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 messagesUPARANT is effective in the treatment of rubeosis iridis, both by local and systemic administrations.UPARANT can reduce VEGF-independent neovascularization.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Naples, Italy 4 Department of Chemical Sciences, University of Naples Federico II, Naples, ItalyIn the eye, the vasculature plays a key role in detecting light and supplying oxygen and nutrients
Immunofluorescence assays with cluster of differentiation (CD)31 as an endothelial marker were performed on irises on day 15 (Fig. 2c), and the microvascular bed was analyzed for total vasculature, sprouts, and vascular branching using a vasculature-specific software [20]
The tetrapeptide UPARANT is shown to be effective in mitigating rubeosis iridis (RI), both by intravitreal and subcutaneous administrations, which presents the first evidence of pharmacological treatment in the small rodent model of RI
Summary
Vascular networks and blood vessel numbers are precisely established from development to adulthood, ranging from the avascular cornea and lens for transparency, the fractal retinal vasculature for light sensing, to the highly vascularized uvea for oxygen supply. Iris vasculature originates from the outer uveal limbal limits and is characterized by numerous anastomoses between arteries and veins. This peculiar vascular architecture allows iris blood vessels to supply oxygen and nutrients to the anterior segment and maintain corneal and lens homeostasis [1]. Angiogenesis, the formation of new blood vessels from the existing vascular bed, is fundamental in various physiological processes, including development and wound healing. Angiogenesis is finely regulated by various factors, such as vascular
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