3. How does light affect living organisms?
- 3.1 What is light and how is it absorbed and measured?
- 3.2 How can light affect biological systems?
3.1 What is light and how is it absorbed and measured?
The SCENIHR opinion states:
3.4. First principles and biology
3.4.1. Optical radiation
Wavelengths of visible EM radiation range from 400 to 780 nm (1 nm = 10-9 m), spanning the visible range from violet to red light (see CEI/IEC 2006/62471, Directive 2006/25/EC2). In article 2a of Directive 2006/25/EC the visible range is positioned more broadly between 380 and 780 nm. Light can be manipulated by a variety of optical devices or elements; most characteristically a beam of light can be focused or diverged by optical lenses made of crystal (quartz) or glass, as in binoculars, telescopes and cameras. Optical radiation encompasses light but also includes EM radiation of wavelengths well beyond the visible range: ultraviolet (UV) radiation is below 400 nm down to 100 nm and infrared (IR) radiation is above 780 nm up to 1 mm. UV and IR radiation can also be manipulated by optical devices and elements such as optical lenses (sometimes optical radiation is referred to as “light”, and one then speaks of “UV light” and “IR light”, next to “visible light”; here the latter is considered a tautology and the former two are consequently oxy).
The UV band is sub-divided in three wavelength regions (CIE 2006/62471):
- UVA from 400–315 nm
- UVB from 315–280 nm
- UVC from 280–100 nm
The IR-band is similarly sub-divided in three wavelength regions (CIE 2006/62471):
- IRA from 0.78 to 1.4 μm (μm = 10-6 m)
- IRB from 1.4 to 3.0 μm
- IRC from 3.0 μm to 1mm
Formally, this leaves the stricter range of 400-780 nm as the wavelength range of visible radiation, light.
Although the sun emits optical radiation over the full wavelength range, the earth’s atmosphere blocks UVC and part of the UVB irradiation below 290-295 nm (mainly by oxygen and stratospheric ozone) and IRC of wavelengths over 30 μm (by water vapour). Interestingly, the sun’s spectrum peaks over the visible range. Although UV is classified as non-ionizing radiation, it can cause chemical reactions, and causes many substances to fluoresce. Most people are aware of the effects of UV irradiation through the painful condition of sunburn, but UV irradiation has many other effects, both beneficial and damaging, to human health.
3.4.2. Radiant energy absorption
For optical radiation to have an effect on matter the radiation needs to be absorbed, i.e. the radiant energy needs to be transferred to the material in which the effect is to occur. Two main mechanisms can be distinguished through which the absorbed radiant energy can take effect:
a) Heat: radiant energy is converted into molecular motion (kinetic energy) such as vibration, rotation and translation. Thus the temperature is increased (photothermal effect). Here, the radiant energy (measured in Joules, J) absorbed per unit time (s) in a certain volume determines the rise in temperature, i.e. the absorbed radiant power (J/s = Watt, W) per unit volume (m3) or the (specific) absorption rate (W/m3) is the determining factor (next to how fast the absorbing volume is cooled by heat exchange with its environment).
b) Photochemistry: radiant energy can cause excitation of atoms or molecules by moving the outermost (valence) electrons to higher orbital energy levels. This energy can subsequently be utilized in (photo-)chemical reactions, yielding “photoproducts”. The radiation needs to be within a certain wavelength range (the “absorption band”) for the excitation to take place as the radiant energy is absorbed in discrete quanta, “photons”, which must match the energy required for the excitation. The (part of the) molecule that absorbs the radiation is dubbed the chromophore. Not every excited molecule will cause a chemical reaction: the energy may be lost through fluorescence (emission of radiation of longer wavelengths) or dissipated as heat. This implies that only a certain fraction of the absorbed radiant energy is channelled into the (photo-) chemical reaction: this is represented by the quantum efficiency (the number of photoproducts formed per photon absorbed; a ratio usually <1). The absorbing molecule is not necessarily the molecule that is chemically altered; the energy can be transferred to another molecule, which may then become chemically reactive (e.g. radicals and reactive oxygen species may thus be formed). In general, the total radiant energy (radiant power times exposure time in W x s=J) absorbed by the proper chromophores determines to what extent the photochemical reaction has evolved, i.e. the amount of photoproduct formed.
Of the three types of optical radiation, UV radiation is photochemically most active (the photons carry the highest energy), and it is absorbed by certain common chromophores in organic molecules (e.g. C=O, C=S and aromatic rings; the latter are abundantly present in DNA (Figure 3
)). Clearly, light is also photochemically active in the eye: visual perception starts with the photo-isomerisation of opsin proteins (in G-protein coupled receptors which trigger the neural signalling). In the skin there are also other chromophores that absorb light. For example, heme-ring structures are present in enzymes, such as cytochrome-c oxidase in the mitochondria. This enzyme is even sensitive to IRA radiation of wavelengths around 820 nm (Karu et al. 2004) by excitation of a copper atom. However, by and large, IR radiation is not capable of moving valence electrons to higher energy levels (the energy transferred per photon is too low for excitation of valence electrons) and thus initiate photochemical reactions. Most IR effects are heat-mediated.
The light interacts with eye tissues and molecules through different mechanisms. Some of the eye tissues or pigments can absorb light and thus reduce retinal exposure. In other parts of the eye or pigment structures, the light can induce oxidative stress damage defined as photochemical and photodynamic effects.
Figures 4 a-d below show the penetration/absorption of radiation by the eye for different age groups (all figures adapted from Sliney 2002).
Figure 4b. Specificity of optical radiation interaction with the eye of children below 9 years of age (adapted from Sliney 2002)
Figure 4c. Optical radiation interaction with the young human eye (10 years old up to young adulthood) (adapted from Sliney 2002)
Figure 5. Light penetration in the skin
(attenuation down to 1% occurs for light wavelengths of 250-280 nm at around 40 μm depth; for 300 nm at 100 μm; for 360 nm at 190 μm; for 400 nm at 250 μm; for 700 nm at 400 μm; for 1.2 μm at 800 μm; for 2 μm at 400 μm; for 2.5 μm at 1μ; and for 400 μm at 30 μm)
188.8.131.52. Photobiology and dosimetry
In photobiology, optical radiation usually penetrates a body through the outer surface (skin or eye), and the exposure (radiant energy per surface area in J/m2) and exposure rate or irradiance (radiant energy per surface area per unit time in J/m2s, W/m2) are the commonly used proper photobiologic metrics by which to quantify the transfer of radiant energy to the body. However, by convention, in some disciplines such as ophthalmology and dermatology the exposure is most often given as mJ/cm2. This convention is also followed in this document. The eye has the special feature of focusing the light onto the retina whereby the irradiance from the surface of the eye to the retina is increased by several orders of magnitude (up to 200,000-fold; see University of Waterloo safety office
). The irradiance at the retina over the image of a light source (either a lamp or an object reflecting light) is determined by the diameter of the pupil and the radiance of the light source. The radiance is the power transmitted into a solid angle onto the pupil per surface area of the source (in W/sr.m2). Interestingly, the distance from the light source drops out of the equation for a source with a homogeneous radiance over its surface (see Box I ) if the light is not attenuated by absorption or scattering in the air between the eye and the light source. At greater distances the pupil catches less of the light from the source, but as the image of the source becomes smaller with larger distances, more of the radiant surface is projected onto a small area on the retina. These loss and gain with distance cancel each other out, leaving the irradiance in the image area on the retina unchanged. It should be noted that a very bright source will cause immediate aversion and thus will not be focused on for any substantial length of time. The skin remits by back scatter much of the incoming visible and IRA radiation but absorbs most of the UV and IRB and IRC radiation. The penetration of the optical radiation into the tissue (skin or eye) determines to what depth effects or damage can occur, but also over which volume of tissue the absorbed radiant energy is spread; Figures 4 (a-d) and 5 illustrate the penetration of UV, visible and IR radiation (only depicted for skin) into the eye and the skin, respectively. From these figures it is clear that visible and IRA radiation penetrate deepest into the skin (10- fold reduction at 0.1-0.4 mm depth) and eye (onto the retina), whereas UVA and UVB radiation reach the lens in the eye. Short wavelength UVC and long wavelength IRB and IRC penetrate the skin only very shallowly and do not reach the lens in the eye. The superficial absorption of broad-band IRB and IRC radiation implies that most of the radiant energy is absorbed in a very thin layer which can consequently be heated efficiently.
In the IRB and IRC region of the spectrum, the ocular media is opaque as a result of the strong absorption by their constituent water. Beyond a wavelength of 1.9 μm the cornea becomes the only absorber. Direct exposure to high levels of IRC (>1W/cm2) may induce corneal lesions, particularly of the epithelium. The human cornea transmits radiant energy only at 295 nm and above (and thus not in the UVC range). Indeed, all UVC (100-280 nm) radiations are absorbed by the human cornea which absorbs radiation. It absorbs light very efficiently, over 90%, between 300- 320 nm (UVB range), about 30-40% between 320-360 nm (UVA range) and almost 100% above 800 nm (i.e. IRA, IRB and IRC ranges) (Sliney 2002). Almost no absorption occurs in the spectrum of visible radiation.
However, the part of UVA that is transmitted from the cornea is absorbed in the aqueous humour, the lens and even in the vitreous. Indeed, about 45-50% of the UVA is absorbed by the lens. Part of the UVA transmitted by the lens is then absorbed by the vitreous, so that only 1-2% of the UVA reaches the retina. In young children (at about or just below 9 years of age, where the limit is approximate since no study has clearly defined it), a window exists that allows transmission of about 2-5% of UV at 320 nm to the retina (Gaillard et al. 2000). At older ages no UV at this wavelength reaches the retina (Dillon et al. 2004). The other main difference in young children compared to adults and older children is the transmission of blue light by the lens. Around 15% of 400 nm and about 65% of 460-480 nm wavelengths reach the retina in children less than 9 years of age, compared to 60% at 460-480 nm at 10 years. In the age group of 60-70 years, only ca. 1% at 400 nm and 40% at 460-480 nm reaches the retina. This difference is explained by the fact that the colour of the lens becomes more and more yellow with increasing age (Gaillard et al. 2000). It is important to note that even without any clinically detectable cataract, changes in transmission are occurring in the lens (Ham et al. 1978). The age at which transmission of blue light decreases may be variable due to genetic, nutritional and exposure factors. Therefore the percentages given in these schemes are approximate and intended to give a range of ocular media transmission as a function of age and spectrum.
Although some photochemically mediated biological effects may depend on the total amount of photoproducts irrespective of the spatial distribution, others may depend on the density of photoproducts, i.e. the amount per surface area or volume. If the photoproducts are removed from the tissue (dead cells in days) or repaired (DNA damage in hours to days), the effect in the tissue will evidently depend on how quickly the photoproducts are generated. After absorbing light, visual pigments (opsins) take minutes to get regenerated (Sandberg et al. 1999). Following exposure of the eye to very intense illumination, a greatly elevated visual threshold is experienced, which requires tens of minutes to return completely back to normal. The slowness of this phenomenon of “dark adaptation” has been studied for many decades, yet is still not fully understood. Upon photon excitation, rhodopsin undergoes photoactivation and bleaches to opsin and all-trans-retinal. To regenerate rhodopsin and maintain normal visual sensitivity, the all-trans isomer must be metabolized and reisomerized to produce the chromophore 11-cis-retinal. This constitutes the visual cycle, which involves the retinal pigment epithelium, where all-trans retinoid is isomerized to 11-cis-retinol. The time- course of human dark adaptation and pigment regeneration is determined by the local concentration of 11-cis retinal. After intense light exposure, the recovery is limited by the rate at which 11-cis retinal is delivered to opsin in the bleached rod outer segments.
Radiations of different wavelengths will generally differ in the efficiency by which they trigger a chemical reaction or evoke a biological response; i.e. the wavelength at which a smaller exposure is required for a certain (level of) response is more efficient (such differences largely depend on the absorption spectrum of the relevant chromophore and the transmission of the radiation through the medium or tissue to the chromophore). The wavelength dependence of this efficiency is dubbed an “action spectrum” (a wavelength by wavelength plot of the inverse of the exposure needed for a certain response). Such an action spectrum can be used for spectral weighting of the exposure to a source to ascertain the biologically effective exposure or photobiologic dose (for details in formulae see Box I).
The European Standard EN 62471 recommends evaluating the Photobiological Risk Group for General Lighting Systems (GLS) at a distance where the horizontal illuminance is 500 lx. However, the same standard underlines that for all other lamp types this evaluation has to be carried out at 200 mm. The two recommendations are consistent with two distinct risks: the first (500 lx) corresponds to the situation for a worker in a well- illuminated environment without direct view of the light source; the second (200 mm) is more appropriate for evaluating the risk of a person looking directly in the direction of the light source. Following this reasoning, it is recommended to evaluate the risk class based on the potential use of the light source by the end-user. For example, light sources within ceiling fixtures or indirect lighting can be characterized at 500 lx level, whereas task lights, downlights, etc. that can be in the line of sight should be evaluated at 200mm.
Source & ©: , Health effects of artificial light, 19 March 2012,
3.2 How can light affect biological systems?
The SCENIHR opinion states:
3.4.3. Biological effects
Overexposure can cause dysfunction or outright destruction of tissue, either through heating or photochemical reactions. As implied by the term “overexposure”, a certain threshold of tolerable levels of exposure or irradiance is surpassed: the irradiance can become too high and cause thermal damage or the accumulated exposure carries a photochemical reaction to a toxic level. It should be stressed that this does not imply that there is no biological effect below the threshold level, but the damage is minor and tolerable (non-destructive) and/or the absorbed radiant energy causes a functional biological response (receptive absorption). Below we present biological effects from “receptive absorption” or by “destructive or toxic overexposure”.
184.108.40.206. Photothermal effects
Absorption of optical radiation by the skin will cause heating which can raise the temperature. The skin can sense temperature differences smaller than 0.1°C on the face, especially on the lips (Jones 2009, Stevens and Choo 1998). The skin is innervated by axons (nerve endings from neurons residing in the spine) which carry transient receptor potential (TRP) ion channels that are sensitive to temperature changes in their cell membranes. Some axons carry TRP channels that are activated below certain temperatures, sensing cold, whereas others are activated above certain temperatures thus giving a hot sensation (some of these TRPs are also present on the tongue and respond to menthol, a “cool” sensation, and capsaicin in pepper, a “hot” sensation (Denda et al. 2010). Very recently, transient receptor potential vallinoid (TRPV) channels have also been found in human cornea cells (Mergler et al. 2010). They may be involved not only in thermo-sensation, but also in the regulation of cell proliferation. In the retina, TRPV channels have been identified that are more sensitive to pressure than temperature (Sappington et al. 2009).
Proteins can become denatured (loss of tertiary structure) at high temperatures and, cells and tissue irreversibly damaged in 15 to 60 minutes at 45°C (Kampinga et al. 1995) and in a matter of seconds at 60-70°C (Biris et al. 2009, Priebe et al. 1975). Pain and retraction reflexes evidently serve to limit the damage. Blisters may develop first due to loss of adherence between skin layers. Limited superficial thermal wounds, as from cosmetic or therapeutic skin ablation by laser treatment, can be restored from deeper and neighbouring layers of skin, but extensive third degree deep burns need special medical care and skin transplants. The immune system will respond to thermal damage by an inflammatory reaction in the skin. Regarding thermal damage to the eye, only pulsed lamps are of concern. If the rate of energy deposition is faster than the rate of thermal diffusion (thermal confinement), then the temperature of the exposed tissue rises. If a critical temperature is reached (typically about 10°C above basal temperature), then thermal damage occurs. Thermal injury is caused mainly by absorption of light wavelengths >450 nm by the retinal pigment epithelium; the effects are usually immediate. Thermal burn is rare unless the light source is pulsed or in near contact with the eye. Thermal damage usually does not occur with domestic lights but can be induced by pulsed lamps and lasers. In such cases, retinal damage is primarily induced via thermal mechanisms for exposures shorter than 5 seconds. During longer exposure times both thermal and photochemical damage takes place.
Adverse effects Threshold levels for photokeratitis: 3-4 mJ/cm2 (270 nm), 10 mJ/cm2 (300 nm). Threshold levels for cataracts: 600 mJ/ cm2 (300 nm), 2 J/cm2/ cm2 (>315 nm), 4 W/cm2 for IR. Retinal thermal damages (burns): 1-1,000 W/cm2 depending on spot size. Figure 6 Adverse effects of light on eye tissues as a function of wavelength (adapted from Sliney 2001, Sliney et al. 2005a)
220.127.116.11. Photochemical effects
A. Physiological responses
A1. In the eye
The iris responds to light by constriction, the pupillary reflex, thus reducing light entry into the eye. This mechanism is extremely important and efficient for protecting the retina against light damage. Pupillary constriction is highly dependent on the wavelength. Lucas et al. (2001) showed that the pupillary light reflex in mice was driven by a non- rod, non-cone photoreceptive system using a photopigment with peak sensitivity around 479 nm (melanopsin). The work of Hattar et al. (2003) recognized the melanopsin- associated photoreceptive system as being responsible for conveying photic information for accessory visual functions such as pupillary light reflex and circadian photo- entrainment. In humans, light pupillary constriction is achieved at a peak sensitivity of 482 nm and the sustained, post-stimulus pupil constriction is mediated predominantly by the melanopsin-driven, intrinsic photoresponse and not by sustained rod activity resulting from bleached rhodopsin as had previously been suggested. Light pupillary constriction is observed at 5 cd/m2 at 482 nm in humans and primates (Gamlin et al. 2007). The retina The peak of absorption of the retina is between 400 and 600 nm and its transmission is between 400 and 1,200 nm. Rods are present across the retina except for the very central region (the foveola), and provide scotopic (night) vision. Their sensitivity is 10-6- 1 cd/m2, with comparatively low resolution and high sensitivity, but lacking colour information. Their absorption peak is at 498 nm (blue), but in vivo, if the lens absorption and macular pigments are taken into account, the effective maximum sensitivity of the rod integrated in the eye is shifted to 507 nm. Cones are responsible for daylight (photopic) vision. Their sensitivity varies in a wide luminance range, from 10-3-108 cd/m2. Maximal absorbance for blue cones is around 450 nm, 530 nm for green cones and 580 nm for red cones.
The visual pigment in the rod is rhodopsin, which consists of opsin and the vitamin A aldehyde 11-cis-retinal. Phototransduction is triggered by the photic conversion of 11- cis-retinal to all-trans-retinal in the rhodopsin molecule. The activation of rhodopsin starts a cascade of events that leads to the closure of sodium channels, hyperpolarization of the photoreceptor membrane, and a decrease in the concentration of intracellular calcium (Pepe 1999). The phototransduction system can be modulated by several proteins (such as S-modulin [recoverin], S-antigen [arrestin], guanylate cyclase- activating protein, phosducin, and calmodulin) in a calcium-dependent manner, inducing light and dark adaptation. Rhodopsin is regenerated in the retinal pigment epithelial (RPE) cells through the visual cycle of retinoid metabolism (Bok 1990, Saari et al. 1994).
A2. In the skin In the skin (solar) UV radiation drives the formation of pre-vitamin D3 from pro-vitamin D3 (7-dehydrocholesterol, a precursor of cholesterol). At skin temperature the pre- vitamin D3 isomerizes to vitamin D. Prolonged UV exposure however does not continue to raise vitamin D3 levels. Instead, surplus vitamin D3 is converted into inert substances and further UV exposure increases the risk of undesirable effects such as burning (Webb et al. 1989), see below section 18.104.22.168 (Figure 8
). Regular and moderate sun exposure in summer appears optimal for adequate vitamin D3 production.
B. Damage B1. In the eye The cornea Exposure of the cornea to UVA and UVB usually induces reversible lesions of the corneal epithelium. UVC can induce lesions of the corneal stroma and the Bowman membrane leading to corneal opacity and potentially to corneal neovascularization. IR usually only causes irritation but may, at high energy levels (>3 mJ/cm2), also cause deep stromal lesions and even perforations. Protection from IR and UV components of the sunlight is therefore recommended in certain instances (Sliney 2001). Upon prolonged exposure to UV (sunlight), climatic droplet keratopathy and cortical cataracts (opacification of the cortex of the lens and not the nucleus) can occur. On the conjunctiva, pterygium and conjunctival neoplasms can be observed. Ocular melanoma (mostly uveal melanoma) might also be induced by UV overexposure. Evidence for an association between ocular melanoma and sun exposure comes from Australia. A national case-control study of ocular melanoma cases diagnosed between 1996 and mid-1998 demonstrated an increase in risk of the cancer with increasing quartile of sun exposure prior to age 40 (relative risk (RR) in the highest quartile 1.8; 95% CI 1.1–2.8), after control for phenotypic susceptibility factors (Vajdic et al. 2002). The subclinical photokeratitis level normalized to the UV-hazard action spectrum peak at 270 nm wavelength is approximately 4 mJ/cm2 (as defined by ACGIH and ICNIRP, and stated in EU Directive 2006/25/EC). The radiant exposure at 300 nm that would be equivalent to the corneal exposure of 4 mJ/cm2 at 270 nm is 10 mJ/cm2. Between 315- 400 nm, the exposure guideline limit is 1 J/cm2 for t <1000 s. The lens The lens absorbs near UV and far infrared light (<400 and >800nm) (Boettner and Wolter 1962). It is known that UV light induces cataracts (Hockwin et al. 1999, Sasaki et al. 1999) with a damage threshold of 600 mJ/cm2 at 350 nm.
A corresponding value for 310 nm is 750 mJ/cm2. Blue light may induce photodynamic damage in lenses which have accumulated photosensitive debris or drugs. Other compounds that accumulate in the aging lens may act as antioxidants (Balasubramanian 2000). Infrared may also cause cataracts (Roh and Weiter 1994). Cortical cataracts have been associated with UV exposure. Furthermore, it seems that exposure to UV at younger ages also predisposes individuals to nuclear cataracts later in life (Neale et al. 2003).
Whether cumulative UV exposure from artificial lighting, added to the natural light exposure, might increase the incidence of cataract at younger ages was never investigated. The absorption spectrum of the lens changes with age. In young children, more than 80% of blue light is transmitted to the retina. At around 25 years of age, only 20% of the light between 300 and 400 nm and 50% of wavelengths between 400 and 500 nm is transmitted. With increasing age, the yellow filters of the lens increase and absorb most of the blue light. The peak of absorption of the lens is around 365 nm in young adults and around 400 nm at 60 years. This natural retinal protection of the lens, increasing with age, tends to be replaced in the case of cataract surgery by yellow intraocular lenses (Margrain et al. 2004).
Light (particularly short wavelengths) can interact with photoreceptor associated opsins and retinoids and cause damage via the overproduction of reactive oxygen species (ROS) (Boulton et al. 2001), but such damage can also arise outside the photoreceptors. In the retina, photochemical damage through oxidative stress takes place when the incident radiation has a wavelength in the high energy portion of the visible spectrum. The retina, which contains a large concentration of cell membranes, is particularly sensitive to oxidative stress because lipid peroxidation breaks down membranous structures. The photochemical damage spreads from the absorbing molecule to other molecules in an uncontrolled molecular chain reaction. There are two classes of photo- damage (see also overview in Table 2 below):
- Class I damage has an action spectrum that is identical to the absorption spectrum of the visual pigment, and it appears after exposure (of several hours to weeks) to irradiances below 10 W/m2 of white light estimated at the retina. For comparison, an approximation calculated for this document suggests that the retinal illuminance caused by the sun shining on snow or white sand on a clear day is in the order of 30- 60 W/m2. The initial damage is mainly located in the photoreceptors, where reactive oxygen species (ROS production) can be measured upon blue light exposure in vitro (Figure 7
). However, depending on the species, it seems that both RPE and photoreceptor cells can be the primary target sites.
- Class II damage has an action spectrum that peaks at shorter wavelengths, and this type of damage occurs following exposure to high irradiances of white light, at or above 100 W/m2. The initial damage is generally confined to the retinal pigment epithelium (lipofuscin-mediated) but may then extend to the photoreceptors. In RPE cells, lipofuscin granules are converted to melanolipofuscin in aging eyes, and the lipofuscin becomes much more phototoxic and particularly sensitive to blue light with increasing age, meaning that more free radicals may be produced in the eyes of elderly people. The damage that occurs in RPE cells and subsequently in photoreceptor cells is irreversible. The damage occurrence depends on the anti- oxidant status of the retina and also on the local oxygen tension in the outer retina. The photooxidative damage taking place in the outer retina is cumulative.
Figure 7. Production of reactive oxygen species (ROS) by rod photoreceptors exposed to blue light in vitro (adapted from Yang et al. 2003)
Other pigments exist in mitochondria in all tissues but are particularly susceptible to photochemical damage in ganglion cells that receive light directly on the retinal surface. Their peak absorption is also in the blue spectrum (e.g. peak at 450 nm for flavine).
In the macula of the retina, yellow pigments located in the inner retinal layers are particularly concentrated in the fovea. The lutein and zeaxanthin pigments efficiently absorb blue light between 400 and 500 nm (Whitehead et al. 2006). Lutein protects against oxidative damage and is a scavenger for singlet oxygen (Davies and Morland 2004, Krinsky et al. 2003, Li et al. 2010, Wooten and Hammond 2002). However, humans cannot synthesize macular pigments. They are highly concentrated in the macula of children and additional amounts of macular pigment can only be achieved through nutrient intake. Nutrient supplements have been shown to increase macular pigment density in older patients and are therefore considered to reduce the risk for progression of age-related macular degeneration (AMD) (Carpentier et al. 2009, Loane et al. 2008).
RPE cells are polarized epithelial cells with long microvilli on their apical surfaces, interfacing with the outer segments of photoreceptor cells. The tight junctions between RPE cells constitute the outer blood-retinal-barrier, selectively controlling the passage of water and ions between the subretinal space and the choroids. RPE cells play a crucial role in the phagocytosis of photoreceptor outer segments and regeneration of visual pigments (Bok 1990). At their apical side, RPE cells contain intracellular melanin granules (eumelanin and pheomelanin) as well as many microperoxisomes and antioxidative enzymes, which act as protective and anti-oxidative mechanisms. Particularly, melanin absorbs the excess of photons from 300 to 700 nm. Lipofuscin is a mixture of chromophores that accumulates in the retinal pigment epithelium with age and in the case of several retinal disorders. It is a potent photosensitizer capable of inducing photodynamic effects and subsequent photochemical processes (Boulton et al. 1990, Wang et al. 2006), possibly causing permanent damage to RPE and photoreceptors (Wassel et al. 1999). The major fluorescent component of lipofuscin, A2E, has been identified (Sakai et al. 1996). A2E is formed in rod outer segments by a sequence of reactions that is initiated by the condensation of two molecules of all-trans-retinaldehyde with phosphatidylethanolamine. It has a visible absorption maximum between 430 and 440 nm, depending on the solvent, and generates light induced ROS (Parish et al. 1998, Reszka et al. 1995). Interestingly, age- induced changes in the lipofuscin composition and structure increase its photodynamic effect upon illumination, resulting in higher oxidative damage (Wu et al. 2010).
Several other native retinal chromophores including melanin (Margrain et al. 2004), protoporphyrin (Gottsch et al. 1990), all trans-retinal (Delmelle 1978, Wielgus et al. 2010) and other lipofuscin components (Gaillard et al. 1995, Reszka et al. 1995, Wassel et al. 1999) have been suggested to act as photosensitizers of damage. The maximal potential phototoxic retinal damage is expected to occur with blue light wavelengths between 430 and 460 nm.
It has been recognized that retinal mitochondria also contain photosensitizers capable of generating ROS under blue light stimulation in photoreceptors (Chen et al. 1992a, Chen et al. 1992b), RPE cells (King et al. 2004, Youn et al. 2009) and in retinal ganglion cells (Osborne et al. 2006). A recent hypothesis suggests that retinal ganglion cells, which are particularly rich in mitochondria, may suffer from light-induced damage, particularly in pathologic conditions such as glaucoma (Osborne 2010). ROS generation by retinal mitochondria is mostly stimulated by the shorter blue light wavelengths (404-420 nm). The interaction between light of different wavelengths and eye structures, and the possible consequences is presented in Table 3 below.
B2. In the skin
As pointed out earlier, UV radiation is very (photo-) chemically active on a large variety of organic molecules, most prominently on DNA. Next to direct damage to molecules like DNA, UV radiation can generate reactive oxygen species and various kinds of radicals which can then damage cell components. At low UV exposure levels the skin is perfectly capable of coping with this UV challenge through antioxidants, radical scavengers and repair mechanisms, and the exposure will have no direct noticeable effect (see de Gruijl 1997). If the exposure, and the damage, increases to levels where the functions of the cell become seriously disturbed, the cell may become apoptotic (undergoing programmed cell death). The UV radiation at higher levels has a clear toxic impact which evokes an inflammatory reaction. In the long term, sub-acute damage may cause accumulation of gene mutations in the (stem) cells of the epidermis (causing cancer) or cause loss of collagen in the dermis with a subsequent gradual loss of elasticity (“photo-aging”). Specific UV signature mutations (at sites of neighbouring pyrimidine bases in the DNA) were found in p53 tumour suppressor genes in a majority of human skin carcinomas, providing direct evidence that UV radiation had contributed to the development of these tumors (de Gruijl et al. 2001).