Ocular Control of Melatonin Regulation: Action Spectrum

描述（由申请人提供）：研究表明， 有效治疗选定的睡眠障碍和重新引导昼夜节律 生理学相对于轮班工作或洲际空气的挑战 出行一份国会报告估计， 美国轮班工人的健康问题越来越多， 睡眠减少，神经行为表现降低， 心血管和胃肠道疾病。这项工作的长期目标是 识别负责临床的昼夜光感受器， 光疗法对人类的好处 目前，还不知道哪些色素会抑制光刺激， 昼夜节律和光的治疗效果。目前的工作是针对 鉴定负责褪黑激素的光调节的色素 通过研究急性脑梗死患者的光的光谱特性， 褪黑激素抑制和褪黑激素昼夜节律的相移 人类实现这一目标的主要技术是作用谱 分析.一个行动谱：1）定义相对有效性 用于引发生物反应的波长，以及2）有助于识别 光感受器参与这种反应。在过去的四年里，8 健康人光诱导褪黑激素抑制的波长作用光谱 志愿者已经开发出一种适合维生素A1的视蛋白色素 在464 nm处具有光谱最大值（λ max）的列线图。的具体目标 这一建议是：1）测试的假设，通量响应数据从 在400和420 nm的单色波长下， 具有正常色觉的志愿者将适合464 nm的维生素A1视蛋白 列线图2)测试褪黑激素的感光器 调节是独立于光感受器的明视视觉， 比较急性光诱导褪黑激素抑制的作用光谱， 具有正常色觉的受试者和具有视锥系统的受试者 绿盲和原盲的缺陷。3)检验假设， 急性褪黑激素抑制和褪黑激素节律的相移是 通过测试褪黑激素的相移 暴露于等光子密度的单色光后的昼夜节律 在正常受试者中在464 nm和555 nm处的光。最终，这项研究将 导致识别涉及光的使用的光感受器， 治疗干预

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.