Size-Dependent Cytotoxicity and Reactive Oxygen Species of Cerium Oxide Nanoparticles in Human Retinal Pigment Epithelia Cells

Abstract

Purpose: The use of cerium oxide nanoparticles (CeO 2 NPs), a lanthanide element oxide and bivalent compound, has been growing continuously in industry and biomedicine. Due to their wide application, the potential human health problems of CeO 2 NPs have attracted attention, but studies on the toxicity of this compound to human eyes are lacking. This study investigated the cytotoxicity and reactive oxygen species (ROS) of CeO 2 NPs in human retinal pigment epithelial cells (ARPE-19 cells). Methods: Using the transmission electron microscope (TEM), the size distribution and shape of CeO 2 NPs were characterized. To explore the effect of CeO 2 NP size on ophthalmic toxicity in vitro, three sizes (15, 30 and 45 nm) of CeO 2 NPs were investigated using ATP content measurement, LDH release measurement and cell proliferation assay in ARPE-19 cells. ROS values and mitochondrial membrane potential depolarization were evaluated by H 2 DCF-DA staining and JC-1 staining. Morphology changes were detected using a phase-contrast microscope. Results: The cytotoxicity of 15 nm CeO 2 NPs was found to be the highest and hence was further explored. Treatment with 15 nm CeO 2 NPs caused the morphology of ARPE-19 cells to change in a dose- and time-dependent manner. Moreover, the treatment induced excessive ROS generation and mitochondrial membrane potential depolarization. In addition, cytotoxicity was attenuated by the application of a ROS scavenger N-acetyl-L- cysteine (NAC). Conclusion: CeO 2 NPs induced cytotoxicity in ARPE-19 cells and excessive production of ROS and decreasing mitochondrial membrane potential. The Overproduction of ROS partially contributes to CeO 2 NP-induced cytotoxicity. Keywords: nanomaterials, ophthalmic toxicity, oxidative stress, mitochondrial membrane potential depolarization

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