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Lily L Wong, Swetha Barkam, Sudipta Seal; Distinct Cellular Uptake and Clearance Patterns of Nanoceria in the Retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1205.
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© ARVO (1962-2015); The Authors (2016-present)
Our stable water-dispersed, catalytic nanoceria have anti-oxidative effects in rodent models of retinal degeneration. A single intravitreal injection of nanoceria delays disease progression from weeks to months. Even though we have shown that our synthesized nanoceria are rapidly taken up by retinal cells, retained in the retina for over a year, and are non-toxic, we still do not know which cell types in the retina preferentially take up these nanoparticles. In this study, we examined the temporal and spatial distribution of fluorescently-labeled nanoceria in retinal sections to better understand the cellular action of nanoceria.
We compared the in situ distribution of the fluorescent dye, Alexa647 NHS ester (Al647), and Alexa647-conjugated nanoceria (Al647-CeNPs) in retinal sections at various time points post intravitreal injection. We delivered 1 µl of either Al647 or Al647-CeNPs to the vitreous of Balb C mice. We detected the dim fluorescent signals using the ultra-high sensitivity detector equipped in our Olympus FV1200 confocal system. Quantitative intensity analyses were performed using the Fluoview software.
We detected minute autofluorescence in the neurofiber layer (NFL), inner plexiform layer (IPL), outer plexiform layer (OPL), and rod inner and outer segments (IS/OS) of uninjected Balb C mice. In Al647 injected mice, we detected robust signals in vascular cells in the intra-retinal vasculature and detectable signals in the NFL and IPL from 1 day to 2 months post injection (pi) with decreasing intensity over time. In Al647-CeNPs injected ones, we failed to detect signals in 7 dpi but detected the highest signal level at 14 dpi with decreasing signal intensity from 1 to 3 months pi. We observed signals in the NFL, IPL, OPL, IS/OS, apical region of retinal pigment epithelium (RPE), with the highest signals found in photoreceptor (Pr) OS. Unlike Al647 injected animals, we did not observe enhanced signals in retinal vascular cells.
We conclude that nanoceria follow distinct uptake and clearance pathways from other small molecules after delivery to the vitreous. They are taken up by the six major neuronal cell types and Muller Glia, and accumulate in the OS of Pr cells. They are likely to be eliminated by RPE through the shedding of Pr OS. Consistent with prior retention studies, we observe fluorescent signals in retinal cells months after a single intravitreal injection.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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