mouse model. In addition, UPARANT displayed systemic effectiveness in reducing both NVI and NVG, which could provide improved therapy and compliance for proliferative ocular diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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