Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinson’s disease

Ortuño‐Lizarán, Isabel; Esquiva, Gema; Beach, Thomas G.; Serrano, Geidy E.; Adler, Charles H.; Lax, Pedro; Cuenca, Nicolás

doi:10.1186/s40478-018-0596-z

Cited by 67 publications

(66 citation statements)

References 57 publications

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“…Insomnia is associated with reduced brain activation, blood flow, or glucose metabolism. There is a growing body of evidence that sleep disruption may also accelerate the progression of pathology of neurodegenerative diseases via defective mitochondrial dynamics and axonal transport [28]. The RNFL is found more sensitive to vascular changes associated with gliosis and inflammation than other layers of the retina, which would influence OCT measurements [29].…”

Section: Discussionmentioning

confidence: 99%

Insomnia Might Influence the Thickness of Choroid, Retinal Nerve Fiber and Inner Plexiform Layer

et al. 2020

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Sleep may play a fundamental role in retinal regulation and the degree of retinal variables. However, no clinical study has investigated optical coherence tomography (OCT) parameters in patients with primary insomnia. All participants were evaluated with the insomnia severity index (ISI) and the Pittsburgh sleep quality index (PSQI). The retinal nerve fiber layer (RNFL), ganglion cell layer (GC), inner plexiform layer (IPL), macula and choroidal (CH) thickness were compared between 52 drug-naïve patients with primary insomnia and 45 age-gender-BMI-smoke status matched healthy controls (HC). The patients with primary insomnia differed from the HC regarding RNFL-Global (p = 0.024) and RNFL-Nasal inferior (p = 0.010); IPL-Temporal (p < 0.001), IPL-Nasal (p < 0.001); CH-Global (p < 0.001), CH-Temporal (p = 0.004), CH-Nasal (p < 0.001), and CH-Fovea (p = 0.019). ISI correlated with RNFL-Global and RNFL-Nasal inferior. The regression analysis revealed that ISI was the significant predictor for the thickness of RNFL- Nasal inferior (p = 0.020), RNFL-Global (p = 0.031), and CH-Nasal (p = 0.035) in patients with primary insomnia. Sleep disorders are seen commonly in patients with psychiatric, including ocular diseases. Adjusting the effect of insomnia can help to clarify the consistency in findings of OCT.

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Section: Discussionmentioning

confidence: 99%

Insomnia Might Influence the Thickness of Choroid, Retinal Nerve Fiber and Inner Plexiform Layer

et al. 2020

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“…33 Finally, the rabbit polyclonal antimelanopsin antiserum (gift from Dr Provencio) was raised against the 15 N-terminal amino acids of the human melanopsin protein and has been characterized by immunohistochemistry in the human retina. 11,34 Cellular Quantification…”

Section: Antibody Characterizationmentioning

confidence: 99%

“…2,3 In addition, PD patients present several visual symptoms, such as reduced amplitudes in b-waves and oscillatory potentials on electroretinograms (ERGs), reduced visual evoked potentials, inner retinal layer thinning by optical coherence tomography (OCT), 4 impaired motion perception, contrast sensitivity, and color discrimination, [5][6][7][8] circadian rhythm dysfunction, 9,10 and melanopsin-containing retinal ganglion cell (mRGC) degeneration. 11 Considering the described similarities between the neurodegenerative process in the retina and brain, it is natural to wonder whether the dopaminergic cells in the retina are involved in the disease as they are in the brain. In the retina, dopamine is an essential neuromodulator that has widespread influences on retinal function and regulation.…”

Section: Introductionmentioning

confidence: 99%

Dopaminergic Retinal Cell Loss and Visual Dysfunction in Parkinson Disease

Ortuño‐Lizarán

Sánchez‐Sáez

Lax

et al. 2020

Annals of Neurology

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Objective: Considering the demonstrated implication of the retina in Parkinson disease (PD) pathology and the importance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic amacrine cells and some of their main postsynaptic neurons in the retina of PD. Methods: Using immunohistochemistry and confocal microscopy, we evaluated morphology, number, and synaptic connections of dopaminergic cells and their postsynaptic cells, AII amacrine and melanopsin-containing retinal ganglion cells, in control and PD eyes from human donors. Results: In PD, dopaminergic amacrine cell number was reduced between 58% and 26% in different retinal regions, involving a decline in the number of synaptic contacts with AII amacrine cells (by 60%) and melanopsin cells (by 35%). Despite losing their main synaptic input, AII cells were not reduced in number, but they showed cellular alterations compromising their adequate function: (1) a loss of mitochondria inside their lobular appendages, which may indicate an energetic failure; and (2) a loss of connexin 36, suggesting alterations in the AII coupling and in visual signal transmission from the rod pathway. Interpretation: The dopaminergic system impairment and the affection of the rod pathway through the AII cells may explain and be partially responsible for the reduced contrast sensitivity or electroretinographic response described in PD. Also, dopamine reduction and the loss of synaptic contacts with melanopsin cells may contribute to the melanopsin retinal ganglion cell loss previously described and to the disturbances in circadian rhythm and sleep reported in PD patients. These data support the idea that the retina reproduces brain neurodegeneration and is highly involved in PD pathology.

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“…In more advanced PD, behavioral factors such as a sedentary lifestyle with limited sunlight exposure may also weaken the circadian system . Furthermore, anatomical abnormalities in PD, such as optic neuropathy and loss of retinal ganglion cells, may weaken photic entrainment …”

Section: Normal Sleep–wake Mechanisms and Aberrations In Pdmentioning

confidence: 99%

“…26 Furthermore, anatomical abnormalities in PD, such as optic neuropathy and loss of retinal ganglion cells, may weaken photic entrainment. 29,30…”

Section: Normal Sleep-wake Mechanisms and Aberrations In Pdmentioning

confidence: 99%

Practical Evaluation and Management of Insomnia in Parkinson's Disease: A Review

Wallace

Wohlgemuth

Trotti

et al. 2020

Movement Disord Clin Pract

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Background Insomnia is one of the most common nonmotor features of Parkinson's disease (PD). However, there are few practical guidelines for providers on how to best evaluate and treat this problem. Methods and Findings This review was developed to provide clinicians with a pragmatic approach to assessing and managing insomnia in PD. Recommendations were based on literature review and expert opinion. We addressed the following topics in this review: prevalence of insomnia in PD, sleep–wake mechanisms, theoretical models of insomnia, risk factors, assessment, pharmacologic and nonpharmacologic treatments. Insomnia treatment choices may be guided by PD severity, comorbidities, and patient preference. However, there is limited evidence supporting pharmacotherapy and nonpharmacologic treatments of insomnia in PD. Conclusions We provide a pragmatic algorithm for evaluating and treating insomnia in PD based on the literature and our clinical experience. We propose personalized insomnia treatment approaches based on age and other issues. Gaps in the existing literature and future directions in the treatment of insomnia in PD are also highlighted.

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Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinson’s disease

Cited by 67 publications

References 57 publications

Insomnia Might Influence the Thickness of Choroid, Retinal Nerve Fiber and Inner Plexiform Layer

Insomnia Might Influence the Thickness of Choroid, Retinal Nerve Fiber and Inner Plexiform Layer

Dopaminergic Retinal Cell Loss and Visual Dysfunction in Parkinson Disease

Practical Evaluation and Management of Insomnia in Parkinson's Disease: A Review

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