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Silver and gold nanoparticles exposure to in vitro cultured retina - studies on nanoparticle internalization, apoptosis, oxidative stress, glial- and microglial activity.

Söderstjerna, Erika LU ; Bauer, Patrik; Cedervall, Tommy; Abdshill, Hodan LU ; Johansson, Fredrik and Englund Johansson, Ulrica LU (2014) In PLoS ONE 9(8).
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
9
issue
8
publisher
Public Library of Science
external identifiers
  • pmid:25144684
  • wos:000341106100058
  • scopus:84929196664
ISSN
1932-6203
DOI
10.1371/journal.pone.0105359
language
English
LU publication?
yes
id
2745680b-b40f-4a70-81e0-b6b2c0157938 (old id 4614216)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25144684?dopt=Abstract
date added to LUP
2014-09-08 20:53:43
date last changed
2017-11-05 03:55:45
@article{2745680b-b40f-4a70-81e0-b6b2c0157938,
  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.},
  articleno    = {e105359},
  author       = {Söderstjerna, Erika and Bauer, Patrik and Cedervall, Tommy and Abdshill, Hodan and Johansson, Fredrik and Englund Johansson, Ulrica},
  issn         = {1932-6203},
  language     = {eng},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Silver and gold nanoparticles exposure to in vitro cultured retina - studies on nanoparticle internalization, apoptosis, oxidative stress, glial- and microglial activity.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0105359},
  volume       = {9},
  year         = {2014},
}