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 retinal toxicity of MNPs, we determined whether MNPs (50nm and 4µm in diameter) affect intraocular pressure, alter retinal morphology, photoreceptor function, intraretinal cellular densities, and affect retinal astrogliosis patterns at different time points after eye injection. 44 Sprague-Dawley rats were injected with an equal volume (3µl) of 50nm or 4µm magnetic particles into the left eye, with an equal volume of PBS into the right eye as controls. Electroretinogram (ERG) was measured to determine whether MNPs could cause any functional changes to the photoreceptor layers. Animals were euthanized at 1hr, 1day, 1 week, 1month and 21weeks. Enucleated eyes were post fixed with 4% paraformaldehyde and sectioned for histologic examination. H&E, iron staining (Perl’s), and immunostaining against GFAP (for astrocytes and Muller glia) and CD11b (for microglia) was performed. Retinal nuclear layer cell densities were determined.
Results: :
Compared with control-injected eyes, MNPs do not significantly alter IOP measurements. ERG showed the amplitudes for the a-waves in 100-250µV range and b-waves in 500-600µV range, there are no significant differences between injected and non injected eyes. Histological sectioning and immunofluorescence staining showed little difference in MNPs injected animals vs. controls, although at 1 week, the corneal endothelial cell count was statistically lower in the 4µm particle group compared to the PBS or 50nm nanoparticle group.
Conclusions: :
Intravitreal or anterior chamber injections of MNPs showed little to no signs of toxicity on retinal structure, photoreceptor function or interference with aqueous drainage in the eye. Our results suggest that MNPs are safe for intraocular use.