Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis/survival signaling pathways

    Authors

    L. Kong; X. Cai; X. H. Zhou; L. L. Wong; A. S. Karakoti; S. Seal;J. F. McGinnis

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Neurobiol. Dis.

    Keywords

    Nanoceria; Tubby mouse; Inherited retinal degeneration; Oxidative; stress; Apoptosis; Neuroprotection; FIBROBLAST-GROWTH-FACTOR; INHERITED RETINAL DEGENERATION; N-TERT-BUTYLNITRONE; CERIUM OXIDE NANOPARTICLES; LIGHT-INDUCED DAMAGE; MOUSE RETINA; OXIDATIVE STRESS; GENE-EXPRESSION; RAT RETINA; IN-VIVO; Neurosciences

    Abstract

    Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities which mimic those of the neuroprotective enzymes superoxide dismutase and catalase. We have previously shown that nanoceria preserve retinal morphology and prevent loss of retinal function in a rat light damage model. In this study, the homozygous tubby mutant mouse, which exhibits inherited early progressive cochlear and retinal degeneration, was used as a model to test the ability of nanoceria to slow the progression of retinal degeneration. Tubby mice were injected systemically, intracardially, with 20 mu l of 1 mM nanoceria in saline, at postnatal day 10 and subsequently at P20 and P30 whereas saline injected and uninjected wild type (or heterozygous tubby) served as injected and uninjected controls, respectively. Assays for retinal function, morphology and signaling pathway gene expression were performed on P34 mice. Our data demonstrate that nanoceria protect the retina by decreasing Reactive Oxygen Species (ROS), up-regulating the expression of neuroprotection-associated genes; down-regulating apoptosis signaling pathways and/or up-regulating survival signaling pathways to slow photoreceptor degeneration. These data suggest that nanoceria have significant potential as global agents for therapeutic treatment of inherited retinal degeneration and most types of ocular diseases. (C) 2011 Elsevier Inc. All rights reserved.

    Journal Title

    Neurobiology of Disease

    Volume

    42

    Issue/Number

    3

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    514

    Last Page

    523

    WOS Identifier

    WOS:000290081700031

    ISSN

    0969-9961

    Share

    COinS