Repeated Topical Administration of 3 nm Cerium Oxide Nanoparticles Reverts Disease Atrophic Phenotype and Arrests Neovascular Degeneration in AMD Mouse Models

Abstract

Increased oxidative stress in the retina and retinal pigment epithelium is implicated in age-related macular degeneration (AMD). Antioxidant cerium oxide nanoparticles (CeO 2 NPs) have been used to treat degenerative retinal pathologies in animal models, although their delivery route is not ideal for chronic patient treatment. In this work, we prepared a formulation for ocular topical delivery that contains small (3 nm), nonaggregated biocompatible CeO 2 NPs. In vitro results indicate the biocompatible and protective character of the CeO 2 NPs, reducing oxidative stress in ARPE19 cells and inhibiting neovascularization related to pathological angiogenesis in both HUVEC and in in vitro models of neovascular growth. In the in vivo experiments, we observed the capacity of CeO 2 NPs to reach the retina after topical delivery and a subsequent reversion of the altered retinal transcriptome of the retinal degenerative mouse model DKO rd8 toward that of healthy control mice, together with signs of decreased inflammation and arrest of degeneration. Furthermore, CeO 2 NP eye drops’ treatment reduced laser-induced choroidal neovascular lesions in mice by lowering VEGF and increasing PEDF levels. These results indicate that CeO 2 NP eye drops are a beneficial antioxidant and neuroprotective treatment for both dry and wet forms of AMD disease.