Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice

    Authors

    S. V. Kyosseva; L. J. Chen; S. Seal;J. F. McGinnis

    Comments

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    Abbreviated Journal Title

    Int. J. Photoenergy

    Keywords

    nanoceria; oxidative stress; inflammation; Vldlr mouse; age related; macular degeneration; PCR array; DENSITY LIPOPROTEIN RECEPTOR; CERIUM OXIDE NANOPARTICLES; ENDOTHELIAL; GROWTH-FACTOR; MACULAR DEGENERATION; ANGIOMATOUS PROLIFERATION; OXIDATIVE STRESS; SUBRETINAL NEOVASCULARIZATION; CHOROIDAL; NEOVASCULARIZATION; CORNEAL EPITHELIUM; UP-REGULATION; Ophthalmology

    Abstract

    Oxidative stress and inflammation are important pathological mechanisms in many neurodegenerative diseases, including age-related macular degeneration (AMD). The very low-density lipoprotein receptor knockout mouse (Vldlr-/-) has been identified as a model for AMD and in particular for retinal angiomatous proliferation (RAP). In this study we examined the effect of cerium oxide nanoparticles (nanoceria) that have been shown to have catalytic antioxidant activity, on expression of 88 major cytokines in the retinas of Vldlr-/- mice using a PCR array. A single intravitreal injection of nanoceria at P28 caused inhibition of pro-inflammatory cytokines and pro-angiogenic growth factors including Tslp, Lif, Il3, Il7, Vegfa, Fgf1, Fgf2, Fgf7, Egf, Efna3, Lep, and up-regulation of several cytokines and anti-angiogenic genes in the Vldlr-/- retina within one week. We used the Ingenuity Pathway Analysis software to search for biological functions, pathways, and interrelationships between gene networks. Many of the genes whose activities were affected are involved in cell signaling, cellular development, growth and proliferation, and tissue development. Western blot analysis revealed that nanoceria inhibit the activation of ERK 1/2, JNK, p38 MAP kinase, and Akt. These data suggest that nanoceria may represent a novel therapeutic strategy to treat AMD, RAP, and other neurodegenerative diseases. (C) 2013 Elsevier Ltd. All rights reserved.

    Journal Title

    Experimental Eye Research

    Volume

    Exp. Eye Res.

    Publication Date

    1-1-2013

    Document Type

    Article

    Language

    English

    First Page

    63

    Last Page

    74

    WOS Identifier

    116

    ISSN

    0014-4835

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