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Fredrik Johansson, Patrik Bauer, Birgitta Sandström, Erika Söderstjerna, Ulrica Englund Johansson; Effects of Silver- and Gold Nanoparticles on the Retina - In Vitro and In Vivo. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4898.
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© ARVO (1962-2015); The Authors (2016-present)
The goal is to explore the potential use of nanoparticles (NPs) as carriers in drug delivery of therapeutical agents to the retina. Nanomaterials are increasingly used in diagnostics, imaging and targeted drug delivery. In the clinic, Au-NPs are employed as e.g. anti-cancer agents and Ag-NPs are commonly used due to their antibacterial effects. Despite widespread use, the documentation is limited on the direct effect of Ag- and Au-NPs on eukaryotic cells, including human cells and the eye/retina. Here we investigate the uptake and distribution of especially Ag- and Au-NPs, as well as their possible toxic effect in a battery of assays ranging from human neural cells to the mouse eye in vivo.
Low concentrations of Ag- and Au-NPs are studied at a cellular-, tissue and organ level, using a human neural stem cell line, organotypic cultures of the mouse retina and administration the mouse eye in vivo. Uptake of the NPs is analyzed using TEM. Using the human cells effects on viability (MTT and TUNEL assays), cell proliferation (Ki67 marker), cell cycle analysis and phenotypic differentiation (GFAP (glial/neural) and DCX (neuronal) markers) were studied. In retinal models adverse effects were studied using the parameters: gross morphology, glial- and microglial response, cytotoxic effects (apoptosis (TUNEL assay) and oxidative stress (AvidinD staining)). Ag- and Au-NPs of two different sizes are included, 20 and 80 nm, respectively.
We demonstrate that 20 and 80 nm Ag- and Au-NPs are taken up into the cytoplasm, nucleus and mitochondria in the retina in vitro, using TEM analysis. Adverse effects noted on the retina with changes in gross morphology and elevated glial- and microglial response. Moreover, neuronal toxicity (apoptosis and oxidative stress) was primarily seen in the outer nuclear layer, harboring the photoreceptors. In corresponding in vivo experiments preliminary results show no significant oxidative stress. Analysis is on-going revealing if the in vitro data can be extrapolated to the in vivo situation. Noteworthy, significant adverse effects on cell growth profile and morphology is documented and studies on the eventual effects on phenotypic differentiation are on-going.
In summary, our results strongly suggests that careful investigation is needed on the eventual adverse effects of Ag- and AuNPs if these are considered for usage in both daily consumer products and medicine.
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