Eye (1987) 1,304-310 Light and Macular Degeneration: A Biophysical and Clinical Perspective MARTIN A. MAINSTER Kansas City, Kansas Summary The evidence linking photic retinopathy to ageing macular degeneration (AMD) is compelling but circumstantial. The biophysical foundations of ageing theory are presented, in addition to an analysis of retinal senescence ",ndthe potential contribu­ tory role of photochemical retinal damage. Although there is pressure to implement clinical therapy for AMD based on laboratory studies of photic retinopathy, there is no evidence at this time that any such therapy is effective. Nonetheless, until the relationship between photic retinopathy and AMD is better understood, it is appro­ priate for individuals to use ultraviolet and deep blue protective sunglasses in bright environments, particularly if they have reduced ocular pigmentation or if they are aphakes or pseudophakes without an ultraviolet-protective intraocular lens. Time and ageing moving backwards in time, when we deal with Notions of time are implicit in all studies of phenomena involving large numbers of parti­ ageing. In contemporary physics, time is cles, entropy offers a direction for time's merely another dimension, and there are no arrow. Entropy is a measure of a system's dis­ privileged moments such as 'now'. Confusion order, and it either remains constant or arises because relativity theory offers con­ increases in any closed system. Entropy pro­ vincing evidence that the magnitude of a time vides only temporal asymmetry. It does not tell interval depends on the velocity and location how rapidly 'now' moves into the future, only (local space-time curvature) of the observer. that the universe appears differently when Thus, the 'now' of two different observers may viewed forward or backward in time. proceed at different rates, and the 'nows' of a All living systems are open systems that can group of humans are readily desynchronised exchange matter and energy with their sur­ by differences in their velocities and locations. roundings. Since living systems are open, In other words, 'now' may not extend beyond entropy can decrease temporarily during life, 'here'. as manifested by the highly improbable Physics does not provide an explanation for ordered structure of living systems. The the subjective concepts of 'now' and the 'flow dynamic order of living systems probably of time', but it does address the issue of the arises because of self-organising fluctuationsin direction of time's arrow.! Although useful these open, far-from-equilibrium systems theories have been developed to explain sub­ ('dissipative' systems).2 .3 The laser is a familiar microscopic phenomena in terms of electrons example of a dissipative system in which there This research was supported in part by Research to Prevent Blindness, Inc and Kansas Lions Sight Foundation, Inc. Correspondence to: Martin A. Mainster, M.D., Ph.D., Department of Ophthalmology, Kansas University Medical Center, 39th and Rainbow Boulevard, Kansas City, Kansas 66103. LIGHT AND MACULAR DEGENERATION 305 is self-organisation of coherent emitters. The tor-RPE juncture).6,7 Constant light blocks photoreceptor and retinal pigment epithelium disc shedding but maximises disc production, (RPE) cell are further examples of dynamic, resulting in longer rod outer segments. Short­ self-organising, open, non-equilibrium, ened light periods and reduced temperature space-time structures that arise, and after a reduce disc production, resulting in shorter variable period of time, decay. The openness rod outer segments. Rod and cone disc shed­ of cellular systems is the basis of life and death. ding occurs after light onset and offset, respec­ It is also the basis for our hopes to findmethods tively. Disc shedding and replacement provide for increasing the time interval in which an effective method of eliminating outer seg­ humans and their retinae function properly. ment damage caused by light or other detri­ mental influences, but place a metabolic load Retinal Senescence on adjacent RPE cells responsible for pha­ After development, organisms and their com­ gocytosis and degradation of the phagosomes. ponents deteriorate structurally and func­ In the aged retina, lengthy, convoluted rod tionally. There is a remarkable similarity in the outer segments are observed, suggesting rate at which organ systems decline, however, impaired disc shedding, possibly because of prompting numerous vain attempts to find a diminished RPE function. 8 single unified 'cause' for ageing. Over the The RPE is also a delicate balance, between years, causes proposed for ageing have paral­ ingestion of outer segment tips apically and leled areas of contemporary research interest, apoptosis of RPE cytoplasm basally.9 Since the including toxic products of intestinal bacteria, RPE is subject to the damaging effects of lipid hormone deficiencies, dehydration of body oxidation in an oxygen-rich environment, it colloids, latent viruses or lethal genes, and free has evolved a variety of defense mechanisms radical toxicity. Adding to the complexity of including anti-oxidants such as superoxide dis­ the problem are recent statistical studies show­ mutase, peroxidase, catalase andvitaminE. In ing that psychiatric factors influence rates of addition, light absorption by melanin helps ageing and death.4 Bell's interconnectedness defend against high light levels, and melanin theorem adds further complexity, establishing acts as an electron transfer agent. The RPE and non-local reality at an even more fundamental sensory retina are also protected by macular level, and forcing us to choose either objec­ xanthophyll.10 In senescence, there is an tivity (i.e. a world that exists in a definitestate increase of RPE melanolipofuscin, apart from measurement) or local causality melanolysosomes and lipofuscin,l1 and a (i.e. systems can be influenced only by medi­ decrease in RPE melanin11 and probably other ated interactions travelling no faster than the defense mechanisms. Surprisingly, the great­ speed of light). 5 est increase in lipofuscin occurs between the While we have far to go in our search for a firstand second decades of life (rather than in unified theory of ageing, the retina does not old age), with the melanin to lipofuscin ratio exist independently of its host body, and it is reversing from 2: 1 to 1: 2 by the end of the unlikely that the problem of retinal ageing will second decade.11 One may speculate that the be solved by studies limited to the retina. continuing increase of lipofuscin and other Nonetheless, the retina does have unique debris leads to a decrease in functional characteristics, and the identification and cytoplasmic space and progressive failure of modification of deleterious influences may transport, phagocytic and other metabolic permit prolongation of retinal function. Light functions of the ageing RPE cell. is one such influence.Its effects are manifested Ageing of Bruch's membrane is due in part primarily at the level of the photoreceptor, to deposition of RPE cytoplasmic debris, RPE and Bruch's membrane. resulting in basal laminar deposits above the Photoreceptor outer segment structure is a RPE basement membrane, and drusen on or delicate balance between disc production at within the inner collagenous layer.9,12 In addi­ the proximal end of the outer segment and tion, there is mineralisation of the inner col­ periodic shedding of packets of discs at the dis­ lagenous and elastic layers. It is probable tal end of the outer segment (the photorecep- though not currently proven that most RPE 306 MARTIN A. MAINSTER cytoplasmic debris passes through Bruch's radiation which varies periodically in intensity membrane to the choroid. This is consistent as the earth spins on its axis and orbits the sun. with the observation that cytoplasmic debris is Complex systems operate by periodic transfor­ often absent from the inner collagenous layer mation of energy into work, and many biolog­ underlying drusen, suggesting that drusen may ical systems exhibit a circadian rhythm that is result from blockage of the transport of debris largely independent of temperature and through the inner collagenous layer to the environmental influences. choroid. 9 The photoreceptor and RPE cell are com­ As the retina ages, retinal thickness plex open systems, incorporating autocatalytic decreases, probably in part from a loss of reti­ chemical reactions, undergoing auto-oscilla­ nal neurons and photoreceptors. Drusen are tions in structure and function, dependent on the earliest ophthalmoscopic sign of ageing the provision of essential raw materials and the macular degeneration (AMD). They can removal of cellular debris, and existing in a remain stationary, coalesce, or lead to large dynamic order subject to numerous local geographic areas of atrophic RPE. Serous catastrophes. This complex, dynamic order drusen are often harbingers of exudative eventually collapses in senescence. While we AMD, which is present in only 10 per cent of readily appreciate changes at individual points patients with AMD, but responsible for 90 per in time (such as lipofuscin accumulation), or cent of all serious visual loss due to AMD. 13 In those occurring during short intervals of our exudative AMD, choroidal neovascularisa­ life (such as choroidal neovascularisation), we tion may cause haemorrhagic detachment of may fail to observe very slowly evolving the RPE and/or sensory retina, producing a dynamic changes equally fundamental to our disciform macular scar