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Xue Cai, Sudipta Seal, James F McGinnis; Nanoceria are not toxic at maximum dosage in murine retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1678.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that cerium oxide nanoparticles (nanoceria) catalytically scavenge Reactive Oxygen Species (ROS) and can long-term inhibit retinal degeneration in tubby mice and inhibit/regress neovascularization in vldlr-/- mice. However, the toxicity of nanoceria retention in the retina was unknown. The current study is proposed to address this point.
Wild type (C57BL/6J) mice at P30 were intravitreally injected with increasing doses of nanoceria (0.1mM, 0.3mM, 1mM, 3mM and 10mM) in 1µl saline. Saline injection and uninjected mice served as controls. Retinal structure, ONL (outer nuclear layer) thickness and cellular infiltration were analyzed using H & E stained slides at post injection (PI) 7h, 3d, 7d, 15d and 30d. Retinal function was evaluated with electroretinography at PI 30d. The fundus abnormality and angiogenesis were assessed with fundoscopy and fluorescence angiography. The expression of inflammatory cytokines and markers of activation of microglia/macrophages were analyzed by qRT-PCR or western blots at PI 7h.
Intravitreal injection of all concentrations of nanoceria did not cause changes in retinal morphology and ONL thickness compared to untreated and saline injected groups indicating that no photoreceptor death was induced. No cellular infiltration was seen in the histological slides. Decrease of retinal function was not found. There is no elevation in the expression of TNFα, IL-1β, MIF and GFAP.
High concentrations of nanoceria do not cause any damage to retinal structure and function. No cellular infiltration and no increases in inflammation responses were found in the eyes. Our data indicate that nanoceria are safe to use for treatment of a variety of eye diseases.
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