title: Evaluation of magnetic micro- and nanoparticle toxicity to ocular tissues.
abstract: OBJECTIVE
  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.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Hemalatha B
authors.initials: HB
authors.lastname: Raju
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Anil
authors.initials: A
authors.lastname: Vedula
authors.forename: Sander R
authors.initials: SR
authors.lastname: Dubovy
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004596:Electroretinography; D005123:Eye / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005295:Ferrocyanides / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D008280:Magnetics; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
chemical_list: D005295:Ferrocyanides; D005904:Glial Fibrillary Acidic Protein; D007501:Iron; C000170:ferric ferrocyanide