Photobiology is the study of the local and systemic effects of incident radiation on living organisms. Solar radiation is made up of ultraviolet, visible and infrared radiation. Ultraviolet radiation is made up of UV-C, UV-B, and UV-A. Sun exposure can lead to sunburn, tanning, vitamin D production, photoaging, and carcinogenesis. Phototherapy is the use of nonionizing radiation to treat cutaneous disease. Various types of artificial light sources are used for photo testing and phototherapy.
Key points
- •
Solar radiation is made up of ultraviolet, visible, and infrared radiation.
- •
Ultraviolet radiation is made up of UV-C, UV-B, and UV-A.
- •
Most ultraviolet radiation that reaches the earth is UV-A.
- •
Sun exposure has a wide range of biological effects, including sunburn, tanning, vitamin D production, photoaging, and carcinogenesis.
- •
Phototherapy uses properties of ultraviolet light that are useful in the treatment of certain dermatologic conditions.
Introduction
Photobiology deals with the local and systemic effects of incident radiation on living organisms. This introductory article on cutaneous photobiology focuses on the effects of ultraviolet (UV) radiation (UVR), both from its natural source (ie, the sun) and artificial sources (ie, those used in phototherapy), on skin function and diseases. Although visible light and infrared radiation also have effects on skin cells, there is more information on UVR.
Phototherapy is the use of nonionizing radiation to treat cutaneous disease. For more than a century, phototherapy has played a pivotal role in the treatment of dermatologic diseases. In 1903, Niels Finsen received the Nobel Prize in Medicine for using light to treat a cutaneous mycobacterial disease. In the middle of the 20th century, advancements in UV-B light therapy expanded treatment options for patients with psoriasis. In the 1970s, photochemotherapy (ie, using psoralen as a photosensitizer in combination with UV-A radiation [PUVA]) made its debut. PUVA became an established player in the treatment of skin diseases in the last quarter of the 20th century. More recent advances in the last few decades (ie, narrowband UV-B therapy, laser therapy, targeted phototherapy, photodynamic therapy [PDT], UV-A1) have also revolutionized photodermatology.
Introduction
Photobiology deals with the local and systemic effects of incident radiation on living organisms. This introductory article on cutaneous photobiology focuses on the effects of ultraviolet (UV) radiation (UVR), both from its natural source (ie, the sun) and artificial sources (ie, those used in phototherapy), on skin function and diseases. Although visible light and infrared radiation also have effects on skin cells, there is more information on UVR.
Phototherapy is the use of nonionizing radiation to treat cutaneous disease. For more than a century, phototherapy has played a pivotal role in the treatment of dermatologic diseases. In 1903, Niels Finsen received the Nobel Prize in Medicine for using light to treat a cutaneous mycobacterial disease. In the middle of the 20th century, advancements in UV-B light therapy expanded treatment options for patients with psoriasis. In the 1970s, photochemotherapy (ie, using psoralen as a photosensitizer in combination with UV-A radiation [PUVA]) made its debut. PUVA became an established player in the treatment of skin diseases in the last quarter of the 20th century. More recent advances in the last few decades (ie, narrowband UV-B therapy, laser therapy, targeted phototherapy, photodynamic therapy [PDT], UV-A1) have also revolutionized photodermatology.
UVR
Solar Radiation
The rays of the sun hit the earth in the form of UVR, visible, and infrared radiation. These 3 entities are components of the electromagnetic spectrum, which also includes radiowaves, microwaves, radiographs, and γ radiation ( Fig. 1 ). Solar radiation is made up of approximately 50% visible light, 40% infrared, and 9% UVR. Visible radiation is that which is perceived by the human eye. Each color of visible light represents a different wavelength range (see Fig. 1 ). UVR is the area of the electromagnetic spectrum that is considered most biologically active and therefore of greatest impact on health and disease.
UVR
UVR spans the wavelengths 100 to 400 nm and is subdivided into UV-C, UV-B, and UV-A. There are subtle differences in the subdivisions described in the literature. In this article, the subdivision most commonly chosen in photobiology is used (ie, UV-C, 200–290 nm; UV-B, 290–320 nm; and UV-A, 320–400 nm). Other ranges referenced in the literature include: UV-C at 200 to 280 nm, UV-B at 280 to 320 nm, UV-A at 320 to 400 nm, UV-C at 200 to 280 nm, UV-B at 280 to 315 nm, and UV-A at 315 to 400 nm. The stratospheric ozone prevents wavelengths shorter than approximately 290 nm from hitting the earth. Most UV radiation that reaches the earth is UV-A. Only a small percentage (approximately 5%) of UV-B is present in terrestrial sunlight. UV-C is typically filtered by the ozone layer. The amount of solar energy at a specific wavelength that can affect the earth varies with season, region, altitude, pollution, and the path that the solar radiation traverses through the ozone. The amount of UV in sunlight also varies throughout the day. Being of a longer wavelength, UV-A is present consistently from sunrise to sunset, whereas UV-B peaks around noon. Approximately 50% of UV-A exposure occurs in the shade as a result of surface reflection and its penetration to cloud cover. Windows and automotive glass do not shield against UV-A but do shield against UV-B.
For the purposes of phototherapy, UV-B has been further subdivided into broadband UV-B (290–320 nm) and narrrowband UV-B (311 nm–313 nm). UV-A radiation has been subdivided into UV-A1 (340–400 nm) and UV-A2 (320–340 nm), primarily because the biological effect of UV-A2 is closer to that of UV-B. The specific applications of these modalities are discussed in more detail in the article by Rkein and Ozog elsewhere in this issue.
Light-Skin Interactions
Light has both the properties of waves and particles known as photons. In cutaneous photobiology, it is important to understand what happens to photons when they encounter the skin surface. They can undergo reflection, scattering, or absorption. According to the Grothus-Draper law, light can have a biological effect only if it is absorbed. Once radiation is absorbed by molecules in the skin (termed chromophores), energy is transferred to produce heat or drive photochemical reactions. This process results in detectable responses at the cellular and molecular levels that could lead to a clinical outcome ( Fig. 2 ).
Reflection, scattering, and absorption
Reflection happens at the skin surface. Light reflected from the skin can be used for diagnostic purposes but does not have much of a therapeutic role. Scattering alters the direction of the light transmission through the skin. How deep a photon can go is influenced by how much it is scattered by structures in the skin. Most scattering takes place in the dermis as a result of the presence of collagen. Scattering of radiation is also wavelength dependent; shorter wavelengths scatter more, whereas longer wavelengths penetrate deeper.
The depth of light penetration is critical for phototherapy. UV-B is generally absorbed in the epidermis and upper dermis, whereas UV-A (because of its longer wavelengths) penetrates well into the dermis ( Fig. 3 ). Shorter wavelength visible light such as blue light can be used in PDT for epidermal growths (such as actinic keratoses). Red light, which is of a longer visible wavelength, can target deeper structures such as sebaceous glands and thicker lesions. Nonetheless, penetration depth is only 1 part of the equation. The light must also be of the appropriate wavelength to be absorbed by the target molecule or chromophore. Only on absorption can a photon exert a clinical effect.
Different wavelength(s) target different chromophores, which results in a variety of cutaneous effects. Chromophores can be cellular/molecular components, such as amino acids, nucleotides, lipids, and 7-dehydrocholesterol (a vitamin D precursor). They can also be porphyrins (exogenous or endogenous), tattoo pigments, or photosensitizing drugs (eg, psoralens). DNA directly absorbs UV-B and is therefore a chromophore targeted by UV-B phototherapy. In cosmetic laser treatments, endogenous chromophores targeted are mainly hemoglobin, melanin, and water. Exogenous substances (ie, aminolevulinic acid solution, which converts to protoporphyrin IX) may also be used to act as chromophores, depending on the phototherapeutic modality.
Absorption is wavelength dependent and is influenced by the physicochemical structure of the chromophore. Each chromophore has an absorption spectrum, which is the range of wavelengths that are absorbed by that molecule. For example, the absorption spectrum for melanin is 250 to 1200 nm. The absorption maximum (ie, peak) is the wavelength or wavelengths that have the highest probability of being absorbed.
Photochemical reactions
When the chromophore absorbs the photon, it changes to a transient, excited state. Energy is released as light or heat when the chromophore returns from the excited state to the ground state. This process causes the chromophore to undergo chemical changes or transfer energy to a different molecule. Sufficient amounts of energy (ie, photons) must be present for a cellular response to occur. Only absorbed light can lead to a photochemical reaction, causing cellular changes, which eventually evoke a clinical response. Fig. 4 is an example of a photochemical reaction that takes place when a chromophore, in this case a drug such as psoralen, absorbs UV-A. Action spectrum refers to the wavelengths of the radiation that are most efficient for inducing the desired effect.
Basic principles of phototherapy
To better appreciate the accompanying articles, this introduction briefly discusses the basics of phototherapy. The specifics for different types of phototherapy are discussed in other articles elsewhere in this issue.
As mentioned earlier, phototherapy is the use of nonionizing radiation to treat cutaneous disorders. Phototherapy is typically administered in a physician’s office or treatment center. For some types of phototherapy, the patient stands in a booth lined with UV bulbs; more focused light sources, such as those used in targeted phototherapy, may also be used for treatment. The initial dose is determined empirically by assessing the patient’s Fitzpatrick skin phototype (SPT), which is mainly based on history of burning versus tanning responses. The minimal erythema dose (MED) can also be used as the guide to deliver phototherapy.
MED
To more quantitatively determine the appropriate dosage of UV radiation to administer in phototherapy, the MED is used. A few dosing-related terms used in photodermatology are defined first. Irradiance (usually expressed as J/s.cm 2 or mJ/s.cm 2 ) is the intensity of the incident radiation on the patient. The irradiance of a light source or device can be measured by a radiometer. The exposure time (in seconds) is the length of time at which the patient receives UVR. The dose (in J/cm 2 or mJ/cm 2 ) is the amount of light energy that the patient receives. These 3 values are related in the equation:
MED, also known as the sunburn threshold, is a way to measure an individual’s sensitivity to UVR. The MED is the amount of UVR that produces minimal erythema: a faint pink response on the skin, which is best appreciated 16 to 24 hours after UV exposure. To determine the MED, adjacent areas of skin are exposed to increasing doses of UVR. After a specified amount of time, the exposed areas are visually graded based on their degree of erythema. The erythematous skin that was exposed to UVR for the shortest duration is the visual MED. The visual clinical evaluation of these spots is subjective and, thus, varies from 1 observer to another. Nonetheless, a study by Bodekaer and colleagues involving a few individuals did show that objectively measured skin erythema (by a skin reflectance meter) and subjectively measured skin erythema were in good agreement. To objectively calculate the MED, a chromameter can be used to measure the amount of erythema associated with each exposed area. The intensity of UVR (and thus the MED) varies depending on the UV device used, the lamp, and how far the lamp is from the skin. Previous UV exposure or tanning also affects the MED, which is why it is usually performed in relatively sun-protected areas of the skin, such as the lower back or buttock.
The MED allows treatment to safely start at a dose that is usually higher than empirical starting doses based on SPT. This strategy usually results in achieving clinical response at a quicker pace, with fewer treatment sessions. MED is frequently used for UV-B phototherapy. The minimal phototoxic dose (MPD) is used for PUVA. MPD is also defined as the lowest dose to produce erythema. The main difference is that it involves oral ingestion of 8-methoxypsoralen 1 hour before phototesting and is typically evaluated at 72 hours. However, because of the relative complexity of performing MPD, the SPT-based protocol is more commonly used to deliver PUVA therapy.
Acute and Chronic Effects of UVR
Norman Paul established the association between sun exposure and skin cancer at the start of the 20th century. It was later postulated that UV-B caused sunburn and that UV-B–induced sunburn led to skin cancer. At the time, UV-B was considered the causative wavelength for skin carcinogenesis, and all other wavelengths were regarded as safe, Thus, sun protection products focused on blocking only UV-B rays, and it was believed that it was possible to tan without burning or causing harmful effects on the skin. Products were labeled suntan lotions for this reason. The sun protection factor (SPF) was introduced by Franz Greiter in the 1960s. By the late 1960s, UV-B exposure was noted to cause aging of the skin, and a decade later, UV-A was identified as another spectrum responsible for photoaging. As a result of these findings, in the 1980s, sun protection products changed their labeling from suntan lotions to sunscreens. Later, the concept of broad-spectrum protection was adopted, leading to the development of sunscreens with both UV-A and UV-B filters.
UV Damage on a Molecular Level
DNA damage and repair
DNA is a major target of UV-B. Although DNA maximally absorbs from 245 to 290 nm, UV-C (200–290 nm) does not penetrate the atmosphere, and thus, it is UV-B (290–320 nm) that primarily targets DNA. UV-B radiation is capable of traversing the stratum corneum. Epidermal DNA in keratinocytes and Langerhans cells directly absorbs UV-B, which is more cytotoxic and mutagenic than UV-A. UV-B causes most cyclobutane pyrimidine dimers (CPDs) and pyrimidone (6-4) pyrimidone photoproducts. These photoproducts are considered the signature lesions of UVR-induced DNA damage. The 5-6 double-bond of pyrimidine (thymine or cytosine) bases is the most efficient area of DNA that absorbs UVR. A photon is absorbed by one of the pyrimidines that form a cyclobutane ring between the 2 adjacent pyrimidines. This ring is formed at the 5 and 6 positions, which results in a CPD. CPD is the most common product when DNA damage from UVR occurs. If a bond is formed at the 6-4 linkage, it is instead referred to as a pyrimidine-pyrimidone photoproduct. Both of these photoproducts are structurally damaging. They distort the DNA helix, which halts RNA polymerase and inhibits gene expression.
UV-A, which comprises about 95% of terrestrial solar radiation, also inflicts damage in cellular DNA, despite DNA having minimal absorption within the wavelength range of UV-A. The mechanisms are believed to be indirect and involve induction of oxidative stress. DNA damage can also be caused by oxidation, most frequently at the 8 position of guanine. Oxidation by UVR results in formation of 8-oxo-guanine (8oG); thymine glycol is another oxidized base from UVR. UV-A results in more oxidative damage than does UV-B. However, UV-A has also been shown to produce more CPD than 8oG. Thus, CPD is still the most common product of DNA damage from UVR. The chromophores responsible for UV-A effects have not been defined and may be nonspecific, but presumably include proteins, lipids, and other cellular components.
DNA damage can influence DNA repair and gene expression. This situation can result in inhibition of antiinflammatory cytokines and, conversely, increased production of immunosuppressive cytokines. It can also lead to the production of collagen-degrading proteins (eg, matrix metalloproteinases). Multiple proteins and enzymes are recruited to facilitate DNA repair. Nucleotide excision repair is used to repair bulky products such as CPD. Base excision repair is used to repair modified bases such as 8oG. Other methods are also in place for DNA repair. If these methods fail, cell apoptosis or DNA mutations are the result.
During DNA repair or replication, errors can occur, and incorrect bases can be inserted. Erroneous additions, deletions, or rearrangements can occur, but most of these mutations are not catastrophic, because the genetic code is redundant and large portions of DNA are not used. However, if mutations occur at oncogenes or tumor suppressor genes, tumorigenesis may be favored. For instance, mutations of the tumor suppressor gene, p53, are found in many UV-induced skin cancers, such as squamous cell carcinomas.
Perhaps the best example that shows the importance of DNA repair after UVR damage is seen in the genetic disorder known as xeroderma pigmentosum (XP). This is an autosomal-recessive condition characterized by deficient repair of UV-induced photoproducts. The capacity to undergo DNA repair in patients with XP is decreased by up to 50%. However, their risk of carcinogenesis from UVR is increased by a factor of 1000. Patients with this disorder develop skin cancers in the first 2 decades of life, in addition to premature photoaging.
UVR-induced apoptosis
After UVR exposure, sunburn cells, or apoptotic keratinocytes, can be observed histologically. Sunburn cells can be seen as early as half an hour after UVR. This is a protective mechanism of the body to get rid of cells that may be at risk for malignant transformation. Keratinocytes are more vulnerable to UVR than are melanocytes. This vulnerability is because keratinocytes cycle more often than melanocytes. Cells are more vulnerable to undergo apoptosis when they are undergoing DNA synthesis. UV-B can lead to G1 and G2 phase cell cycle arrest. Hence, the cell cycle can be stopped before DNA replication (G1/S checkpoint) or chromosome segregation (G2/M checkpoint). If the keratinocyte is severely damaged, it is likely to be destroyed by apoptosis, whereas a melanocyte may be able to survive.
Apoptosis is a finely regulated process, with numerous checks and balances. There are antiapoptotic and proapoptotic pathways. At least 3 mechanisms are known to activate the pathways leading to apoptosis: DNA damage, membrane receptor clustering, and formation of reactive oxygen species (ROS). Apoptosis causes morphologic changes in the cell, such as cell shrinkage and membrane blebbing, with chromatin condensation and DNA fragmentation. This process leads to a cell with a pycnotic nucleus (the so-called sunburn cell) and to apoptotic bodies of membrane enclosed fragmented DNA. These apoptotic bodies undergo phagocytosis by macrophages. This process is believed to occur in specific keratinocytes, sparing the surrounding tissues.
Role of lipids
The combination of molecular oxygen plus UVR results in ROS, which can damage stratum corneum free lipids and the membranes of living cells. ROS can oxidize lipids in 1 of 2 ways: directly, by oxidizing the double bonds of the lipid, or indirectly, via a chain reaction of oxidized lipids. The processing of the damaged lipid membranes in living cells is by enzymatic and nonenzymatic reactions, which can result in the expression of stress response genes or the production of prostaglandins, which mediate inflammatory reactions.
Role of proteins
UV effects on proteins are not as severe as those on DNA and lipids. This situation may be because the skin has several proteins, which are destroyed and remanufactured constantly. Nonetheless, protein components of the skin can be oxidized by ROS. ROS breakdown collagen and elastin fibers, leading to reduced dermal structural support and volume, a major factor in the wrinkling of the epidermis. UVR can also cross-link collagen, elastin, and other proteins in the dermis, resulting in destruction of these proteins, which leads to the clinical effect of photoaging.
Some proteins are cell surface receptors, and absorption of UVR may result in receptor clustering and other changes. This situation leads to the production of extracellular signals, resulting in cell activation.
UV Damage on a Clinical Level
Sun exposure: acute and chronic effects
Sunburn and tanning
A sunburn is an acute inflammatory response to UV exposure, which causes vasodilation of dermal blood vessels. UV-B is the main culprit, and UV-B photons are about 1000-fold more efficient than longer wavelength UV-A at inducing erythema.
An individual’s inherent tendency to either burn or tan when exposed to UVR underlies the concept of SPT, or Fitzpatrick skin type, which is divided into 6 categories. Individuals with darker skin and higher Fitzpatrick SPT usually burn less and tan more, whereas Fitzpatrick SPT I individuals always burn and never tan ( Table 1 ).
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
