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Effects of blue light on the circadian system and eye physiology
Open accessAbstract
Light-emitting diodes (LEDs) have been used to provide illumination in industrial and commercial environments. LEDs are also used in TVs, computers, smart phones, and tablets. Although the light emitted by most LEDs appears white, LEDs have peak emission in the blue light range (400-490 nm). The accumulating experimental evidence has indicated that exposure to blue light can affect many physiologic functions, and it can be used to treat circadian and sleep dysfunctions. However, blue light can also induce photoreceptor damage. Thus, it is important to consider the spectral output of LED-based light sources to minimize the danger that may be associated with blue light exposure. In this review, we summarize the current knowledge of the effects of blue light on the regulation of physiologic functions and the possible effects of blue light exposure on ocular health.
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![Figure 2 In addition to the classical photoreceptors (rods and cones), ipRGCs are present in the retina. Recent studies have shown that at least two types of intrinsically photosensitive retinal ganglion cells (ipRGCs) have been identified: M1 and M2. Most of the M1 cells project to the suprachiasmatic nucleus (SCN) of the hypothalamus whereas the number of M1 and M2 projecting to the olivary pretectal nucleus (OPN) is similar (55% from M1 cells versus 45% from M2 cells). The M1 cells are considerably smaller but respond with significantly larger depolarizations and light-induced currents than do the M2 cells. Other neural targets of ipRGCs not shown in the figure include the preoptic area, sub-paraventricular zone, anterior hypothalamic nucleus, lateral hypothalamus, medial amygdaloid nucleus, lateral habenula, lateral geniculate nucleus (dorsal division), bed nucleus of the stria terminalis, periaqueductal gray, and superior colliculus. OS=outer segments; IS=inner segments; ONL=outer nuclear layer; OPL=outer plexiform layer; INL=inner nuclear layer; IPL=inner plexiform layer; GCL=ganglion cell layer; from [31] with permission.](/paper-figures/265e812f0902416b9f950f4a4c95def6/effects-of-blue-light-on-the-circadian-system-and-eye-physiology-figure-2.jpg)
![Figure 3 Top panels. The exposure to blue light (λmax 474), green light (λmax 513), or fluorescent light at the intensity of 1×10−1 μW/cm2 for 4 h/day for 30 days did not produce a significant change in the number of cells in the photoreceptor layers of the Sprague-Dawley rats (n=6; see [121] for details about the methods used to quantify cells in the photoreceptor layer). Lower panels. The exposure to blue or green light-emitting diodes (LEDs) for 4 h in the middle of the day did not induce apoptosis. Terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay: 4- to 6-week-old Sprague-Dawley rats (n=6) were anesthetized (75 mg/kg ketamine and 23 mg/kg xylazine), kept on heating pads (37 °C), and exposed to blue or green light for 4 h. The pupils were dilated with 1% atropine and 2.5% phenylephrine eye drops 45 min before the light exposure. Rats were then killed 16 h after the exposure to blue light or green light. The eyes were explanted and fixed using freshly prepared 4% polyformaldehyde in PBS, pH 7.4 for 20 min at room temperature. They were washed 3X with PBS, permeabilized with freshly prepared 0.1% Triton X-100 in 0.1% sodium citrate for 2 min on ice (2–8 °C), and then the TUNEL reaction was performed according to the instructions included in the manual (In Situ cell Death Detection kit). The slides were incubated in a humidified container for 60 min at 37 °C in the dark. Slides were rinsed 3X with PBS, and samples were analyzed under a fluorescence microscope (Zeiss Axioskop).](/paper-figures/305433154706427aa9b8bfe542089554/effects-of-blue-light-on-the-circadian-system-and-eye-physiology-figure-3.jpg)
![Figure 4 Different light treatments did not affect rhodopsin mRNA levels (one-way ANOVA, p>0.1). Exposure to blue light (λmax 474) at the intensity of 1×10−1 μW/cm2 for 4 h/day for 30 days produced significant changes in the mRNA levels of short wavelength sensitive (SW) opsin, melanopsin, and medium wavelength sensitive opsin (* one-way ANOVA followed by Holm-Sidak tests, p<0.05). Rats were exposed to blue, green, or white light-emitting diodes (LEDs) every day (4 h) for 30 days in the middle of the day (11:00 to 15:00) and then returned to a 12 h:12 h light-dark cycle. The intensity of the light during the light phase of the 12 h:12 h light-dark cycle was about 400–450 lux. Every day, the pupils were dilated with 1% atropine and 2.5% phenylephrine eye drops 45 min before exposure to blue, green, or white light-emitting diodes (LEDs). After 30 days, the rats were killed, and the retinas were explanted, immediately frozen, and stored at −80 °C. mRNA was then extracted, and mRNA levels were measured using real-time quantitative PCR (qPCR; see [122] for details about primers and qPCR conditions).](/paper-figures/0cfaa61e316042d694a3d017c76d4cd2/effects-of-blue-light-on-the-circadian-system-and-eye-physiology-figure-4.jpg)
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“The severity of the blue‐light induced damage depends on the time of the day and is thus related with the circadian rhythm 52.”
From The inner clock-Blue light sets the human rhythm (2019) · cites this paper as [52]
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“While short wavelengths in the range of 460 nm are very efficient in phase shifting of circadian system, intensive blue light in the range between 400 and 440 nm (see Figure 4) is damaging to the retina via a photochemical reaction called photoreversal of bleaching 52.”
From The inner clock-Blue light sets the human rhythm (2019) · cites this paper as [52]
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“However, the detrimental effect of blue light on the retina should be taken with caution. Most of the damaging effects through blue light are demonstrated in nocturnal animals only, or in isolated animal cell cultures directly exposed to blue light 52, 53, 54.”
From The inner clock-Blue light sets the human rhythm (2019) · cites this paper as [52]
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“Accumulation of ROS and lipofuscin may be due to both acute and cumulative exposure to blue light 52.”
From The inner clock-Blue light sets the human rhythm (2019) · cites this paper as [52]
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“The amount of lipofuscin in the retina increases with age and is related to age‐related macular degeneration 52.”
From The inner clock-Blue light sets the human rhythm (2019) · cites this paper as [52]
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Citations
Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
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Phototransduction by retinal ganglion cells that set the circadian clock
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Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor
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A Novel Human Opsin in the Inner Retina
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Measuring and using light in the melanopsin age
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A retinohypothalamic projection in the rat
Moore, R. Y., & Lenn, N. J. (1972) · The Journal of Comparative Neurology · doi:10.1002/cne.901460102 · Cited by 1,263
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Metadata
- Authors
- Tosini, G., Ferguson, I., & Tsubota, K.
- Affiliations
- Morehouse School of Medicine (US)
- Missouri University of Science and Technology (US)
- Keio University (JP)
- Corresponding author
- Tosini, Gianluca
- Venue
- Molecular Vision
- Publisher
- Molecular Vision
- Published
- 2016-01
- Volume
- 22
- Pages
- 61-72
- ISSN
- 1090-0535 (ISSN-L)
- PMC
- PMC4734149
- OpenAlex
- W2294594166
- Cited by
- 517
- References
- 126
- Citations by year
- 2026: 52 · 2025: 51 · 2024: 43 · 2023: 51 · 2022: 54 · 2021: 54 · 2020: 103 · 2019: 42 · 2018: 37 · 2017: 27 · 2016: 3
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Molecular vision (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Aeronautics and Space Administration (NCC958)
- National Space Biomedical Research Institute (NCC 9‐58)
- National Institutes of Health (NCC9-58)
- National Eye Institute (R01EY022216)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Ophthalmology › Ocular and Laser Science Research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
- Keywords
- blue light, light-emitting diodes, circadian rhythm, circadian system, sleep disorders, photoreceptor damage, eye health, eye physiology, blue light exposure, light spectrum
- MeSH terms
- Animals, Circadian Rhythm, Humans, Light, Ocular Physiological Phenomena, Photic Stimulation, Photoreceptor Cells, Vertebrate
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