Abstract
PurposeMagnetic 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.MethodsTo 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.ResultsCompared 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.ConclusionsIntravitreal 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.
Highlights
Nanotechnology is an exciting new platform for translating advances in the basic sciences to therapeutics for eye disease
3 animals were studied per group, but intraocular pressure (IOP) and histology data for PBS-injected right eyes were pooled into groups irrespective of left eye treatment. *1 month survival groups were only subjected to histology and iron staining, not IOP or immunofluorescence measurements. **A set of uninjected animals was used exclusively for ERG measurements
Intraocular pressure We first asked whether injection of magnetic particles led to an increase in intraocular pressure (IOP)
Summary
Nanotechnology is an exciting new platform for translating advances in the basic sciences to therapeutics for eye disease. The nanoscale size of particles may confer advantageous properties for applications in drug delivery, gene therapy and cell and tissue engineering. Nanoparticles are well-suited to provide sustained drug delivery or gene therapy by virtue of highly controllable surface-area to volume ratios and improved tissue penetration [1]. Delivering drug, genetic, or cellular therapeutics efficaciously to internal ocular structures is a persistent challenge in ophthalmology. Drug delivery to the retina is limited by inadequate scleral tissue penetration, and recently increasing use of intravitreal injections leads to patient inconvenience and increased infection risk. Cell replacement therapies are limited by inadequate methods both to deliver cells to the targeted ocular tissue and to retain the transplanted cells until integration. Nanoparticle-based therapeutics may provide one such approach
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