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Evaluation of magnetic micro- and nanoparticle toxicity to ocular tissues.

Raju HB, Hu Y, Vedula A, Dubovy SR, Goldberg JL - PLoS ONE (2011)

Bottom Line: Compared to control-injected eyes, MNPs did not alter IOP measurements.ERG amplitudes for a-waves were in the 100-250 µV range and b-waves were in the 500-600 µV range, with no significant differences between injected and non-injected eyes.Our results suggest that MNPs are safe for intraocular use.

View Article: PubMed Central - PubMed

Affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.

ABSTRACT

Purpose: Magnetic nanoparticles (MNPs) may be used for focal delivery of plasmids, drugs, cells, and other applications. Here we ask whether such particles are toxic to ocular structures.

Methods: To evaluate the ocular toxicity of MNPs, we asked if either 50 nm or 4 µm magnetic particles affect intraocular pressure, corneal endothelial cell count, retinal morphology including both cell counts and glial activation, or photoreceptor function at different time points after injection. Sprague-Dawley rats (n = 44) were injected in the left eye with either 50 nm (3 µl, 1.65 mg) or 4 µm (3 µl, 1.69 mg) magnetic particles, and an equal volume of PBS into the right eye. Electroretinograms (ERG) were used to determine if MNPs induce functional changes to the photoreceptor layers. Enucleated eyes were sectioned for histology and immunofluorescence.

Results: Compared to control-injected eyes, MNPs did not alter IOP measurements. ERG amplitudes for a-waves were in the 100-250 µV range and b-waves were in the 500-600 µV range, with no significant differences between injected and non-injected eyes. Histological sectioning and immunofluorescence staining showed little difference in MNP-injected animals compared to control eyes. In contrast, at 1 week, corneal endothelial cell numbers were significantly lower in the 4 µm magnetic particle-injected eyes compared to either 50 nm MNP- or PBS-injected eyes. Furthermore, iron deposition was detected after 4 µm magnetic particle but not 50 nm MNP injection.

Conclusions: Intravitreal or anterior chamber injections of MNPs showed little to no signs of toxicity on retinal structure, photoreceptor function or aqueous drainage in the eye. Our results suggest that MNPs are safe for intraocular use.

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Related in: MedlinePlus

Measure of electroretinograms changes in response to magnetic particles.Electroretinograms taken at 9–14 weeks for 50 nm- and 4 µm-, AC- and IVT-injected animals, as well as control, uninjected animals, as marked. The solid line represents the average of the particle-injected left eyes for each group, and the dashed line represents the average of the PBS-injected right eyes for each group, except in the control animals (1st column) in which neither eye was injected. There was no significant difference in the a- and b-waves for the control (uninjected) and nano- and microparticle injected animals with either IVT or AC injections.
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pone-0017452-g009: Measure of electroretinograms changes in response to magnetic particles.Electroretinograms taken at 9–14 weeks for 50 nm- and 4 µm-, AC- and IVT-injected animals, as well as control, uninjected animals, as marked. The solid line represents the average of the particle-injected left eyes for each group, and the dashed line represents the average of the PBS-injected right eyes for each group, except in the control animals (1st column) in which neither eye was injected. There was no significant difference in the a- and b-waves for the control (uninjected) and nano- and microparticle injected animals with either IVT or AC injections.

Mentions: Histochemical detection of ocular iron deposition may not be very sensitive, so we also examined the electroretinogram (ERG), which can be suppressed by molecular iron inside the eye [8], [9], [10]. We compared the PBS-injected right eyes to the magnetic particle-injected left eyes for all animals, and examined an additional set of animals in which neither eye was injected. We found similar amplitude ranges for all groups: a-waves in 100–250 µV range and b waves in 500–600 µV range (Figure 9). There were no significant difference in the a- and b-waves for the control (uninjected) and nano- and microparticle injected animals with either IVT or AC injections.


Evaluation of magnetic micro- and nanoparticle toxicity to ocular tissues.

Raju HB, Hu Y, Vedula A, Dubovy SR, Goldberg JL - PLoS ONE (2011)

Measure of electroretinograms changes in response to magnetic particles.Electroretinograms taken at 9–14 weeks for 50 nm- and 4 µm-, AC- and IVT-injected animals, as well as control, uninjected animals, as marked. The solid line represents the average of the particle-injected left eyes for each group, and the dashed line represents the average of the PBS-injected right eyes for each group, except in the control animals (1st column) in which neither eye was injected. There was no significant difference in the a- and b-waves for the control (uninjected) and nano- and microparticle injected animals with either IVT or AC injections.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102660&req=5

pone-0017452-g009: Measure of electroretinograms changes in response to magnetic particles.Electroretinograms taken at 9–14 weeks for 50 nm- and 4 µm-, AC- and IVT-injected animals, as well as control, uninjected animals, as marked. The solid line represents the average of the particle-injected left eyes for each group, and the dashed line represents the average of the PBS-injected right eyes for each group, except in the control animals (1st column) in which neither eye was injected. There was no significant difference in the a- and b-waves for the control (uninjected) and nano- and microparticle injected animals with either IVT or AC injections.
Mentions: Histochemical detection of ocular iron deposition may not be very sensitive, so we also examined the electroretinogram (ERG), which can be suppressed by molecular iron inside the eye [8], [9], [10]. We compared the PBS-injected right eyes to the magnetic particle-injected left eyes for all animals, and examined an additional set of animals in which neither eye was injected. We found similar amplitude ranges for all groups: a-waves in 100–250 µV range and b waves in 500–600 µV range (Figure 9). There were no significant difference in the a- and b-waves for the control (uninjected) and nano- and microparticle injected animals with either IVT or AC injections.

Bottom Line: Compared to control-injected eyes, MNPs did not alter IOP measurements.ERG amplitudes for a-waves were in the 100-250 µV range and b-waves were in the 500-600 µV range, with no significant differences between injected and non-injected eyes.Our results suggest that MNPs are safe for intraocular use.

View Article: PubMed Central - PubMed

Affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.

ABSTRACT

Purpose: Magnetic nanoparticles (MNPs) may be used for focal delivery of plasmids, drugs, cells, and other applications. Here we ask whether such particles are toxic to ocular structures.

Methods: To evaluate the ocular toxicity of MNPs, we asked if either 50 nm or 4 µm magnetic particles affect intraocular pressure, corneal endothelial cell count, retinal morphology including both cell counts and glial activation, or photoreceptor function at different time points after injection. Sprague-Dawley rats (n = 44) were injected in the left eye with either 50 nm (3 µl, 1.65 mg) or 4 µm (3 µl, 1.69 mg) magnetic particles, and an equal volume of PBS into the right eye. Electroretinograms (ERG) were used to determine if MNPs induce functional changes to the photoreceptor layers. Enucleated eyes were sectioned for histology and immunofluorescence.

Results: Compared to control-injected eyes, MNPs did not alter IOP measurements. ERG amplitudes for a-waves were in the 100-250 µV range and b-waves were in the 500-600 µV range, with no significant differences between injected and non-injected eyes. Histological sectioning and immunofluorescence staining showed little difference in MNP-injected animals compared to control eyes. In contrast, at 1 week, corneal endothelial cell numbers were significantly lower in the 4 µm magnetic particle-injected eyes compared to either 50 nm MNP- or PBS-injected eyes. Furthermore, iron deposition was detected after 4 µm magnetic particle but not 50 nm MNP injection.

Conclusions: Intravitreal or anterior chamber injections of MNPs showed little to no signs of toxicity on retinal structure, photoreceptor function or aqueous drainage in the eye. Our results suggest that MNPs are safe for intraocular use.

Show MeSH
Related in: MedlinePlus