Ocular Control of Melatonin Regulation: Action Spectrum

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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.