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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
High Impact Research and Research Infrastructure Programs (RC2)
Project #
1RC2HL101340-01
Application #
7853110
Study Section
Special Emphasis Panel (ZHL1-CSR-A (O2))
Program Officer
Lewin, Daniel S
Project Start
2009-09-30
Project End
2011-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$642,690
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Rahman, Shadab A; St Hilaire, Melissa A; Chang, Anne-Marie et al. (2017) Circadian phase resetting by a single short-duration light exposure. JCI Insight 2:e89494
Klerman, Elizabeth B; Wang, Wei; Phillips, Andrew J K et al. (2017) Statistics for Sleep and Biological Rhythms Research. J Biol Rhythms 32:18-25
Swaminathan, Krithika; Klerman, Elizabeth B; Phillips, Andrew J K (2017) Are Individual Differences in Sleep and Circadian Timing Amplified by Use of Artificial Light Sources? J Biol Rhythms 32:165-176
Bianchi, Matt T; Phillips, Andrew J K; Wang, Wei et al. (2017) Statistics for Sleep and Biological Rhythms Research. J Biol Rhythms 32:7-17
Bermudez, Eduardo B; Klerman, Elizabeth B; Czeisler, Charles A et al. (2016) Prediction of Vigilant Attention and Cognitive Performance Using Self-Reported Alertness, Circadian Phase, Hours since Awakening, and Accumulated Sleep Loss. PLoS One 11:e0151770
Klerman, Elizabeth B; Beckett, Scott A; Landrigan, Christopher P (2016) Applying mathematical models to predict resident physician performance and alertness on traditional and novel work schedules. BMC Med Educ 16:239
Lane, Jacqueline M; Chang, Anne-Marie; Bjonnes, Andrew C et al. (2016) Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology. Diabetes 65:1741-51
Bendrick, Gregg A; Beckett, Scott A; Klerman, Elizabeth B (2016) Human fatigue and the crash of the airshipItalia. Polar Res 35:
Vijayan, Sujith; Klerman, Elizabeth B; Adler, Gail K et al. (2015) Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia. J Neurophysiol 114:1923-30
Faghih, Rose T; Dahleh, Munther A; Adler, Gail K et al. (2015) Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing. IEEE Trans Biomed Eng 62:2379-88

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