Human circadian sensitivity to very short light pulses

描述(由申请人提供)： 哺乳动物的眼睛既有视觉功能，也有非成像功能。直到最近，临床和研究的注意力都集中在视觉功能上。然而，新的工作已经开始描述非成像反应的解剖学和生理学特征。其中一些反应是由于光对昼夜节律的影响，昼夜节律是由下丘脑视交叉上核(SCN)的起搏器产生的内源性~24小时节律。这种起搏器使用主要由固有的感光视网膜神经节细胞而不是视杆和视锥感光细胞介导的眼部光刺激来适应环境时间。SCN的输出影响几乎所有的生理功能，包括睡眠的时间和内容、激素释放、心血管和胃肠功能、神经认知客观表现、主观警觉性和情绪。昼夜节律起搏器或其与当地时间的正常相位关系的中断，如夜间或轮换工作班次或时差，与疾病、错误和事故有关。眼光暴露的其他非视觉影响包括褪黑素抑制(季节性生殖变化的信号)、瞳孔反射以及心率、表现和警觉性的变化。因为光是对这些功能最有效的刺激，所以了解光的哪些特性是最有效的是很重要的。我们将使用实验、建模和数据库方法来完成光持续时间的剂量响应曲线。在实验上，我们将量化持续2分钟和12分钟的眼睛光刺激的影响-以前被认为太短而没有效果的刺激，但可能会引起显著的生理变化。我们还将调查重置昼夜节律敏感度所需的黑暗暴露时间。还将研究光对其他功能的影响，包括褪黑素抑制、心率和警觉性。这些实验的数据将与2000多名受试者的数据结合在一起，这些数据已经在类似的方案中进行了研究，研究了光的持续时间、强度、时间和波长对人类昼夜节律起搏器、褪黑素抑制、心率、认知反应和睡眠的影响。然后，所有这些数据将被用来完善我们验证的光对人体昼夜节律起搏器影响的数学模型，该模型将与对策应用程序一起在互联网上提供。这项工作对于理解人体对眼光刺激的生理、激素、心率、表现和警觉性功能的基本生理学是相关的，这对视网膜/眼睛护理、老年人的睡眠以及改变的表现/警觉性具有重要意义。如果非常短的光刺激是有效的，那么眼部光刺激作为应对糟糕表现和警觉性的对策将比目前认为的更适用于更多的情况。这些结果可以用来预测光线的影响，提出暴露于光线或避免光线的建议，以及设计环境照明(例如，房间或台灯)，从而改善健康和警觉性，减少错误和事故。 公共卫生相关性： 哺乳动物的眼睛既有视觉功能，也有非成像功能。关于眼睛的非成像解剖学和生理学的新信息揭示了眼部光刺激对人类昼夜节律、褪黑素抑制、心率、瞳孔反射、认知表现、警觉性和睡眠的影响。这项拟议工作的结果可用于预测光的影响，提出涉及暴露于光或避免光的建议，并设计环境照明，从而提高健康和警觉性，减少错误和事故。

DESCRIPTION (provided by applicant): The mammalian eye serves both visual and non-image-forming functions. Until recently, clinical and research attention has focused on visual function. However, new work has begun to characterize the anatomy and physiology of the non-image-forming responses. Some of these responses are due to the effect of light on circadian rhythms, the endogenous ~24-hour rhythms generated by a pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. This pacemaker is entrained to environmental time using ocular light stimuli primarily mediated by intrinsically photosensitive retinal ganglion cells, rather than rod and cone photoreceptors. The outputs of the SCN influence almost every physiologic function, including the timing and content of sleep, hormone release, cardiovascular and gastrointestinal function, neurocognitive objective performance, subjective alertness, and mood. Disruption of the circadian pacemaker or of its normal phase relationship with local time, such as with night or rotating work shifts or jet lag, is associated with illness, errors and accidents. Other non-visual effects of ocular light exposure include melatonin suppression (signal for seasonal reproductive changes), pupillary reflexes, and changes in heart rate, performance, and alertness. Because light is the most potent stimulus for these functions, it is important to understand what characteristics of light are most effective. We will complete a dose response curve for light duration using experimental, modeling, and database approaches. Experimentally, we will quantify the effects of ocular light stimuli of 2 and 12 minute durations - stimuli that were previously considered too short to have an effect, but may induce significant physiologic changes. We also will investigate the duration of darkness exposure required to reset circadian sensitivity. The effects of light on other functions, including melatonin suppression, heart rate, and alertness will also be studied. The data from these experiments will be combined into a database with data from over 2000 subjects already studied in similar protocols on the effects of light duration, intensity, timing and wavelength on the human circadian pacemaker, melatonin suppression, heart rate, cognitive responses and sleep. All these data then will be used to refine our validated mathematical model of the effects of light on the human circadian pacemaker, which, with countermeasure applications, will be made available on the internet. This work is relevant for understanding the basic physiology of human circadian, hormone, heart rate, performance and alertness functions in response to ocular light stimuli, with implications for retinal/eye care; sleep of older persons; and altered performance/ alertness. If very short light stimuli are effective, then ocular light stimuli as countermeasures for poor performance and alertness would be applicable in more situations than currently believed. The results can be used to make predictions about the effects of light, to make recommendations involving exposure to or avoidance of light, and to design environmental lighting (e.g., room or desk lights), resulting in improved health and alertness and decreased errors and accidents. PUBLIC HEALTH RELEVANCE: The mammalian eye serves both visual and non-image-forming functions. New information about the non- image-forming anatomy and physiology of the eye has revealed effects of ocular light stimuli on human circadian rhythms, melatonin suppression, heart rate, pupillary reflexes, cognitive performance, alertness and sleep. The results of the proposed work can be used to make predictions about the effects of light, to make recommendations involving exposure to or avoidance of light, and to design environmental lighting, resulting in improved health and alertness and decreased errors and accidents.