Ocular Control of Melatonin Regulation: Action Spectrum

描述(由申请人提供)：研究表明，光疗法可以 有效地治疗选定的睡眠障碍和重新引导昼夜节律 与倒班工作或洲际航空挑战相关的生理学 旅行。一份国会报告估计，2000万人口 美国轮班工人的健康问题增加，包括 睡眠减少，神经行为能力降低，罹患 心血管和胃肠疾病。这项工作的长期目标是 确定临床负责的昼夜节律光感受器(S) 光疗法对人类的益处。 目前，还不知道哪种感光剂能为 光的昼夜节律和治疗效果。目前的工作旨在 识别负责褪黑激素光调节的光色素(S) 通过研究参与急性发作的光的光谱特征 褪黑素的昼夜节律抑制和相移 人类。实现这一目标的主要技术将是动作谱 分析。行动谱：1)定义了 激发生物反应的波长，以及2)有助于识别 光感受器参与了这种反应。在过去的四年里，一个8 健康人光诱导褪黑素抑制的波长作用谱 一种适用于感光色素的维生素A1视神经的志愿者已经被开发出来 光谱最大值(波长max)在464 nm处的诺模图。的具体目标 这一建议是为了：1)检验来自以下数据的通量响应数据的假设 单色波长400和420 nm对褪黑素的抑制作用 色觉正常的志愿者将适合464 nm的维生素A1视功能 诺模图。2)检验褪黑素的光感受器假设 对明视视觉的调节不依赖于光感受器 急性光诱导褪黑素抑制的作用谱比较 色觉正常的受试者和视锥系统受试者 先天性斜视和近视的缺陷。3)检验这一假设 急性褪黑素抑制和褪黑素节律的相移是 通过测试褪黑素的相移，波长敏感度相似 暴露于等光子密度的单色激光后的昼夜节律 正常人的波长分别为464 nm和555 nm。最终，这项研究将 导致鉴定涉及使用光的光感受器 一种治疗性干预。

DESCRIPTION (provided by applicant): Studies have shown light therapy to be effective in treating selected sleep disorders and re-entraining circadian physiology relative to the challenges of shift work or intercontinental air travel. A Congressional report estimates that the population of 20 million shift workers in the U.S. suffers from increased health problems including reduced sleep, reduced neurobehavioral performance, and higher risk of cardiovascular and gastrointestinal disease. The long term goal of this work is to identify the circadian photoreceptor(s) responsible for the clinical benefits of light therapy in humans. Currently, it is not known which photopigments transduce light stimuli for the circadian and therapeutic effects of light. The present work is aimed toward identifying the photopigment(s) responsible for light regulation of melatonin by investigating the spectral characteristics of light involved in acute melatonin suppression and phase shifting of the circadian melatonin rhythm in humans. The primary technique to accomplish this aim will be action spectrum analysis. An action spectrum: 1) defines the relative effectiveness of wavelengths for eliciting a biological response, and 2) helps to identify the photoreceptor involved in that response. Over the past four years, an 8 wavelength action spectrum for light-induced melatonin suppression in healthy volunteers has been developed which fits a vitamin A1 opsin photopigment nomogram with a spectral maximum (lambda max) at 464 nm. The specific aims of this proposal are to: 1) Test the hypothesis that fluence-response data from melatonin suppression with monochromatic wavelengths at 400 and 420 nm in volunteers with normal color vision will fit the 464 nm vitamin A1 opsin nomogram. 2) Test the hypothesis that the photoreceptor for melatonin regulation is independent of the photoreceptors for photopic vision by comparing action spectra for acute light-induced melatonin suppression in subjects with normal color vision and subjects who have the cone system deficiencies of deuteranopia and protanopia. 3) Test the hypothesis that both acute melatonin suppression and phase-shifting of the melatonin rhythm are similar in wavelength sensitivity by testing phase-shifts of the melatonin circadian rhythm following exposure to equal photon densities of monochromatic light at 464 nm and 555 nm in normal subjects. Ultimately, this research will lead to the identification of photoreceptors implicated in the use of light as a therapeutic intervention.