Antioxidant Properties of Cerium Oxide Nanoparticles Prevent Retinal Neovascular Alterations In Vitro and In Vivo

In this study, we investigated whether cerium oxide nanoparticles (CeO(2)-NPs), a promising antioxidant nanomaterial, may contrast retinal vascular alterations induced by oxidative damage in vitro and in vivo. For the in vivo experiments, the light damage (LD) animal model of Age-Related Macular Degeneration (AMD) was used and the CeO(2)-NPs were intravitreally injected. CeO(2)-NPs significantly decreased vascular endothelial growth factor (VEGF) protein levels, reduced neovascularization in the deep retinal plexus, and inhibited choroidal sprouting into the photoreceptor layer. The in vitro experiments were performed on human retinal pigment epithelial (ARPE-19) cells challenged with H(2)O(2); we demonstrated that CeO(2)-NPs reverted H(2)O(2)-induced oxidative stress-dependent effects on this cell model. We further investigated the RPE–endothelial cells interaction under oxidative stress conditions in the presence or absence of CeO(2)-NPs through two experimental paradigms: (i) treatment of human umbilical vein endothelial cells (HUVECs) with conditioned media from ARPE-19 cells, and (ii) coculture of ARPE-19 and HUVECs. In both experimental conditions, CeO(2)-NPs were able to revert the detrimental effect of H(2)O(2) on angiogenesis in vitro by realigning the level of tubule formation to that of the control. Altogether, our results indicate, for the first time, that CeO(2)-NPs can counteract retinal neovascularization and may be a new therapeutic strategy for the treatment of wet AMD.