Eye (1987) 1, 282-295 The Ageing Retina: Physiology or Pathology JOHN MARSHALL London Summary The human'fetina is a unique component of the nervous system in that throughout life it is continuously exposed to optical radiation between 400 and 1400 nm. The physiology of the ageing retina and the regression in visual performance with age cannot therefore be studied in isolation, or discriminated, from the life long cumulative effects of radiant exposure. This paper describes the spectrum of age related changes in the retina as they merge imperceptibly between declining visual function and overt pathology. Functional Loss ponents, the larger one being diminished Virtually every measure of visual function transmission by the ageing lens and a smaller demonstrates declining performance with one induced by neuronal changes in the age­ increasing age.! However, since all the com­ ing retina and cortex. ponents of the eye age in different ways it is Age related degradations in visual acuity5.6 essential when assessing changes in retinal or and contrast sensitivity7,8 have been docu­ neural function to allow for changes in the mented for many years9 and are especially stimulous incident upon the retina due to evident over the age of 60 years. 5 Recently the either perturbations in the optic media or use of sinusoidal grating patterns generated physiological processes in the anterior eye. by a laser interferometerlO has enabled the For example, in the older eye the retinal irra­ independent assessment of degradation of the diance achieved by a given source with a given image quality by the optic media and the geometry will be less than that in a young eye effective loss in resolving power of the neuro­ because of a reduced pupillary diameter nal components in the visual system.Il,12 The (senile miosis), and decreasing transmission conclusion from such studies is that the age and increasing fluorescence properties of the related deterioration in contrast sensitivity is cornea and lens. The latter will also modify primarily caused by changes within the neuro­ the spectral irradiance as absorption and scat­ nal elements of the visual system. 12 ter in the ageing lens and cornea are more significant for shorter wavelengths.2 Ageing Populations The practical difficulties in relating a par­ Given the increasing socioeconomic impor­ ticular functional loss to a specific anatomical tance of rapid assimilation of visually site are slowly being resolved. For example communicated information any impairment McFarland and colleagues3 demonstrated a of vision severely handicaps the performance two times elevation of threshold in the dark of everyday tasks. As the handicap progresses adapted eye for every year over the age of 20. economic and social dependence of the Subsequently Gunkel and Gouras4 showed affected individual increases accordingly, that this elevation resulted from two com- Whilst a detailed analysis of population Correspondence to: Professor John Marshall, Department of Clinical Ophthalmology, Institute of Ophthal­ mology, Judd Street, London WCIH 9QS, THE AGEING RETINA 283 dynamics is beyond the scope of this article it such systems is phenomenal with entire cell is worth highlighting some worrying trends in populations changing every one to six days the industrialised world. In many western depending upon the tissue. Each day, some countries an increase in life expectancy 500,000,000,000 cells are shed and replaced coupled with a falling birth rate is giving rise to throughout the body, and in an average life­ ageing populations, for example, by the end time cell populations may renew more than of this decade 15.5 per cent of the population 12,000 times. In contrast cells in non-dividing of theUnited Kingdom will be over the age of systems are usually found in highly differen­ 65.13 Within this population there will be 2 tiated forms and do not undergo nuclear divi­ million more women than men, a finding of sion after their initial development in early significance as there is evidence that many embryonic life. senile eye conditions have an earlier onset and A special problem occurs when a rapidly a higher incidence in women.14 Perhaps more resynthesising cell system is trapped between worrying is the fact that the elderly constitute two non-dividing systems. In such a situation the major patient load for ophthalmic practi­ one or both of the non-dividing systems may tioners as there is a dramatic rise in the inci­ suffer secondary damage as a result of coping dence of ocular pathologies in this group. In a with the waste products generated by the trap­ recent study based on government sources the ped dividing system. figures for blindness in England and Wales were quoted as less than 10 per 100,000 in the age group 0-4 years and rising to 5,200 per Molecular Ageing 100,000 in the over 75 year 0lds.1s The figures At a molecular level both cell systems are whilst disturbing in themselves become much undergoing constant renewal and replace­ more worrying when extrapolated on the basis ment. Indeed it is this very process of continu­ of the Melton Mowbray study16 which would ous self synthesis that defines life (i.e. the suggest that blindness in the elderly is under­ maintenance of biological integrity). The only estimated, in government figures by at least exception to this process of constant molecu­ one third. Of this elderly blind patient group lar formation and degradation is the genetic approximately 20 per cent will have been reg­ material itself, DNA, which in non-dividing istered because of cataract, but between 46 systems is perfectly stable. However even and 50 per cent will be the result of macular here if a lesion occurs in the double helix then disease. In essence senile macular degenera­ special enzymes detect it, remove the tions are now the leading cause of blindness in damaged part and attempt to replace it. This . the western world. unique process of molecular repair rather than replacement has only been described for Cellular Ageing DNA, and unlike the constant process of The ageing process is usually monitored by molecular replacement it is only initiated by reference to a single biologically independent the presence of damage in the double helix. variable, the passage of time.17 As a result it is Continued cell life is dependent on not often mistakenly considered as a solitary pro­ exceeding or overwhelming this repair pro­ cess. This is clearly not the case as at a cellular cess. DNA damage may result from a cell level even the most simplistic approach must being irradiated by high energy photons in recognise the differences between those cell short wavelength light or ultra violet radiation systems undergoing cell division throughout and the repair process may slow down with life and those systems that do not. For clarity age. Both of these concepts will be discussed we can designate the former cells as 'Dividing' later. and the later to 'Non-dividing' categories. Molecular replacement is the cell's answer Dividing systems are usually relatively simple to the principle of entropy whereby all natural cells and are found in locations where cells are processes strive to dissipate energy and under constant attack from physical agents, thereby exist in an increasing state of dis­ such as surface cells of skin or cornea, or cells order. Any living cell is a highly ordered lining the gut. The rate of cell replacement in system and expends large amounts of energy 284 JOHN MARSHALL to retain its ordered structure by constantly oped inner segments. In all other locations the renewing it. presumptive photoreceptor cells are still The rates of molecular renewal vary dra­ undergoing mitotic division. For some as yet matically for example the aqueous humour is unexplained reason further development of renewed every 1 to 1.5 hours. IS In contrast the macular photoreceptor cells then seems to proteins incorporated in rod disc membranes cease, and those in the rest of the retina last for two weeks19 whilst those constituting rapidly overtake them during the remaining the axoplasmic framework in a human retinal months in utero. At birth the macular photo­ ganglion cell may exist for 3 months or more. receptors are the most poorly developed, and In the latter case during their lifetime they do not reach full maturity until at least four to slowly migrate from their site of synthesis in six years post-partum.22 the cell body to their site of destruction at their synapses in the optic tectum.20 Several The Adult Macula factors also influence the rates of molecular As ageing of the macula is the most significant renewal, including nutrition, temperature, clinical problem, discussion will concentrate and radiant exposure. The latter exerting its on this region. The term macula means patch, effect both in the establishment of diurnal and to some extent this conveys the clinician's rythms in biological organisms, and by induc­ dilemma in defining the boundaries of this ing photochemical changes in macro­ region. Ophthalmoscopically an individual molecular systems. Diurnal rythms operate at macula is considered to be an area centred on both a cellular and molecular level, and there the fovea throughout which there is an altered are many reports in the literature describing light reflexwhen compared with the surround­ cyclic fluctuation in mitotic activity and pro­ ing fundus. The origins of this altered light tein synthesis according to the time of day or reflex are complex with contributions from an night.20 Photochemical processes always altered retinal thickness, densely pigmented create problems for cells as the reaction prod­ retinal pigment epithelium and the presence ucts or intermediaries are often toxic, how­ of a yellow pigment, the macula lutea.23 The ever in most natural exposures the cell's extent of the ophthalmoscopic macula is defence mechanisms or renewal systems can highly variable between individuals, but com­ cope with the extra stress.