By Professor John Marshall
The penetration of optical radiation deep within the eye is a paradox, as light is an essential component for vision but it may also be a biohazard. Short wavelength blue-violet light is potentially harmful, while longer wavelength blue-turquoise is essential for healthy living. Professor John Marshall explains the pathogenic power of light but also its fundamental requirement to circadian rhythms. In the human eye, evolutionary development of both mechanisms has been integrated to facilitate separation of health and hazard.
The eye is the only organ in the body that has evolved to allow radiation to penetrate deep within it. In this process, however, the various ocular media, cornea, aqueous, lens and vitreous act as progressive wavelength selective filters. Ultraviolet B (280-315 nm)1 radiation is absorbed almost exclusively in the cornea while ultraviolet A (315-400 nm)1 may be attenuated by the cornea, with almost all of the remaining radiation of this wavelength being absorbed in the lens2-4 and only a very small amount passing to the retina (Figure 1). However, optical radiation between 400 and 1400nm, made up of visible radiation or light (400-800 nm)1 and infrared A (800-1400 nm),1 not only passes through the various optical media to fall upon the retina but also undergoes a concentration in irradiance of up to a hundred times between the cornea and the retina as a result of the refractive power, of the cornea and to a lesser extent the lens. It is this refractive property that concentrates the incident energy and converts for example, the rays of the summer sun from a pleasant warmth on the skin to a potential hazard to the eye if viewed directly. This penetration of optical radiation is the first paradox; radiation is a biohazard5-14 but light is essential in the process we know as vision.
Renewal Processes of Cells
In all biological systems, cells under stress are normally replaced periodically in order to combat environmental attrition. For example the cells of the skin are replaced by a never-ending cycle whereby new cells progressively move towards the surface of the body and are then shed, usually within five days of creation. This process ensures that our skin is able to cope with the problems of both friction, induced by touching things, and the effects of optical radiation. A similar process is found in the lining of the gut whereby renewal of cells overcomes the problem of focal trauma caused by the passage of food and the toxic chemical environment required for digestion. These processes make the concept of ageing in biological entities extremely difficult to define as the cells of those parts of our body which are constantly dividing may be a few days or weeks old, while those in other parts of the body, which don’t divide, may have been created shortly after conception or sometime during developmental in the womb.
Toxic Blend of Oxygen and Light
Here is a second paradox. The retina may be considered as part of the brain as it develops early from the neural tube and as the cells develop they cease to have the capacity to renew themselves. The photoreceptor cells, rods and cones have a significant problem; they are not only exposed to optical radiation throughout life but they have to transduce it in order to initiate vision.15-16 This process requires huge amounts of energy and as a consequence, the cells have an extraordinary high oxygen demand, being equipped with the highest concentration of mitochondria out of any cells of the body. Thus this non-dividing cell system is simultaneously exposed to an environment with extremely high levels of both oxygen and radiation. This combination is known to be extremely toxic to biological systems because of the induced generation of superoxide and other free radicals.17-20
The Beauty of the Inverted Retina
The next paradox is generated by the need to provide sustenance to the rods and cones in order to sustain their huge metabolic demand. This has been solved in all vertebrates by the evolution of the ‘inverted’ retina. At first it seems strange that the cells that do the transducing of light are on the side of the retina furthest from the incoming radiation. This apparent anomaly becomes understandable when the requirements for a blood supply to the light-sensitive cells is examined. If the photoreceptors pointed towards the incoming light then they would either have to have a large blood supply between them and the incoming light, limiting transmission and resolution, or a large blood supply between the photoreceptors and the next layer of neurones, limiting neuronal processing. The structure of the inverted retina avoids these issues by allowing the photoreceptor cells to derive their blood supply from the innermost aspects of the choroid via an acellular membrane, Bruch’s membrane and the pigment epithelium.21 This anatomical arrangement also enables the retinal pigment epithelium to act as an anti-halation screen, absorbing much of the unused radiation that has passed through the photoreceptor cells, preventing scatter and degradation of the retinal image.22
Auto-regenerative Capacity of Photoreceptors
The juxtapositioning of the photoreceptor cells and the retinal pigment epithelium also allows for a solution for the fourth paradox; how can non-dividing cells like the photoreceptors survive over our lifetime in an environment of high oxygen and with the function of absorbing and transducing optical radiation? The solution is unique amongst neurones. Throughout life the light-sensitive portions of the photoreceptor cells are constantly renewed. This exquisite process differs between rods and cones. Animal studies in rods demonstrated that three to five of the light sensitive membrane structures or discs are manufactured daily23-25 on the innermost aspect of the light-sensitive outer segment and as new discs are added, older discs are progressively displaced towards the retinal pigment epithelium.26-28 Typically a rod’s outer segment contains about 1,000 discs and thus, in theory, the whole system is replaced in approximately two weeks. When the older discs reach the surface of the retinal pigment epithelium they are phagocytosed in a process that seems to be initiated by the onset of light on first awakening in the morning.29-31 Therefore, the spent products from our night-time photoreceptors, the rods, are phagocytosed first in the morning and then undergo ‘digestion’ during the day by the action of lysosomes. By contrast, it would appear that our daytime photoreceptor cells, the cones, are phagocytosed four hours or so into sleep and undergo degenerative processes during the night.
Biomarkers of Ageing
This process of daily shedding of spent material from the photoreceptor cells presents a huge biomass to the retinal pigment epithelium and not surprisingly the system becomes compromised as a function of age. In most retinae, by the late 20s, persistent partially degraded debris becomes present within the retinal pigment epithelium and is seen as lipofuscin granules, which are autofluorescent and visible clinically.32-36 As a result of further ageing processes, debris begins to pass from the retinal pigment epithelium into the underlying Bruch’s membrane and may, in some cases, be seen in our 60s or 70s as focal excrescences termed drusen. Drusen are visible clinically and are identified as high-risk factors for age-related macular degeneration.37-41 In the outer retina we see then an exquisite protection mechanism to preserve the functional lifetime of the rods and cones by constantly regenerating the light-sensitive components, but one which ultimately leads to long-term problems by degrading the very transport mechanisms on which their survival depends. Regardless of the genetic make-up of any given individual photoreceptor cell, the function of outer segment material will be degraded by natural ageing processes and to some extent the rate-limiting steps of the degradation will be related to the rate of turnover of discs. Very simply, the outer retina has evolved to sustain the lifetime of non-dividing, highly specialised neurones, rods and cones, within a system that is irradiated by and absorbs optical radiation throughout life in a high oxygen environment. This system works extremely well over the period in which we should procreate but perhaps now, with ever-increasing life expectancy, it is not surprising that the system shows significant signs of fatigue with increasing age.
The Pathogenic Power of Light
Throughout evolution man has been exposed to light cycles of roughly 12 hours of daylight and 12 hours of darkness, with a further variance induced by the tilt of the Earth in summer and winter. The sun is by far the brightest light source that we are exposed to and has the broadest emission spectrum with radiations from the ultraviolet through the shorter wavelengths of infrared.42 Fortunately, our atmosphere shields us from the most damaging forms of optical radiation, in that very little ultraviolet C (100-280nm) reaches ground level, although the increasing depletion of the ozone layer with ‘holes’ over the Antarctic are of increasing concern.
Basic physics has long established the relationship between wavelength and energy. The shorter the wavelength, the higher the energy. In the electromagnetic spectrum, this is easily remembered because ultraviolet radiation sits next to x-rays, which are highly energetic while infrared is adjacent to microwaves. Simplistically, from ultraviolet through to the blue region of the spectrum, individual photons by themselves have enough energy to induce photochemical changes in absorbing molecules by themselves.10,43,44 By contrast, from the red region up through the infrared, individual photons no longer have sufficient energy to act by themselves. Damage mechanisms induced by radiation in these wavebands are by multiple photons causing vibrational modes in absorbing tissues and thermal damage. Thus in considering the potential hazards of any given light source, attention must be given to the spectral emissions and spectral radiances with blue rich sources being potentially much more damaging than those predominantly red or infrared.42,45 This has interesting implications for man’s artificial light environment.
The Challenges of New Indoor Lighting
For thousands of years, sources of light were dependent on burning wood, oil candles, gas etc. and thus were accompanied by heat. Efforts to increase illumination resulted in excessive heat, so the lit environment after nightfall was limited. The extent to which man was dependent upon solar radiation is seen in the prints of city life, such as the scenes of London by Gustaf Doré showing night-time life as very dim and depressing. To some extent we are the first generation to have daylight levels of illumination at the flick of a switch.
High levels of artificial lighting really came about with the advent of the fluorescent tube in the early 1940s. It took many years for the biologically harmonious incandescent lamps, which emitted very little blue and a spectrum predominantly in the red and infrared,42 to be replaced by fluorescent lighting in commercial and industrial establishments and then more recently, compact fluorescents and LEDs in the home. The drive by governments towards ‘low-energy’ lighting, has resulted in the proliferation of numerous sources rich in blue and some also emitting a little UV. Concern has also been expressed about the emission spectra of devices such as smartphones and tablets, which the media has erroneously identified as potential eye problems. While such systems do have a significant blue component in their screen emissions they are at such low levels that they do not in any way represent a biohazard.46 By contrast, LEDs have much higher spectral emissions in the blue and at levels that may require attention over cumulative exposures during a human lifetime.47-49
The Dark Side of Blue-violet Light
Interest in the potential damaging effects of light has extended over hundreds of years with claims that Galileo damaged his retina by viewing the sun through his telescope. This myth did not survive detailed study. However, many have damaged their vision by viewing the sun and systematic investigations began after the first explosion of the atomic bomb because of concerns about the associated flash. The real impetus came in the early 60s after the development of the laser. Extensive military budgets were deployed to ensure that the potential for lasers to damage the retina were fully understood and ocular safety mechanisms were explored. Numerous studies at this time demonstrated that with short intense exposures, lasers emitting blue light were a greater potential hazard than those in other regions of the spectrum.50-52 The peak of the ‘blue light hazard’ in a normal eye with a natural lens present was shown to be around 440nm,6,53 although this peak moved into the ultraviolet in individuals that had undergone cataract surgery.
Recent research has confirmed the peak of blue light hazard at 435nm, with an action spectrum from 415 to 455nm.10 The blue-violet light hazard is treated as a special case worldwide in all codes of practice designed to protect people against lasers. Further work showed that low-level irradiance, over very long periods – hours, days, months – also resulted in retinal damage, again highlighting that blue-violet light was more hazardous than other wavelengths.19,54,55 We now know that there are two mechanisms of light damage, with slightly different absorption or action spectra, but both peaking in the blue. For relatively low intensity and very long exposures, we see what is described as Type I damage, which appears to result from absorption within the light-sensitive cells and short wavelength or blue cones seem to be the most sensitive.52,56,57 By contrast, for relatively high intensity shorter exposures, we recognise Type II damage whereby the primary damage seems to occur in the retinal pigment epithelium58 and is thought to be associated with absorption by lipofuscin (as per Fig 2, 3).
It is of interest that within the eye there are two naturally occurring systems which attenuate blue light. In the natural lens, yellowing occurs with age limiting the passage of light towards the neural retina. At the centre of our vision, the macula, there is a second pigment, the luteal pigment, which is also yellow with an absorption peak at about 445nm.59,60 Further, at the centre of this region, the fovea, responsible for our highest acuity vision, there are no short wavelength, or blue photoreceptors, giving rise to the often forgotten phenomenon present in all of us; foveal tritanopia.61 These findings, on the potentially damaging effects of ultraviolet and blue radiation, led the companies that manufacture intraocular lenses to introduce ultraviolet blocking systems in all intraocular lenses. This occurred without any significant clinical trials and in today’s parlance in the absence of ‘evidence-based medicine’. Nevertheless few, if any cataract surgeons would now place an intraocular lens into a human eye that did not have UV filtration. It is of interest that over the past 15 years, many companies have introduced blue attenuating intraocular lenses. These lenses have an attenuation factor similar to that of a natural lens in its late 30s or early 40s. This has been a little more controversial because it arrived in the era of ‘evidence-based medicine’ but even in the absence of extensive long-term clinical trials it is still a system used by many informed surgeons.
The Beneficial Blue-turquoise Light
The apparent unimportance of blue light for vision has recently been challenged in the greater forum of blue light for overall health. In a series of studies it has been demonstrated that blue light in the region of 470nm (blue-turquoise light) is a fundamental requirement to initiate aspects of circadian rhythm.62-64 These studies have further demonstrated that a small percentage of retinal ganglion cells contain a pigment, melanopsin, whose absorption of blue light triggers a mechanism via the brain which regulates melatonin levels in the blood. When the retina is exposed to light with a blue component, the absorption within melanopsin initiates a process that supresses melatonin production and the individual exposed ‘wakes up’. By contrast, switching off absorption at night increases melatonin production and the individual goes to sleep (Figure 4). Therefore it is obvious that longer wavelength blue-turquoise light around 470nm is essential for well-being. Thus we have an apparent paradox whereby short wavelength blue-violet light at 441nm is potentially harmful, while longer wavelength blue-turquoise light at 470nm is essential for healthy living. Interestingly that the ganglion cells responsible for absorbing 470nm are anatomically arranged such that they occur prior to the components of the retina that absorb the harmful 441nm as light is transmitted from the cornea to the retina. Thus in our evolutionary development, both mechanisms have been integrated to facilitate separation of health and hazard.
Modern sources of artificial light have revolutionised our lit environment with the potential to flood our individual places of work or homes at levels of illumination far beyond that experienced by our ancestors. Almost daylight levels of illumination can now be achieved at any time of the day by flicking a switch and governmental trends towards the use of low-energy lighting have seen the development of many blue rich sources, in particular LEDs. This takes modern man out of the evolutionary boundaries determined by solar radiation into a new era. It will be interesting to monitor the effects of our new environmental boundaries on the health of the outer retina further complicated by our increased life expectancy and the increasing prevalence of age- related macular degeneration. We have learnt from the dermatologists that light contributes to photo-ageing, with UV and short wavelength visible playing a role. Given the increase in irradiance for any given exposure between the eye and the skin it seems sensible to limit our exposure to short wavelength radiation whenever possible. Most individuals use UV and light protection in high light environments by wearing sunglasses. Depending upon the absorption spectra, these can offer useful protection if they attenuate ultraviolet and short wavelength blue-violet. They can also be less than useful if they transmit these wavelengths yet, by reducing overall brightness, cause the pupil to open and individuals to stay in the sun for longer. The recent introduction of UVA blocking systems and attenuation of short wavelength blue-violet for everyday wear clear lenses seems a sensible development in the face of our ever-changing light environment.
|Key Points to Take Away|
· The penetration of optical radiation deep within the eye is a paradox as light is an essential component for vision, but it is also a biohazard.
· The inverted retina is designed to avoid scatter and degradation of the retinal image and to ensure efficient neuronal processing.
· The light-sensitive portions of the photoreceptor cells are constantly renewed to survive over a human lifetime, in an extremely toxic environment due to oxygen and light radiation.
· With ageing, the accumulation of lipofuscin in Bruch’s membrane may form drusen, identified as high-risk factors for age-related macular degeneration.
· LEDs have high spectral emissions in the blue and at levels that may require attention over cumulative exposures during a human lifetime.
· Retinal phototoxicity has been demonstrated by several studies for high energy wavelengths, with blue-violet light ranging up to 455 nm.
· Blue-turquoise light, ranging from 465 to 495 nm, is a fundamental requirement for circadian rhythm and thus essential to maintain good health and well-being.
· UV and blue-violet light are both responsible for skin and ocular photoageing. Therefore it is of great importance to limit our exposure to these radiations whenever possible