Joyce, D. S. | Search bioRxiv

bioRxiv2019

Duration invariance of the human circadian system response to pulsed light

The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterised by a delayed off-time following light offset. Here, we exploited this unusual physiologic property to characterise the exquisite sensitivity of the human circadian system to flashed light. In a 34-hour in-laboratory between-subjects design, we examined variable-intensity (3-9500 photopic lux; n=28 participants) full-field flashes at fixed duration (2 ms), and variable-duration (10 s-10 s) full-field flashes at fixed intensity (2000 photopic lux; n=31 participants) delivered using eye masks. We measured the circadian phase shift of the dim-light melatonin onset (DLMO) on the subsequent evening, acute melatonin suppression, objective alertness, and subjective sleepiness during the flash sequence. We find a clear dose-response relationship between flash intensity and the induced circadian phase shift, with an approximate increase of 10 minutes of phase delay for each ten-fold increase in photopic illuminance, but no parametric relationship between flash duration and induced circadian phase shift.

neuroscience↗

bioRxiv2017

Intrinsically photosensitive retinal ganglion cell mediated pupil function is impaired in Parkinson’s disease

Parkinsons disease is characterised by non-motor symptoms including sleep and circadian disruption, but the underlying aetiology is not well understood. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals from the eye to brain areas controlling circadian rhythms and the pupil light reflex. Here we evaluate the hypothesis that these non-motor symptoms in people with Parkinsons disease may be linked to ipRGC dysfunction. Using chromatic pupillometry, we measured intrinsic (melanopsin-mediated) ipRGC and extrinsic (rod/cone photoreceptor-mediated) inputs to the pupil control pathway in a group of optimally medicated participants with a diagnosis of Parkinsons disease (PD, n = 17) compared to controls (n = 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. The PD participants underwent additional clinical assessments using the Unified Parkinsons disease Rating Scale (UPDRS) and the Hoehn and Yahr scale (H&Y).\n\nCompared to controls, the PD group demonstrated an attenuated pupil constriction amplitude in response to long wavelength pulsed stimulation, and reduced post-illumination pupil response (PIPR) amplitude in response to both short wavelength pulsed and sinusoidal stimulation. In the PD group, PIPR amplitude did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, UPDRS or H&Y score, or medication dosage. Both groups exhibited similar pupillary unrest in darkness.\n\nWe show that melanopsin and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage Parkinsons disease. Given that the deficits are independent of clinical assessment severity and are observed despite optimal medication, the melanopsin-mediated PIPR may be a biomarker for the detection of Parkinsons disease and its continued monitoring in both medicated and unmedicated individuals.

neuroscience↗