Visualizing the Next Steps in Parkinson Disease

Bódis-Wollner, Iván

doi:10.1001/archneur.59.8.1233

Cited by 19 publications

(6 citation statements)

References 14 publications

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“…PD patients display visual symptoms including dimness, blurring, blunted shapes, double vision and difficulty reading (Bodis-Wollner, 2002). However, visual symptoms specifically associated with DJ-1 mutations and deletions have not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…These mutations are hypothesized to induce a loss of the entire protein or loss-of-function versions of the protein (Bonifati et al, 2003), possibly by interfering with its homodimerization (Tao and Tong, 2003) or by forming unstable higher order complexes (Macedo et al, 2003, Knobbe et al, 2011). Visual symptoms such as dimness, blurring, blunted shapes, double vision and difficulty reading are common features in PD patients (Bodis-Wollner, 2002). However, the visual symptoms specifically attributed to PD patients carrying DJ-1/PARK7 mutations are not known.…”

Section: Introductionmentioning

confidence: 99%

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

Bonilha

Bell

Rayborn

et al. 2015

Experimental Eye Research

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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 were 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Bonilha

Bell

Rayborn

et al. 2015

Experimental Eye Research

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“…Although the hallmark of PD is impaired motor function, non-motor symptoms such as anxiety, depression, cognitive dysfunction, sleep disorders, and autonomic and gastrointestinal disturbances can also contribute to a decline in quality of life [1]. For example, visual dysfunction is a common cause of disability in PD [2], with clinical manifestations including photophobia, diplopia, altered visual acuity, dry eyes, visuospatial dysfunction, and complex visual hallucinations [3,4].…”

Section: Introductionmentioning

confidence: 99%

Progressive Changes in the Retinal Structure of Patients with Parkinson’s Disease

Mao

et al. 2018

Journal of Parkinson’s Disease

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“…Rather, the CS measure, which is in fact more relevant to everyday tasks, 31 shows specific changes. Consistent with the results of the electrophysiologic studies, the behaviorally measured CS is most reduced above 2 cpd.…”

Section: Primary Visual Impairments In Pd: the Retina And The Visual mentioning

confidence: 98%

Parkinson's Disease, Aging, and Visual Cognition

Antal

Terney

Bódis-Wollner

2008

Topics in Geriatric Rehabilitation

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Normal ageing results in a multitude of physiological changes that could contribute to sensory impairments not necessarily caused by a disease process. A distinction between aging and disease has a diagnostic and potential therapeutic relevance in Parkinson's disease (PD). In parallel with retinal deficits, a dopaminergic dysregulation of the fronto-striatal circuits may occur in PD. Several visual and visuo-cognitive deficits are not yet demarcated in PD from ageing. Nevertheless, select impairment of retinal spatio-temporal visual processing and specific visual categorization deficits in PD are the result of the disease, not of aging per se. Key words: aging, Parkinson's disease, visual and cognitive dysfunctions P ARKINSON'S DISEASE (PD) is known as a movement disorder that is characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies and resulting functional changes that involve all components of the frontostriatal circuits, thalamostriatal circuits, and related posterior cortical areas. In the last 2 decades, several studies have demonstrated that parallel with or beyond the progressive motor impairments, nonmotor symptoms are also prevalent, including primary visual, visuospatial, perceptual, visuomotor, and visuocognitive dysfunctions (for review, see references 1-6). While impaired vision is not a dominant symp-

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Visualizing the Next Steps in Parkinson Disease

Cited by 19 publications

References 14 publications

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

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

Progressive Changes in the Retinal Structure of Patients with Parkinson’s Disease

Parkinson's Disease, Aging, and Visual Cognition

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