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.

中文翻译：

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黑视素细胞功能障碍与帕金森病的睡眠中断有关

背景：表达黑视素的内在光敏视网膜神经节细胞 (ipRGC) 向环境光发出信号，以介导昼夜节律光诱捕和睡眠-觉醒周期。帕金森病患者的昼夜节律和睡眠中断的发生率很高；然而，这些症状的潜在机制尚不清楚。目的：基于最近关于帕金森病黑视蛋白神经节细胞解剖和功能丧失的证据，我们评估了黑视蛋白功能、昼夜节律和睡眠行为之间的联系。方法：使用彩色瞳孔测量法测量 30 名最佳药物治疗帕金森病患者和 29 名年龄匹配的健康对照组的瞳孔光反射和黑视蛋白介导的光照后瞳孔反应。使用昏暗的褪黑激素发作确定昼夜节律健康，睡眠问卷和活动记录。眼科检查量化眼睛健康和光学相干断层扫描测量视网膜神经纤维层厚度。结果：黑视蛋白介导的光照后瞳孔反应幅度在帕金森病患者中显着降低（p < 0.0001），并与睡眠质量差（r2 = 33；p < 0.001）和神经纤维层变薄（r2 = 0.40；p < 0.001）。帕金森病患者的睡眠质量明显较差，主观睡眠评分较高（p < 0.05），褪黑激素作用较早（p = 0.01）。瞳孔光（外视网膜）反应指标、每日光照和外视网膜厚度在各组之间相似（p > 0.05）。结论：我们展示了基于证据的机制，通过这些机制，在正常外视网膜（视杆锥光感受器）功能存在的情况下，内部视网膜 ipRGC 功能障碍有助于帕金森病的睡眠中断。我们的研究结果为通过黑视素光感受器靶向光疗法设计帕金森病的新治疗方法提供了理论依据，以改善睡眠-觉醒周期。