Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased oxidative stress in mice

Vera L. Bonilha, Brent A. Bell, Mary E. Rayborn, Xiaoping Yang, Charlie Kaul, Gregory H. Grossman, Ivy S. Samuels, Joe G. Hollyfield, Chengsong Xie, Huaibin Cai, Karen G. Shadrach

    Research output: Contribution to journalArticlepeer-review

    Abstract

    DJ-1/PARK7 mutations or deletions cause autosomal recessive early onset Parkinson's disease (PD). Thus, DJ-1 protein has been extensively studied in brain and neurons. PD patients display visual symptoms; however, the visual symptoms specifically attributed to PD patients carrying DJ-1/PARK7 mutations are not known. In this study, we analyzed the structure and physiology of retinas of 3- and 6-month-old DJ-1 knockout (KO) mice to determine how loss of function of DJ-1 specifically contributes to the phenotypes observed in PD patients. As compared to controls, the DJ-1 KO mice displayed an increase in the amplitude of the scotopic ERG b-wave and cone ERG, while the amplitude of a subset of the dc-ERG components was decreased. The main structural changes in the DJ-1 KO retinas were found in the outer plexiform layer (OPL), photoreceptors and retinal pigment epithelium (RPE), which were observed at 3 months and progressively increased at 6 months. RPE thinning and structural changes within the OPL were observed in the retinas in DJ-1 KO mice. DJ-1 KO retinas also exhibited disorganized outer segments, central decrease in red/green cone opsin staining, decreased labeling of ezrin, broader distribution of ribeye labeling, decreased tyrosine hydroxylase in dopaminergic neurons, and increased 7,8-dihydro-8-oxoguanine-labeled DNA oxidation. Accelerated outer retinal atrophy was observed in DJ-1 KO mice after selective oxidative damage induced by a single tail vein injection of NaIO3, exposing increased susceptibility to oxidative stress. Our data indicate that DJ-1-deficient retinas exhibit signs of morphological abnormalities and physiological dysfunction in association with increased oxidative stress. Degeneration of RPE cells in association with oxidative stress is a key hallmark of age-related macular degeneration (AMD). Therefore, in addition to detailing the visual defects that occur as a result of the absence of DJ-1, our data is also relevant to AMD pathogenesis.

    Original languageEnglish (US)
    Pages (from-to)22-36
    Number of pages15
    JournalExperimental eye research
    Volume139
    DOIs
    StatePublished - Oct 1 2015

    Keywords

    • Biochemistry
    • DJ-1 knockout
    • Histology
    • Immunohistology
    • Morphology
    • Oxidation
    • Physiology
    • Retina

    ASJC Scopus subject areas

    • Ophthalmology
    • Sensory Systems
    • Cellular and Molecular Neuroscience

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