title: Nanoceria inhibit the development and promote the regression of pathologic retinal neovascularization in the Vldlr knockout mouse.
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.
authors.affiliation: Department of Ophthalmology, University of Oklahoma, College of Medicine, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhou
authors.forename: Lily L
authors.initials: LL
authors.lastname: Wong
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Karakoti
authors.forename: Sudipta
authors.initials: S
authors.lastname: Seal
authors.forename: James F
authors.initials: JF
authors.lastname: McGinnis
mesh_terms: D000818:Animals; D002563:Cerium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005123:Eye / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
chemical_list: D017382:Reactive Oxygen Species; D011973:Receptors, LDL; C036053:VLDL receptor; D002563:Cerium; C030583:ceric oxide