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

Abstract

AbstractParkinson’s 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 Parkinson’s 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 Parkinson’s 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 Parkinson’s disease Rating Scale (UPDRS) and the Hoehn and Yahr scale (H&Y).Compared 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.We show that melanopsin and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage Parkinson’s 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 Parkinson’s disease and its continued monitoring in both medicated and unmedicated individuals.