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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

Localization of magnetic nanoparticles at 1 week.At 1 week after IVT injection, immunofluorescence was used to localize 50 nm particles (green in a) and 4 µm particles (red in b) as shown by white arrows. In both cases, retinas were counterstained with GFAP and DAPI (nuclei, blue). At 1 week, both sizes of magnetic particles were detectable in the ganglion cell layer (arrows). Scale bar, 50 µm.
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pone-0017452-g003: Localization of magnetic nanoparticles at 1 week.At 1 week after IVT injection, immunofluorescence was used to localize 50 nm particles (green in a) and 4 µm particles (red in b) as shown by white arrows. In both cases, retinas were counterstained with GFAP and DAPI (nuclei, blue). At 1 week, both sizes of magnetic particles were detectable in the ganglion cell layer (arrows). Scale bar, 50 µm.

Mentions: We could not detect 50 nm MNPs in histologic sections, but they were visible acutely after IVT injection in the GCL of the retina. At 1 week, 50 nm MNPs were detected without significant GFAP immunoreactivity (Figure 3a), whereas microparticles elicited significant GFAP upregulation (Figure 3b). No GFAP staining was detected in either group at 5 months (not shown). We found that there was no difference in the retinal nuclear cell density as measured along the GCL, INL and ONL at any time point from 1 week to 5 months (Figure 4a–b). Interestingly, we found that corneal endothelial cell numbers were no different between the control and 50 nm MNP AC-injected eyes, but there was a statistically significant decrease in corneal endothelial cell number in the eyes injected with 4 µm magnetic microparticles at 1 week and 5 months compared to PBS- and MNP-injected eyes (Figure 4b). Thus, 50 nm MNPs failed to detectably alter ocular histology, but magnetic microparticles were slightly toxic to the corneal endothelium.


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

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

Localization of magnetic nanoparticles at 1 week.At 1 week after IVT injection, immunofluorescence was used to localize 50 nm particles (green in a) and 4 µm particles (red in b) as shown by white arrows. In both cases, retinas were counterstained with GFAP and DAPI (nuclei, blue). At 1 week, both sizes of magnetic particles were detectable in the ganglion cell layer (arrows). Scale bar, 50 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017452-g003: Localization of magnetic nanoparticles at 1 week.At 1 week after IVT injection, immunofluorescence was used to localize 50 nm particles (green in a) and 4 µm particles (red in b) as shown by white arrows. In both cases, retinas were counterstained with GFAP and DAPI (nuclei, blue). At 1 week, both sizes of magnetic particles were detectable in the ganglion cell layer (arrows). Scale bar, 50 µm.
Mentions: We could not detect 50 nm MNPs in histologic sections, but they were visible acutely after IVT injection in the GCL of the retina. At 1 week, 50 nm MNPs were detected without significant GFAP immunoreactivity (Figure 3a), whereas microparticles elicited significant GFAP upregulation (Figure 3b). No GFAP staining was detected in either group at 5 months (not shown). We found that there was no difference in the retinal nuclear cell density as measured along the GCL, INL and ONL at any time point from 1 week to 5 months (Figure 4a–b). Interestingly, we found that corneal endothelial cell numbers were no different between the control and 50 nm MNP AC-injected eyes, but there was a statistically significant decrease in corneal endothelial cell number in the eyes injected with 4 µm magnetic microparticles at 1 week and 5 months compared to PBS- and MNP-injected eyes (Figure 4b). Thus, 50 nm MNPs failed to detectably alter ocular histology, but magnetic microparticles were slightly toxic to the corneal endothelium.

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