Photosensitive Melanopsin-Containing Retinal Ganglion Cells in Health and Disease: Implications for Circadian Rhythms

Lax, Pedro; Ortuño‐Lizarán, Isabel; Maneu, Victoria; Vidal‐Sanz, Manuel; Cuenca, Nicolás

doi:10.3390/ijms20133164

Cited by 47 publications

(37 citation statements)

References 145 publications

(201 reference statements)

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“…Post-mortem studies in aging populations above age 70 showed statistically significant age-dependent decrease in mRGC subtypes M1d and M3 cells, and trending changes in other mRGC subtypes [35, 40]. In one study in Parkinson’s disease by Ortuño-Lizarán and colleagues, the M1d was the most affected mRGC subtype, showing a decrease in M1d density as well as morphological changes [41, 42].…”

Section: Discussionmentioning

confidence: 99%

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

Amore

Sultan

et al. 2019

PLoS ONE

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BackgroundMelanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body’s circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD.MethodsWe performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm.ResultsOur results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls.ConclusionsThe variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.

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Section: Discussionmentioning

confidence: 99%

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

Amore

Sultan

et al. 2019

PLoS ONE

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“…The M1 subtype of ipRGCs integrates rods/cones and melanopsin signals to drive the non-image-forming effects of light. This subtype is very sensitive to dim, scotopic light and can mediate effects of dim light on sleep quality control [ 31 ]. Until now, data about the effects of ALAN on VLPO function are lacking, and it is not known if the VLPO sensitivity to ALAN is similar to that of SCN, which is reflected by the suppressed melatonin production.…”

Section: Discussionmentioning

confidence: 99%

Impact of Dim Light at Night on Urinary 6-Sulphatoxymelatonin Concentrations and Sleep in Healthy Humans

Stebelová

Roška

Zeman

2020

IJMS

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Artificial light at night can have negative effects on human wellbeing and health. It can disrupt circadian rhythms, interfere with sleep, and participate in the progress of civilisation diseases. The aim of the present study was to explore if dim artificial light during the entire night (ALAN) can affect melatonin production and sleep quality in young volunteers. We performed two experiments in real-life home-based conditions. Young volunteers (n = 33) were exposed to four nights of one lux ALAN or two nights of five lux ALAN. Melatonin production, based on 6-sulphatoxymelatonin/creatinine concentrations in urine, and sleep quality, based on actimetry, were evaluated. Exposure to ALAN one lux during the entire night did not suppress aMT6s/creatinine concentrations but did aggravate sleep quality by increasing sleep fragmentation and one-minute immobility. ALAN up to five lux reduced melatonin biosynthesis significantly and interfered with sleep quality, as evidenced by an increased percentage of one-minute immobility and a tendency of increased fragmentation index. Our results show that people are more sensitive to low illuminance during the entire night, as previously expected. ALAN can interfere with melatonin production and sleep quality in young, healthy individuals, and both processes have different sensitivities to light.

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“…A vicious circle may follow, also including a reduced self-chosen daytime activity, natural light exposure, and compromised sleep quality. In POAG and its progression, RGCs are damaged [ 23 , 26 , 27 , 28 , 29 ]; the process involves ipRGCs as well, though their damage occurs at more advanced disease stages [ 28 , 29 ]. Since ipRGCs are essential for non-visual signal transduction to the hypothalamic SCN, the central oscillator of the biological clock [ 30 ], the reception and transduction of light signaling are compromised.…”

Section: Discussionmentioning

confidence: 99%

“…Conditions of reduced quality of the transmission of entraining impulses to the SCN are prerequisites for altered light-driven synchronization of the circadian rhythms [ 23 , 24 ]. Damage to the ipRGCs is one of the factors predisposing to chronic circadian disruption and misalignment between the intrinsic biological clock and a principal external time cue such as light [ 23 , 24 , 29 ]. Internal phase misalignment has various adverse effects on physical and mental well-being and sleep parameters.…”

Section: Discussionmentioning

confidence: 99%

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma

Нероев

Малишевская

Weinert

et al. 2020

IJMS

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Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of “marker” circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.

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Photosensitive Melanopsin-Containing Retinal Ganglion Cells in Health and Disease: Implications for Circadian Rhythms

Cited by 47 publications

References 145 publications

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

Impact of Dim Light at Night on Urinary 6-Sulphatoxymelatonin Concentrations and Sleep in Healthy Humans

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma

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