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.