Abstract
Light exposure has been proven to significantly impact human health, and
as a result, researchers are increasingly exploring its potential
benefits and drawbacks. With the advancements in understanding light and
the manufacturing of light sources, modern health lighting has become
widely utilized in daily life and plays a critical role in the
prevention and treatment of various illnesses. The use of light in
healthcare is a global trend, and many countries are actively promoting
the development and application of relevant scientific research and
medical technology. This field has gained worldwide attention and
support from scientists and doctors alike. In this review, we examine
the application of lighting in human health and recent breakthroughs in
light exposure related to pathology, therapeutic strategies, molecular
changes, and more. Finally, we also discuss potential future
developments and areas of application.
Key Words : Light exposure; Human health; Therapeutic
strategies; Phototherapy
Introduction
Light has always had a significant impact on human health. With
advancements in lighting technology, light-emitting diodes (LED) lamps
have become the preferred option, replacing traditional incandescent and
fluorescent lamps. This progression has led to improvements in energy
efficiency, extended service life and less negative environmental
impact. In addition to providing illumination, light has therapeutic
qualities that can aid in healing. For instance, sunlight has long been
used to treat skin diseases and rickets. In recent times, research has
broadened our understanding of light, including its effects on our
sleep-wake cycle, cognitive function, alertness and mood. Despite this,
overexposure to light, primarily at nighttime, can interfere with our
circadian rhythms, resulting in numerous health complications such as
sleep disorders, obesity, diabetes, and cancer. Consequently, scientists
are searching for solutions that will optimize the benefits of light
while minimizing harm. Furthermore, researchers are investigating the
potential of phototherapy to treat depression and other mood-related
conditions as well as photodynamic therapy for combating cancer cells.
Light is an essential component of human life, and its application takes
various forms. The development of light sources has progressed from
radiation lamp, gas discharge light to light emitting diode device.
Additionally, based on the specific application, the optimal spectrum
and intensity of light sources can significantly affect people’s lives.
Table 1 and figure 1 provides a summary of commonly used light sources
in medical applications, categorized based on their radiation
principles. The origins of electric light sources can be traced back to
the early 19th century when electrical laboratories utilized spark
discharges to create luminance; however, the results were low in
brightness and difficult to regulate. As a result, scientists began
exploring more effective methods for producing light. The vacuum light
bulb, an invention of Thomas Edison, utilized a vacuum to generate an
electrically powered, brilliant light source. Although there were
limitations in terms of brightness, the vacuum bulb was the first of its
kind and revolutionized the field of electric lighting. Discharge tube
is a device that utilizes gas discharge to generate vibrant light, which
can vary in color depending on the gas used, such as hydrogen, oxygen,
or neon. The introduction of discharge tubes is considered to be a
significant advancement in the progression of electric lighting. Gas
discharge lamps also utilize discharge to create a highly efficient and
bright light source. Gas discharge lamps, including neon, argon,
helium-neon mixed gas, and sodium lamp, among others, are widely used in
medical care, transportation, communication, and lighting. These lamps
play an essential role in meeting modern society’s needs for various
applications. Semiconductor light sources, such as LEDs and laser diodes
(LDs), are the most prominent electric light sources in the current
market. These sources are characterized by their long lifespan, high
efficiency, and adjustability, making them suitable for various
applications, including lighting, signaling, and display fields. For
example, incandescent lamps with very low cost and high color rendering
index are often used for illumination of operating tables, while high
penetration and high energy lasers are used for optical coherence
tomography (OCT) and excitation fluorescence staining. Notably, LEDs
with spectral flexibility are the best light source for PDT.[27]
The effect of light on organisms is spectral selective, meaning that
different biological tissues absorb different wavelengths of light, and
once absorbed, different wavelengths of light have varying effects on
organisms due to their different efficiencies in biological tissues.
Table 2 summarizes the primary conclusions that have been drawn so far.
Ultraviolet (UV) light functions primarily because of its high energy,
which is utilized for killing pathogens and exciting fluorescence. When
compared to concurrent UV light, blue light has a therapeutic effect due
to its limited penetration and is therefore helpful in treating acne and
other external bacterial infections. Green light plays a crucial role in
activating and inhibiting cytokines, regulating cell proliferation, and
migration. Red light primarily activates ATP, reducing inflammation,
treating pain, restoring damaged tissues, and helping treat cancer and
muscle recovery. It also restores cell elasticity in medical aesthetics
and promotes ribonucleotide enzymes to prevent age-induced macular
degeneration. Laser, with its high energy and focus, is mainly used in
surgical procedures and for scar removal.
Prolonged exposure to intense light can lead to eye strain, blindness,
cataracts, and other eye problems. In addition, the UV rays from the sun
can damage the skin, resulting in sunburn, skin aging, skin cancer, and
other issues. Light pollution can also have an adverse effect on human
health, leading to poor sleep quality, eye strain, anxiety, and more.
Therefore, it is crucial to take measures to protect oneself from the
sun and other sources of intense light. To prevent the negative effects
of light on human health and make the most of its potential for treating
diseases, it is essential to gain a deep understanding of the molecular
mechanisms through which light affects human cells and the principles of
existing controllable light applications. This paper reviews the
application, principle and progress of light in the field of health in
recent ten years.
Molecular mechanisms of light
affecting human health
Possible molecular mechanisms of light affecting human health include
promote vitamin D synthesis, regulation of endocrine and biological
rhythms, induction of oxidative stress, and DNA damage. Changes in
artificial lighting or sun light may have an impact on human health
through those mechanisms .
Promote vitamin D synthesis: During exposure to sunlight, UVB
photons with energies of 290-315 nm[90] are absorbed by
7-dehydrocholesteraol that is present in keratinocytes and dermal
fibroblasts. The absorption results in the rearrangement of the double
bonds and opening of the B ring leading to the formation of pre-vitamin
D3, which nonenzymatically isomerizes into the vitamin D3. Vitamin D3
which is produced by keratinocytes and fibroblasts diffuses into the
capillary bed and transported by the serum glycoprotein GC to the liver.
Vitamin D3 is converted to 25-hydroxyvitamin D3[25(OH)D3] by the
enzyme CYP2R1 in the liver and transported by the circulation to the
kidney. The enzyme CYP27B1 in the kidney is expressed and converts the
25-hydroxyvitamin D3[25(OH)D3] to 1α,25-dihydroxyvitamin D3
(1,25(OH)2D3). 1,25(OH)2D3 regulates calcium metabolism through
enhancing the expression of the epithelial calcium channel (ECaC) and
the calbindin 9K and stimulating the expression of receptor activator of
NFKB ligand (RANKL) in the osteoblasts.
Regulation of endocrine and biological rhythms: Light is
transmitted into the hypothalamus to regulate the function of the
hypothalamic-pituitary-target gland axis by stimulating nerve impulses
produced by the retina. Stimulated by light, hypothalamus releases
gonadotropin-releasing hormone (GnRH) through neural pathway, activates
the secretion of pituitary gonadotropin (FSH, LH), and promotes the
development and secretion of ovaries and testis. In addition, light can
directly or indirectly regulate the secretion of endocrine substances
such as thyroxine, adrenaline and insulin, thus affecting human
metabolism and growth and development, for example, UVB exposure induces
the release of ghrelin from skin adipocytes to enhance food-seeking
behavior.[91] In general, the regulation effect of light on
endocrine and biological rhythms is very complex, and the specific
mechanism needs further study.[92]
Oxidative stress: Another mechanism of light damage causes
oxidative stress and is unrelated to circadian rhythms. Exposure to
light has been proven to increase the expression of significant genes
that are not involved in circadian rhythms because they do not continue
to rhythmic cyclic change under constant darkness .[93] Recent
research conducted on C. elegans has demonstrated that oxidative stress
is the etiology of the shortened lifespan caused by visible light, and
the effects can be mitigated by antioxidants .[94] Light has been
demonstrated to induce oxidative stress and damage to lipids, proteins,
and DNA in other studies.[95, 96] Exposure to the visible light
exerted photodamage on mammalian liver cells, including inactivation of
catalase and lysosomal enzymes.[97] Reactive oxygen species (ROS) is
produced by UVA and bolus additions of
H2O2 as with the blue light, the blue
light photons are absorbed by the flavin-proteins, the superoxide is
produced by the absorption and reacted with nitric oxide to generate the
peroxynitrite[98]. Another way to oxidative stress is singlet
oxygen, the riboflavin as the photosensitizer absorbs the energy of
light and generate the singlet oxygen to increase the rate of ageing.
Blue light absorption is probably due to the presence of porphyrin and
leading to adenosine triphosphate (ATP) levels mobility significantly
reduced blue light reduces the activity of Complex II in the electron
transport system in both young and old flies.[36, 99] blue light,
which has been shown to be most effective in suppressing melatonin
secretion during the day to affect circadian rhythm.[38]
DNA damage: The harmful impact of UVA on living organisms can
be explained by the occurrence of type II oxygen-mediated photodynamic
reactions. When exposed to UVA, the production of reactive oxygen
species (ROS) is increased in the presence of photosensitizing
chromophores such as nicotinamide adenine dinucleotide phosphate
(NADPH), porphyrins, or flavins. As a result of this ROS production,
DNA, lipids, and proteins of cellular organisms are damaged.
Specifically, DNA photodamages are induced by UVB and UVC, which can
lead to mutations. UVB and UVC radiation cause two primary types of DNA
damage which are cis-cyclobutane pyrimidine dimers and pyrimidine
pyrimidone photoproducts. Furthermore, studies have revealed that even
light sources with minimal UV and blue wavelengths can induce pyrimidine
dimers in DNA. For instance, incandescent light that is devoid of UV and
most blue wavelengths can still cause pyrimidine dimers in DNA.[100]
Additionally, significant DNA strand breaks in mammalian cells are
induced by exposure to fluorescent light at 1000 lux for three
hours.[101]
Cell and animal models for light studies
For both cells and animals, light can affect their physiological
functions and overall survival. Light can activate specific cellular
responses, like light-sensitive cells in the retina that can sense light
and trigger a visual response. Additionally, light is critical for
regulating the circadian rhythm and physiological functions in animals.
It can manipulate the biological clock and metabolic state by affecting
the pineal gland and hypothalamus tissues in the brain, for example.
Moreover, light can impact animal behavior, seasonal reproductive
behavior, and more. Common studies involving light with cellular or
animal models usually include:
Human skin light model: The impact of light on the skin is the
most direct and noticeable. The skin light model is an experimental
method used for studying the interaction between light and skin. Its
primary applications are in the prevention and treatment of skin cancer,
as well as in the research and development of skin care products. In the
future, dermatological diagnoses based on the skin light model may lead
to significant advancements and breakthroughs.
Human cell: The main types of human cells used in light studies
are skin cells and fibroblasts. Skin cells, including epidermal cells
and melanocytes, are commonly utilized to investigate the effects of
light on these cells, such as sun damage, aging, and hyperpigmentation.
Research has demonstrated that light can induce DNA damage, enhance cell
death and aging, and increase the likelihood of skin cancer.[102,
103] Therefore, studying the impact of light on skin cells is crucial
for the development of skin health care and the treatment of skin
diseases. Fibroblasts are the most common connective tissue cells in the
body and are frequently used in light studies.[104, 105] Studies
have revealed that light has a notable effect on the proliferation and
differentiation of fibroblasts and can regulate the extracellular matrix
produced by them. Moreover, light can influence the rate and quality of
fiber tissue repair by altering fibroblast differentiation and matrix
synthesis, thereby influencing wound healing and scar formation. Other
cells, including various tumor cells and stem cells, have also been
examined in regards to light exposure.[106]
Skin light models in rats: Compared to human skin, rat skin is
more responsive and produces an inflammatory response to light, making
it an ideal subject for studying different light doses and wavelengths.
Nonetheless, it is important to take into consideration the
characteristics of rat skin, such as the thickness of its stratum
corneum and the density of keratinocytes. The biological responses of
rat skin to different wavelengths of light vary. For instance, UVB can
induce keratinocyte and epidermal cell apoptosis, while UVA can affect
cytochrome P450 (CYP450) activity and cell growth, leading to DNA damage
and inflammatory responses.[107] Therefore, studying rat skin light
models is crucial in exploring photosensitivity, skin inflammation, and
neoplastic lesions.[108-112] In the future, we must continue to
refine rat skin light models and apply them to various fields, including
medicine, drug development, and cosmetology.
Skin light models in mice: Single exposures can simulate acute
light damage, while multiple exposures are more similar to the long-term
light exposure that humans experience. The skin of mice exhibits
different biological responses to various wavelengths and doses of
light. The mouse skin light model plays a crucial role in exploring skin
inflammation, neoplastic lesions, immune response, and other related
factors.[110, 113-115] This model has found extensive applications
in life sciences, medical research, beauty, and other domains.
Zebrafish: The zebrafish is a commonly used model animal in
biomedical research, and its skin light model is an important research
subject in photobiology. The zebrafish light model can be categorized
into single-exposure, short-term repeated exposure, or long-term
repeated exposure. By adjusting the duration and intensity of light,
varying doses of UV, visible, and infrared radiation can be simulated.
When stimulated by light, the zebrafish skin exhibits a range of
biological reactions, including cell damage, inflammation, immune
response, and DNA damage repair.[105, 116] Different wavelengths and
doses of light elicit different responses. Moreover, zebrafish can be
used to study the effects of light on early embryonic development and
neural behavior.[117, 118] Due to its repeatability,
controllability, and ease of operation, the zebrafish skin light model
serves as an effective experimental model for researching skin
photobiological mechanism.
Elegans: Caenorhabditis elegans is a commonly used model
organism in life science research due to its simple and complete nervous
system, fully sequenced genome, short life cycle, and ease of mass
culture. The light model of C. elegans utilizes various light sources,
including white light, blue light, red light, and UV light, with
different time and intensity settings to simulate different doses of
light radiation. C. elegans exhibits responses to changes in light
intensity and wavelength, affecting growth, behavior, and metabolism.
For instance, nematodes display slower growth rates and longer lifespans
under lower light intensity than higher light intensity.[119-121]
Additionally, C. elegans uses photoreceptors to regulate protein
synthesis and lethal levels.[122] The light model of C. elegans can
aid in exploring the molecular and gene mechanisms of C. elegans’
responsiveness to light stimulation. Researchers can search for pivotal
genes involved in light response and further investigate their functions
and interactions in C. elegans.[123, 124]
Models of light related biological clocks, sleep and
wakefulness: Mice are one of the most commonly used models in studying
the biological clock. This is because they have a similar clock system
to humans, but are smaller in scale, have a shorter life cycle, and are
cheap and easy to obtain. Studies have shown that the physiological
features of mice, such as activity, body temperature, hormone levels,
and metabolism, can be regulated by changing their light exposure.
Researchers can manipulate the lighting conditions to study the
properties and mechanisms of the circadian clock in fruit flies. For
instance, they can vary the length and intensity of light and dark
cycles to determine how the biological clocks of flies respond to these
changes. They can also expose flies to different periods of bright and
dark light to modulate or disrupt their circadian clocks by irradiating
specific rays of light to further explore adaptation mechanisms.
Zebrafish is also a preferred model for studying the biological clock
due to its unique characteristics, which includes the ease of producing
a large volume of offspring, a short reproductive cycle, and transparent
embryos. Research on the animal’s biological clock is based on
behavioral observations such as diet and movement.
To support research on the effects of light on cells and animals, there
are already light cell incubators, light animal houses, and other
equipment that researchers can utilize. People can even wear light
equipment to better observe and analyze the influence of light on
organisms.
Applications of controllable light
Modern light has many applications in human health, mainly divided into
daily life and medicine.
People often use various lighting appliances and equipment in their
daily life, such as home lighting, solar panels, computer screens, smart
phones, cameras, LED TVS, etc. In addition, modern lighting technology
is also used in indoor lighting, energy-saving lamps, neon lights,
fluorescent lamps and so on. Lighting is an important part of people’s
lives, and with the development of communication as well as control
technology, the concept of intelligent lighting has been proposed. The
appearance of intelligent lighting improves the comfort of people’s life
and is beneficial to human health.
In the field of medicine, illumination is widely used in clinical
diagnosis and treatment. For example, doctors often use light scopes,
microscopes, fluorescence detectors, and so on for examination and
diagnosis. In addition, modern optical technology is also used in vision
correction, eye surgery, skin disease treatment, cancer treatment, etc.
The application of light in disease treatment is summarized in Table 3
and figure 3. The application of light in the treatment of diseases
requires careful consideration when selecting appropriate light sources.
Every color of light has different curative effects, making it crucial
to select the corresponding light source depending on the type of
disease being treated. The intensity and timing of light should remain
controlled. Overexposure to light may potentially harm the skin and
eyes, so suitable regulation is necessary. To prevent bacterial
infection in the light therapy area, the treatment region should remain
clean. It is also important to take all necessary protective measures
during treatment. It is best to follow the advice and instructions of
your doctor when it comes to light therapy for specific diseases. This
approach helps to ensure maximum therapeutic effectiveness while
minimizing the possibility of any adverse side effects.
Conclusions and Prospects
Improve people’s understanding of light and its impact on
health: With advancements in medical science and technology and the
widespread dissemination of information, people are becoming more
knowledgeable about health and are increasingly focusing on prevention
and self-care. Consequently, the connection between light and well-being
is gaining more widespread recognition and acceptance.
LED technology: LEDs are a novel lighting technology that is
continually gaining popularity due to its high light efficiency,
adjustable color temperature, and rapid response times. Moving forward,
LEDs may adapt even better to the sleep cycle and the rhythms of vital
organs such as the liver, lungs, and brain. Additionally, they could
help overcome issues related to light pollution and reduce the strain on
the eyes and brain. In the field of biological research, LED light
sources are increasingly prevalent in the growth of plants, animals, or
cell incubators. In medicine, phototherapy technology applies low-energy
red and near-infrared light to improve chronic conditions such as
cardiovascular and cerebrovascular diseases.
Precise health lighting system: Involves adjusting light
intensity and color, controlling direction and distribution, as well as
selecting and adjusting spectral optical parameters to better meet
people’s physiological and psychological needs. Precise light control
can help synchronize with the rhythm of the human biological clock,
minimizing the impact of lighting on the body and promoting overall
health.
Artificial sun: It is a device that heats hydrogen isotopes,
deuterium and tritium, in a magnetic field, causing them to fuse and
produce plasma and energy similar to that of the sun. In the long run,
this technology has the potential to replace existing energy sources,
freeing us from dependence on limited resources and producing minimal
radioactive waste. Moreover, it could help treat chronic diseases such
as cancer by delivering stronger radioactive energy to destroy tumour
cells. Artificial sun technology may revolutionize the way we live our
lives.
Pulsed light technology: Characterized by its instantaneous
high-intensity light. It is commonly used in the beauty industry for
laser hair removal, acne removal, freckle removal, and other beauty
treatments. Moreover, in the future, it holds the potential for use in
medical fields such as cancer treatment, eye surgery, and skin disease
treatment.[167]
Non-invasive rapid diagnosis and detection: Using light has a
wide range of applications in various fields such as skin, eyes, oral
cavity, and orthopedics. Optical technology in the medical field is
highly valued and rigorously developed due to its advantages of being
non-invasive, with low damage, safety, and cost-effectiveness.
Wearable clothing and equipment: Innovations are constantly
evolving, with UV protection clothing and clothes that glow in the dark
already introduced. Looking to the future, luminous clothing is expected
to emerge to aid in the treatment of specific diseases.
Medical equipment: Lasers are primarily used to treat skin and
oral ailments in existing devices. However, the emergence of more
affordable LED lights is expected to transform this industry.
Daily lighting improvement: Improvements in daily lighting are
also on the horizon, with more affordable LED lights set to become
widely available. The next big trend in this area is ”healthy lighting,”
which utilizes harmonic light that is adjusted based on human rest
patterns. This innovative lighting method is designed to help people
concentrate and promote better overall health without relying on
traditional lighting methods like sunbathing or UV radiation exposure.
Optogenetics: Optogenetics is a technique that combines genetic
and optical methods to selectively activate or deactivate specific
events in living tissue cells.[168, 169] Optogenetics technology is
not widely used in humans, mainly because its safety and effectiveness
have not been fully established. Although some experiments have shown
that optogenetic techniques are effective in mice and other animal
models, the long-term effects and safety in humans still need to be
further studied and validated. In addition, optogenetics technology also
needs to solve how to precisely control the release of optical signals
and the range of treatment.
Photocuring technology: In photocuring, UV or visible light, or
electron beams, are used to polymerize the coating’s polymer, resulting
in the formation of a hardened and solidified substance. This process is
environmentally friendly and has several advantages, including fast
speed, low energy consumption, simple operation, and low cost. It’s
important to note that photocuring technology is not directly related to
light’s effects on the human body. In recent years, there has been a
significant advancement in photocuring technology, and it has found
extensive applications in the field of human health. This technology has
been extensively used in coating, printing, adhesives, optical fiber
communication, 3D printing, and various other fields.[170] In
particular, it has become increasingly popular in teeth light curing for
whitening purposes and also for sealing holes and grooves in children’s
teeth.[171]
In the future, precision therapy using light will require the use of
advanced technologies such as medical image processing and artificial
intelligence to develop personalized treatment plans based on various
factors, including the patient’s condition, disease stage, and
individual differences. Monitoring tools like spectrometers, electron
microscopy, doppler ultrasound, and other sensors will be used to track
the therapeutic effect and adjust the treatment plan accordingly,
achieving the goal of precise treatment. Concurrently, basic research
will continue to explore and develop new phototherapy techniques to
enhance treatment accuracy and efficacy. These innovative technologies
hold promise for more precise, low-dose, and non-invasive treatment
approaches. As we continue to gain a deeper understanding of the effects
of light on our bodies and minds, our relationship with it will
inevitably evolve. By optimizing our exposure to various types of light
and using phototherapy, we can enhance our well-being and ultimately
improve our quality of life.