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Since the advent of light-emitting diode (LED) technology, both the laboratory animal science community and lighting industry have embraced its use. While currently the most common light source used worldwide in vivaria and workplaces is broad-spectrum cool white fluorescent (CWF) lighting, LED lighting is rapidly emerging and has many advantages over both CWF (Figure 1) and incandescent lighting. These advantages include higher energy efficiency, lower heat production, superior spectral control, significantly longer operating life, solid state sturdiness, size, and reduced weight among others.1

Figure 1: Photo image showing typical luminaire with standard T8 soft, cool-white on left; and, one standard T8 LED lamp, high in blue-emissions on right. RT Dauchy, photoimage.

All in all, LED lighting offers a clear long-term, inexpensive alternative to conventional lighting. Nonetheless, while institutions worldwide are transitioning to this new technology, a paucity of information is available regarding the long-term use of daytime LED lighting and its potential influence on human and animal behavior, metabolism, and physiology.

Based on ours2 and other findings,3 in 2007 the World Health Organization classified exposure to broad-spectrum light-at-night (LAN) as a probable Class II carcinogen.4 A similar position was taken in 2009 by the American Cancer Society and again in 2012 by American Medical Association (AMA).5 Subsequently, in 2016 the AMA adopted a policy statement regarding the adverse effects of long-term exposure to blue-enriched LED light-at-night (LAN) having a color-correlated temperature (CCT) index of greater than 3,000K in the outside nighttime community setting. These adverse effects included disruption of various biological processes creating potential harmful effects associated with disability glare and sleep disturbance.

The AMA recommendation was for the use of LED lighting at nighttime with CCT lower than 3,000K (intensity, illuminance, and irradiance was not specified) and that attention be paid to design and engineering features that include proper shielding of light sources to reduce disability glare. LED light-at-day (LAD), and more specifically the most commonly used blue-enriched LED light-at-day (bLAD) was not addressed.

Here we discuss emerging evidence in support of the positive impact of daytime exposure to bLAD on the circadian regulation of neuroendocrine, metabolic, and physiologic parameters associated with the promotion of laboratory animal health and well-being.

Light: A Potent Stimulus
Light is arguably the most potent stimulus for influencing circadian, neuroendocrine, and neurobehavioral regulation in all mammals, which is closely associated with animal health and well-being and, in turn, impacts scientific outcomes. Hence, light intensity, duration of exposure, and spectral quality or wavelength, are all considerations to be factored into both facility design and experimental protocols when using animal models in research.

Evidence accrued over the past 30 years reveals that many aspects of mammalian physiology and behavior influenced by retinal illumination occur so via the non-visual system of the retinohypothalamic tract and not via the visual, image-forming system of the primary optic tract.

The suprachiasmatic nucleus (SCN), or ‘master biologic clock’ located in the hypothalamus of the brain, is entrained by the light-dark cycle. Photobiologic responses that include circadian rhythms of metabolism and physiology are mediated by small organic molecules, or chromophores, contained within a small subset of retinal cells called intrinsically photosensitive retinal ganglion cells (ipRGCs). Light quanta are detected in all mammals by the chromophore melanopsin contained within ipRGCs mostly in the lower-wavelength, blue-appearing portion of the visible spectrum (465 – 485 nm). Photic information is then transmitted to the SCN via the retinohypothalamic tract (Figure 2).

Figure 2: Photo image depicting how daytime blue-enriched LED light impacts circadian sensitivity, compared to broad spectrum CWF light (photopic sensitivity). RT Dauchy, photoimage.

The SCN regulates the daily pineal gland production of the circadian neurohormone melatonin, resulting in high levels at night and low levels during daytime. The daily, rhythmic melatonin signal temporally coordinates normal behavioral and physiologic functions associated with the promotion and animal health and well-being.

Benefits of Blue-Enriched LED Light
Previously we showed that rodents exposed to small changes in the spectral transmittance (color) of light during light phase experienced marked changes in the nighttime melatonin signal, leading to alterations in temporal coordination of metabolism and physiology.7 More specifically was the finding that nighttime melatonin levels in male pigmented nude rats exposed to blue-enriched light during daytime were over 6-fold higher than those exposed to broad-spectrum CWF light. The enhanced nighttime melatonin level markedly suppressed metabolism, signal transduction activity and growth of human prostate cancer xenografts in the rats.

In a subsequent study,8 animals exposed to daytime blue-enriched LED light (5,000 CCT; 2,650 lm; 165.3 ± 5.2 lx [67.2 ± 2.1 µW/cm2]) displayed nighttime melatonin levels over 7-fold higher, compared to those exposed to standard CWF light (4,100 CCT; 2,700 lm; 168.1 ± 5.4 lx [66.3 ± 2.1 µW/cm2]) (Figure 1).8 Circadian rhythms of arterial plasma levels of fatty acids, glucose, lactate and neuroendocrine hormones such as corticosterone, insulin, and leptin were generally lower over the course of a 24-h day. In addition, fat content was decreased and protein content elevated in over 10 major metabolic tissues as the animals aged, indicative of a younger, more healthy phenotype.

Taken together, exposure of rats to blue-enriched LED lighting during the daytime has a marked positive impact on metabolic and physiologic parameters associated with the promotion of animal health and well-being. Investigations now underway are examining these parameters in male and female mouse strains.

Meeting Research Needs
Prior to electrical lighting, societies around the world were more agricultural in nature exposed to blue-enriched sunshine during the daytime and limited-to-no LAN. In today’s 24-7 Westernized societies this reality is quite different. We are generally indoors for longer periods during the daytime and nighttime, and are routinely exposed to mostly broad spectrum CWF and LED in origin. With this in mind, it is somewhat easier to understand how normal mammalian circadian rhythms may be disrupted leading to increased incidence of human cancer and metabolic syndrome, which is now revealed in over 20 major epidemiological studies in night shift workers.3

The international lighting industry and laboratory animal science fields have established certain points to consider when deciding on lighting for both the workplace and animal facilities: lighting efficiency, lower heat production, superior spectral control, and long-term lower costs. We are also aware of how light intensity, spectral quality, and duration of light exposure influence virtually every major biological process associated with animal physiology and metabolism. Hence, appropriate lighting and lighting protocols influence animal health and well-being and the outcome of scientific investigations.

Current research suggests for both humans and laboratory animals that exposure to more blue-enriched light during daytime strongly reinforces normal circadian rhythmicity. Conversely, exposure at nighttime to light enriched more in the longer-wavelength emission (above 580 nm; amber, red) is most beneficial in this regard. Furthermore, during the normal dark phase in animal facilities and ‘nighttime’ sleep phase for humans it is important that rooms be completely devoid of LAN. Concomitantly, these lighting scenarios work to optimize intact circadian rhythmicity and health and well-being.

In a recent landmark report,9 Lucas and colleagues detail a new light measurement strategy and provide suggestions for artificial/architectural lighting regulatory authorities, lighting manufacturers, designers, and engineers. This includes daytime blue-enriched LED light measurements that independently quantify effective irradiance for each of the non-visual photoreceptive inputs involved in the entrainment of normal physiological and behavioral states. The authors argue that retinal irradiance should be increased during daytime within acceptable limits with light sources biased toward the blue regions of the visible spectrum, as is the case with the LED lights employed in our basic research studies.7,8

Our growing understanding regarding the use of daytime blue-enriched LED lighting in the vivarium, workplace, and home, with its superior spectral control and all other major advantages, compared to incandescent or CWF lighting, suggest it may be the best technology currently available to address these concerns. Additional studies are warranted to improve our understanding of the potential beneficial effects of daytime blue enriched LED lighting in optimizing control of animal health and well-being.

References

  1. Illuminating Engineering Society of North America. 2008. Light and human health: an overview of the impact of optical radiation on visual, circadian, neuroendocrine, and neurobehavioral responses. New York (NY): Illuminating Engineering Society.
  2. Blask DE, Brainard GC, Dauchy RT, Hanifin JP, Davidson LK, Krause JA, Sauer LA, Rivera-Bermudez MA, Dubocovich ML, Jasser SA, Lynch DT, Rollag MD, and Zalatan F. 2005. Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. Cancer Res 65: 11174-11184.
  3. Stevens RG, Brainard GC, Blask DE, Lockley SW, Motta ME. 2014. Breast cancer and circadian disruption from electric lighting in the modern world. CA Cancer J Clin 64: 207-2018.
  4. Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Altieri A, Benbrahim-Talla L, Cogliano V. 2007. Carcinogenicity of shift-work, painting, and fire-fighting. Lancet Oncol. 8: 1065-1066.
  5. Council on Science and Public Health Report 4. 2012. Light pollution. Adverse effects of nighttime lighting. American Medical Association, Annual Meeting, Chicago, IL.
  6. Council on Science and Public Health Report 2-A-16. 2016. Human and environmental effects of light emitting diode (LED) community lighting. American Medical Association, Annual Meeting, Chicago, IL.
  7. Dauchy RT, Wren-Dail MA, Hoffman AE, Hanifin JP, Warfield B, Brainard GC, Hill SM, Belancio VP, Dauchy EM, Blask DE. 2015. Daytime blue light enhances the nighttime circadian melatonin inhibition of human prostate cancer growth. Comp Med 65: 473-385.
  8. Dauchy RT, Wren-Dail MA, Hoffman AE, Hanifin JP, Warfield B, Brainard GC, Hill SM, Belancio VP, Dauchy EM, Blask DE. 2016. Effects of daytime exposure to light from blue-enriched light-emitting diodes on the nighttime melatonin amplitude of rodent metabolism and physiology. Comp Med 66(5): 373-383.
  9. Lucas RJ, Peirson SN, Berson DM, Brown TM, Cooper HM, Czeisler CA, Firueiro MG, Gamlin PD, Lockley SW, O’Hagan JB, Price LLA, Provencio I, Skene DJ, Brainard GC. 2014. Measuring and using light in the melanopsin age. Trends in Neurosci 37(1): 1-9.

Bob Dauchy, MS, RLATG, CMAR, is a cancer researcher and faculty member of Tulane University School of Medicine and the Manager of the Laboratory of Chrononeuroendocrine Oncology in the Department of Structural and Cellular Biology.

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