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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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Iron deposits in the ocular tissues after particle injections.Representative images from Prussian blue histochemical staining for iron from control and magnetic particle-injected eyes at 1 week. Iron staining was observed only in the positive control, and not in any of the injected eyes, as marked. The 4 µm particles were visible in the iris and retinal tissues (arrows).
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pone-0017452-g007: Iron deposits in the ocular tissues after particle injections.Representative images from Prussian blue histochemical staining for iron from control and magnetic particle-injected eyes at 1 week. Iron staining was observed only in the positive control, and not in any of the injected eyes, as marked. The 4 µm particles were visible in the iris and retinal tissues (arrows).

Mentions: We stained histologic sections with Perl's Prussian Blue, and observed typical staining in the positive control tissues, as expected, but no staining was detected in any of the magnetic particle-injected eyes at 1 week (Figure 7). At 5 months after injection, iron staining was detected in the choroid for many of the animals, including in controls, which likely represents a normal feature of the aging choroid and thus was considered background (Figure 8). Other than this background choroidal staining, no iron staining was detected in any of the other ocular tissues after 50 nm MNP injections in the AC or vitreous. In contrast, in 4 µm particle injected eyes, iron staining was detected in the retina after IVT injection, and in the cornea and ciliary body after AC injection (Figure 8 and Table 2). Thus, by 5 months, iron deposition was only detected above background in the 4 µm particle-injected animals, but never in the 50 nm MNP-injected animals.


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

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

Iron deposits in the ocular tissues after particle injections.Representative images from Prussian blue histochemical staining for iron from control and magnetic particle-injected eyes at 1 week. Iron staining was observed only in the positive control, and not in any of the injected eyes, as marked. The 4 µm particles were visible in the iris and retinal tissues (arrows).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017452-g007: Iron deposits in the ocular tissues after particle injections.Representative images from Prussian blue histochemical staining for iron from control and magnetic particle-injected eyes at 1 week. Iron staining was observed only in the positive control, and not in any of the injected eyes, as marked. The 4 µm particles were visible in the iris and retinal tissues (arrows).
Mentions: We stained histologic sections with Perl's Prussian Blue, and observed typical staining in the positive control tissues, as expected, but no staining was detected in any of the magnetic particle-injected eyes at 1 week (Figure 7). At 5 months after injection, iron staining was detected in the choroid for many of the animals, including in controls, which likely represents a normal feature of the aging choroid and thus was considered background (Figure 8). Other than this background choroidal staining, no iron staining was detected in any of the other ocular tissues after 50 nm MNP injections in the AC or vitreous. In contrast, in 4 µm particle injected eyes, iron staining was detected in the retina after IVT injection, and in the cornea and ciliary body after AC injection (Figure 8 and Table 2). Thus, by 5 months, iron deposition was only detected above background in the 4 µm particle-injected animals, but never in the 50 nm MNP-injected animals.

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