title: Defining the catalytic activity of nanoceria in the P23H-1 rat, a photoreceptor degeneration model.
abstract: OBJECTIVE
  Inorganic catalytic nanoceria or cerium oxide nanoparticles (CeNPs) are bona fide antioxidants that possess regenerative radical scavenging activities in vitro. Previously, we demonstrated that CeNPs had neuroprotective and anti-angiogenic properties in rodent retinal degeneration and neovascularization models. However, the cellular mechanisms and duration of the catalytic activity of CeNPs in preventing photoreceptor cell loss are still unknown. In this study, we sought to answer these questions using the P23H-1 rat, an autosomal dominant retinitis pigmentosa (adRP) model.
  
  
  METHODS
  A single dose of either saline or CeNPs was delivered intravitreally into the eyes of P23H-1 rats at 2-3 weeks of age. Retinal functions were examined at 3 to 7 weeks post injection. We quantified retinal proteins by Western blot analyses and counted the number of apoptotic (TUNEL+) profiles in the outer nuclear layer (ONL) of retinal sections. We measured free 8-isoprostanes to quantify lipid peroxidation in retinal tissues.
  
  
  RESULTS
  We observed increased rod and cone cell functions up to three weeks post injection. Apoptotic cells were reduced by 46%, 56%, 21%, and 24% at 3, 7, 14, 21 days, respectively, after CeNPs injection compared to saline. Additionally, reduction of lipid peroxidation in the retinas of CeNPs-treated vs saline-treated animals was detected 14 days post injection.
  
  
  CONCLUSIONS
  We validated that CeNPs were effective in delaying loss of photoreceptor cell function in an adRP rat model. This represents the fourth rodent retinal disease model that shows delay in disease progression after a single application of CeNPs. We further demonstrated that CeNPs slowed the rate of photoreceptor cell death. We deduced that the catalytic activity of CeNPs in vivo in this rat model to be undiminished for at least 7 days and then declined over the next 14 days after CeNPs administration.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, College of Medicine, and Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America.
authors.forename: Lily L
authors.initials: LL
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, College of Medicine, and Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America.
authors.forename: Quentin N
authors.initials: QN
authors.lastname: Pye
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, College of Medicine, and Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Advanced Materials Processing Analysis Center, Materials Science and Engineering, Nanoscience and Technology Center, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Seal
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, College of Medicine, and Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America; Department of Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Graduate College, Oklahoma City, Oklahoma, United States of America.
authors.forename: James F
authors.initials: JF
authors.lastname: McGinnis
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D002563:Cerium / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D058449:Intravitreal Injections; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D002563:Cerium; C030583:ceric oxide
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