Ocular input for human melatonin regulation 

 
George C. Brainard (1), Robert Levin (2) 
 
(1) Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA; (2) 
OSRAM SYLVANIA, Salem, MA, USA; E-mail: George.Brainard@mail.tju.edu 
 
It has been hypothesized that increased risk of breast cancer in industrialized countries is 
partially due to increased exposure to light at night which reduces melatonin production 
(Stevens and Rea, 2001).  To assess this hypothesis, it is important to understand how the 
human eye transduces light stimuli for melatonin regulation.  In both animals and humans, 
more light is required to activate the circadian and neuroendocrine systems than to stimulate 
the visual system.  Initially, it was thought that light of at least 2500 lux was needed to 
regulate melatonin secretion from the human pineal gland.  When exposure is carefully 
controlled, however, illuminances as low as 1.3 lux of monochromatic blue light at 460 nm or 
100 lux of broadband white light can significantly (p<0.01) suppress melatonin in humans 
(Brainard et al., 1997; 2001).  Similarly, a white light illuminance of 119 lux or lower can 
phase shift the human melatonin rhythm (Zeitzer et al., 2000). To understand how these lower 
illuminances can regulate melatonin in humans, it is necessary to examine the relevant ocular 
physiology that mediates this photic effect.  These ocular elements include: 1) gaze behavior, 
2) ocular lens age, 3) pupillary dilation, 4) photopigment and photoreceptor sensitivity, 5) 
photoreceptor location within the retina, 6) photoreceptor adaptation and 7) the ability of the 
circadian system to integrate photic stimuli spatially and temporally.  Recent findings suggest 
that a novel, nonvisual photopigment located in the ganglion cell layer of the retina is the 
primary regulator of melatonin and circadian  rhythms (Provencio et al., 2000; Brainard et al., 
2001; Berson et al., 2002; Hattar et al., 2002). Given the increasing exposure of citizens to 
light during the night in industrialized countries, it is useful from both a scientific as well as a 
clinical perspective to elucidate the photosensory physiology in the eye for melatonin 
regulation.  
 
Supported by grants from NIH RO1NS36590, National Space Biomedical Research Institute 
under NASA Cooperative Agreement NCC 9-58, and the Illuminating Engineering Society 
Philadelphia Chapter. 
 
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