Affiliations: [a] Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia
| [b] School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, Australia
| [c] Centre for Vision and Eye Research, Queensland University of Technology (QUT), Brisbane, Australia
Queensland Eye Institute (QEI), Brisbane, Australia
| [e] School of Optometry and Vision Sciences, Queensland University of Technology (QUT), Brisbane, Australia
| [f] Movement Neuroscience Program, Queensland University of Technology (QUT), Brisbane, Australia
Correspondence to: Beatrix Feigl, MD, PhD, Medical Retina Laboratory, Institute of Health and Biomedical Innovation, QUT. 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia. E-mail: [email protected].
Abstract: Background:Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) signal the environmental light to mediate circadian photoentrainment and sleep-wake cycles. There is high prevalence of circadian and sleep disruption in people with Parkinson’s disease; however, the underlying mechanisms of these symptoms are not clear. Objective:Based on the recent evidence of anatomical and functional loss of melanopsin ganglion cells in Parkinson’s disease, we evaluate the link between melanopsin function, circadian, and sleep behavior. Methods:The pupil light reflex and melanopsin-mediated post-illumination pupil response were measured using chromatic pupillometry in 30 optimally medicated people with Parkinson’s disease and 29 age-matched healthy controls. Circadian health was determined using dim light melatonin onset, sleep questionnaires, and actigraphy. Ophthalmic examination quantified eye health and optical coherence tomography measured retinal nerve fiber layer thickness. Results:The melanopsin-mediated post-illumination pupil response amplitudes were significantly reduced in Parkinson’s disease (p < 0.0001) and correlated with poor sleep quality (r2 = 33; p < 0.001) and nerve fiber layer thinning (r2 = 0.40; p < 0.001). People with Parkinson’s disease had significantly poorer sleep quality with higher subjective sleep scores (p < 0.05) and earlier melatonin onset (p = 0.01). Pupil light (outer retinal) response metrics, daily light exposure and outer retinal thickness were similar between the groups (p > 0.05). Conclusion:We demonstrate evidence-based mechanisms through which inner retinal ipRGC dysfunction contributes to sleep disruption in Parkinson’s disease in the presence of normal outer retinal (rod-cone photoreceptor) function. Our findings provide a rationale for designing new treatment approaches in Parkinson’s disease through melanopsin photoreceptor-targeted light therapies for improving sleep-wake cycles.