Abstract
The complex network of neuronal cells in the retina makes it a potential target of neuronal toxicity – a risk factor for visual loss. With growing use of nanoparticles (NPs) in commercial and medical applications, including ophthalmology, there is a need for reliable models for early prediction of NP toxicity in the eye and retina. Metal NPs, such as gold and silver, gain much of attention in the ophthalmology community due to their potential to cross the barriers of the eye. Here, NP uptake and signs of toxicity were investigated after exposure to 20 and 80 nm Ag- and AuNPs, using an in vitro tissue culture model of the mouse retina. The model offers long-term preservation of retinal cell types, numbers and morphology and is a controlled system for delivery of NPs, using serum-free defined culture medium. AgNO3-treatment was used as control for toxicity caused by silver ions. These end-points were studied; gross morphological organization, glial activity, microglial activity, level of apoptosis and oxidative stress, which are all well described as signs of insult to neural tissue. TEM analysis demonstrated cellular- and nuclear uptake of all NP types in all neuronal layers of the retina. Htx-eosin staining showed morphological disruption of the normal complex layered retinal structure, vacuole formation and pyknotic cells after exposure to all Ag- and AuNPs. Significantly higher numbers of apoptotic cells as well as an increased number of oxidative stressed cells demonstrated NP-related neuronal toxicity. NPs also caused increased glial staining and microglial cell activation, typical hallmarks of neural tissue insult. This study demonstrates that low concentrations of 20 and 80 nm sized Ag- and AuNPs have adverse effects on the retina, using an organotypic retina culture model. Our results motivate careful assessment of candidate NP, metallic or-non-metallic, to be used in neural systems for therapeutic approaches.
Highlights
Retinal dysfunction caused by disease, damage or external factors often lead to visual loss
The diameters of the four different NPs were measured from transmission electron microscopy (TEM) images (Figs. 1A, 2A–D) and were closely similar to the values 20 and 80 nm, provided by BBI, UK. The larger particles, both Au and Ag, were found to contain a portion of non-spherical particles (Figs. 2B and D). These non-spherical particles were included in the size measurements and influenced the standard deviations, which were found to be larger than for the smaller particles
The particle size was determined in suspension by Dynamic Light Scattering (DLS) and by Differential Centrifugal Sedimentation (DCS), Figure 1A
Summary
Retinal dysfunction caused by disease, damage or external factors often lead to visual loss. Up-to-date several nano-sized materials have been applied in ocular research, spanning from metals, carbon, polymers and silica to materials of biological origin, such as lipids or lactic acid [7]. Both for commercial and clinical use, Au- and AgNPs, have been intensively studied, AuNPs due to their good intrinsic properties, i.e. high chemical stability, well-controlled size and surface functionalization, and AgNPs due to their antibacterial effect, often applied in wound disinfection, coatings of medical devices and prosthesis, and commercially in textiles, cosmetics and household goods [9]
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