Nanoceria inhibit the development and promote the regression of pathologic retinal neovascularization in the Vldlr knockout mouse
Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxid...
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Published in | PloS one Vol. 6; no. 2; p. e16733 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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Public Library of Science
22.02.2011
Public Library of Science (PLoS) |
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Abstract | Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxidative stress as a common node upstream of the blinding effects of these diseases. Knockout of the Vldlr gene results in a mouse that develops intraretinal and subretinal neovascular lesions within the first month of age and is an excellent model for a form of AMD called retinal angiomatous proliferation (RAP). Cerium oxide nanoparticles (nanoceria) catalytically scavenge ROS by mimicking the activities of superoxide dismutase and catalase. A single intravitreal injection of nanoceria into the Vldlr-/- eye was shown to inhibit: the rise in ROS in the Vldlr-/- retina, increases in vascular endothelial growth factor (VEGF) in the photoreceptor layer, and the formation of intraretinal and subretinal neovascular lesions. Of more therapeutic interest, injection of nanoceria into older mice (postnatal day 28) resulted in the regression of existing vascular lesions indicating that the pathologic neovessels require the continual production of excessive ROS. Our data demonstrate the unique ability of nanoceria to prevent downstream effects of oxidative stress in vivo and support their therapeutic potential for treatment of neurodegenerative diseases such as AMD and DR. |
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AbstractList | Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxidative stress as a common node upstream of the blinding effects of these diseases. Knockout of the Vldlr gene results in a mouse that develops intraretinal and subretinal neovascular lesions within the first month of age and is an excellent model for a form of AMD called retinal angiomatous proliferation (RAP). Cerium oxide nanoparticles (nanoceria) catalytically scavenge ROS by mimicking the activities of superoxide dismutase and catalase. A single intravitreal injection of nanoceria into the Vldlr-/- eye was shown to inhibit: the rise in ROS in the Vldlr-/- retina, increases in vascular endothelial growth factor (VEGF) in the photoreceptor layer, and the formation of intraretinal and subretinal neovascular lesions. Of more therapeutic interest, injection of nanoceria into older mice (postnatal day 28) resulted in the regression of existing vascular lesions indicating that the pathologic neovessels require the continual production of excessive ROS. Our data demonstrate the unique ability of nanoceria to prevent downstream effects of oxidative stress in vivo and support their therapeutic potential for treatment of neurodegenerative diseases such as AMD and DR. Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxidative stress as a common node upstream of the blinding effects of these diseases. Knockout of the Vldlr gene results in a mouse that develops intraretinal and subretinal neovascular lesions within the first month of age and is an excellent model for a form of AMD called retinal angiomatous proliferation (RAP). Cerium oxide nanoparticles (nanoceria) catalytically scavenge ROS by mimicking the activities of superoxide dismutase and catalase. A single intravitreal injection of nanoceria into the Vldlr-/- eye was shown to inhibit: the rise in ROS in the Vldlr-/- retina, increases in vascular endothelial growth factor (VEGF) in the photoreceptor layer, and the formation of intraretinal and subretinal neovascular lesions. Of more therapeutic interest, injection of nanoceria into older mice (postnatal day 28) resulted in the regression of existing vascular lesions indicating that the pathologic neovessels require the continual production of excessive ROS. Our data demonstrate the unique ability of nanoceria to prevent downstream effects of oxidative stress in vivo and support their therapeutic potential for treatment of neurodegenerative diseases such as AMD and DR. |
Audience | Academic |
Author | Zhou, Xiaohong Seal, Sudipta Karakoti, Ajay S Wong, Lily L McGinnis, James F |
AuthorAffiliation | 1 Department of Ophthalmology, University of Oklahoma, College of Medicine, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America University of Bristol, United Kingdom 2 Advanced Materials Processing Analysis Center, Mechanical Materials Aerospace Engineering, Nanoscience, and Technology Center, University of Central Florida, Orlando, Florida, United States of America 3 Department of Ophthalmology and Cell Biology, Oklahoma Center for Neuroscience, Oklahoma City, Oklahoma, United States of America |
AuthorAffiliation_xml | – name: 2 Advanced Materials Processing Analysis Center, Mechanical Materials Aerospace Engineering, Nanoscience, and Technology Center, University of Central Florida, Orlando, Florida, United States of America – name: University of Bristol, United Kingdom – name: 3 Department of Ophthalmology and Cell Biology, Oklahoma Center for Neuroscience, Oklahoma City, Oklahoma, United States of America – name: 1 Department of Ophthalmology, University of Oklahoma, College of Medicine, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America |
Author_xml | – sequence: 1 givenname: Xiaohong surname: Zhou fullname: Zhou, Xiaohong organization: Department of Ophthalmology, University of Oklahoma, College of Medicine, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America – sequence: 2 givenname: Lily L surname: Wong fullname: Wong, Lily L – sequence: 3 givenname: Ajay S surname: Karakoti fullname: Karakoti, Ajay S – sequence: 4 givenname: Sudipta surname: Seal fullname: Seal, Sudipta – sequence: 5 givenname: James F surname: McGinnis fullname: McGinnis, James F |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21364932$$D View this record in MEDLINE/PubMed |
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ContentType | Journal Article |
Copyright | COPYRIGHT 2011 Public Library of Science 2011 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Zhou et al. 2011 |
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Notes | Conceived and designed the experiments: XZ LLW ASK SS JFM. Performed the experiments: XZ ASK. Analyzed the data: XZ LLW ASK SS JFM. Wrote the paper: XZ LLW ASK SS JFM. Current address: Environmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, United States of America Current address: Massachusetts Eye and Ear Infirmary, Howe Laboratory, Harvard Medical School, Boston, Massachusetts, United States of America |
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SubjectTerms | Aerospace engineering Animals Antioxidants Apoptosis Biology Catalase Cerium Cerium - administration & dosage Cerium - pharmacology Cerium - therapeutic use Cerium oxides Diabetes mellitus Diabetic retinopathy Diabetic Retinopathy - drug therapy Diabetic Retinopathy - pathology Diabetic Retinopathy - prevention & control Disease Down-Regulation - drug effects Drug Evaluation, Preclinical Eye Eye - blood supply Eye - drug effects Eye - pathology Glaucoma House mouse Hypertension Inflammation Injection Intravitreal Injections Laboratories Lesions Low density lipoprotein receptors Macular degeneration Macular Degeneration - drug therapy Macular Degeneration - pathology Macular Degeneration - prevention & control Medical treatment Medicine Metabolism Metal Nanoparticles - administration & dosage Metal Nanoparticles - therapeutic use Mice Mice, Inbred C57BL Mice, Knockout Mimicry Nanoparticles Nervous system diseases Neurodegeneration Neurodegenerative diseases Neurological diseases Nitric oxide Oxidative stress Oxygen Photoreceptors Reactive oxygen species Reactive Oxygen Species - metabolism Receptors, LDL - genetics Receptors, LDL - physiology Retina Retinal degeneration Retinal Neovascularization - drug therapy Retinal Neovascularization - genetics Retinal Neovascularization - pathology Retinal Neovascularization - prevention & control Retinopathy Rodents Superoxide dismutase Superoxides Vascular endothelial growth factor Vascularization |
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Title | Nanoceria inhibit the development and promote the regression of pathologic retinal neovascularization in the Vldlr knockout mouse |
URI | https://www.ncbi.nlm.nih.gov/pubmed/21364932 https://www.proquest.com/docview/1296308887 https://pubmed.ncbi.nlm.nih.gov/PMC3043063 https://doaj.org/article/abb4226853cc44e3be341d7f88e35c02 http://dx.doi.org/10.1371/journal.pone.0016733 |
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