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Download Figure.8: Dtto for age-related macular degeneration It is reassuring
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Figure.8: Dtto for age-related macular degeneration It is reassuring to find that all the cumulants lie below the (prevalence) data indicative of the age-related risk of open-angle glaucoma, cataract, and age-related maculopathy respectively. Note that, in Figure 6, nearly all the points for glaucoma lie between the two theoretical lines. The present model would interpret this as implying that this condition is relatively free from environmental factors, and is mainly due to genetic causes. Compare this with Figure 7 for nuclear cataract. In this case only the younger cases fall within the genetic limits, whereas the later ones fall outside them, Cataracts are known to take several, sometimes many, years to develop: the model suggests that the late-onset cases may be due more to environmental than to genetic causes. Indeed, a number of controllable risk factors, such as diet, smoking, lack of vitamins, have been mentioned in the literature. Finally, Figure 8 shows data for age-related maculopathy, and virtually all of them appear to lie outside the limits defined by the two theoretical curves. This suggests that the environment may play a dominant role in the pathogenesis of this condition, a conclusion which has received support for example from the observation that there has been a surge in the prevalence of the condition in Japan. Note that, in so far as hypertension may be the result of diet, it should be classed as an environmental risk factor. It will be appreciated that all statistics are retrospective. In the examples just discussed we have to remember that the data on biological functions are much harder to update than is true of the clinical and demographic ones. While the biological data may have been obtained under temporarily optimal conditions, they are probably tarred by adverse environmental conditions much as is true of the clinical data. I have already hinted at the possibility that mortality amongst the oldest old may fall in the future as we move into a wider non-smoking era and one in which the environment is generally improved. Insofar as there are environmental risk-factors, notably in connection with nuclear cataract and age-related maculopathy, but also as regards glaucoma, the future prevalences should also begin to fall. Just as there are improvements in both life expectancy and in general health expectancy, especially amongst the better off, so we can expect improvements in eye-health. There are, however, two principal obstacles to rapid improvements: first, once avoidable risk factors have been established, it is very difficult to change people's cultural make-up and inclinations in exchange for long-term health benefits, as the smokers amongst you will agree. Researchers have not yet learned to communicate sufficiently well, and the public have hearing and reading problems. Secondly, we are ignorant of the causes of these age-related eye diseases. Insofar as there are genetic propensities, it is likely that advances in molecular genetics will hold one of the keys to success, as is happening with some of the more distressing congenital anomalies. The control of environmental hazards is, or should be, in our hands. New surgical procedures are under way. For example, efforts are being made to transplant healthy tissue into diseased retinae to combat maculopathy. More and more pharmacological means are reaching the market to stabilize glaucoma. Here much more could be done by the wide-spread promotion of screening methods, although, again, this might not lead to the prevention of the disease but rather to that of its more distressing consequences. All three conditions show wide-spread variations across the world. Yet our knowledge of the anatomy, physiology, and pathology of the eye is based very largely on white Caucasian eyes. White is neither right nor universal, and it seems to me that a determined effort to understand ethnic differences in risk-factors might provide a first step toward the unravelling of these very secretive disease processes. But there is another step that needs consideration. It concerns politics. There will be few more devoted Europeans than myself, but I have to say that I was disappointed when the European Commission passed a few years ago a requirement that all large-scale users of word processors and computers should have an automatic right to routine annual eye-tests. Given the limited resources of ophthalmic services, the resultant squeeze this is bound to put on those who have clinical needs - and that includes the older majority - the decision seems to me to have been antisocial. Secondly, neither financial nor intellectual resources have so far proved to be inexhaustible in any part of the World. We observe that limited clinical resources are being devoted to essentially cosmetic procedures, such as the modification of the shape of the cornea, so that people may dispense with the wearing of glasses: as a result, meeting real clinical needs is put on the backburner, and we have to ask ourselves whether our socio-medical priorities have been sorted in the right order. To conclude, there are grounds for looking toward a future with reasonably optimistic eyes, but in my view it is important for us to recognize that all of us have to contribute to its formation. References Nette, E. G., Xi, Y.-P., Sun, Y.-K. Andrews, A. D. and King, D. W. (1984). A correlation between aging and DNA repair in human epidermal cells. Mech. Ag. Dev., 24: 283-292. Strasser, H., Tiefenthaler, M., Steinlechner, M., Bartsch, G. & Konwalinka, G. (1999). Urinary incontinence in the elderly and age-dependent apoptosis of rhabdosphincter cells. The Lancet, 354:919-919. Harding, J. J. (1970). Free and protein-bound glutathione in normal and cataractous lenses. Biochem. J., 117: 957-960. Weale, R. A. (1999). The senescence of the eye in relation to glaucoma. Communication to the Glaucoma Society, London. Strehler, B. L. (1986). Genetic instability as the primary cause of human aging. Exper. Geront. 21: 283-319. Clark, R., Zigman, S. & Lerman, S. (1969). Studies on the structural proteins of the human lens. Exp. Eye Res. 8; 172-182. Wood, A. M. & Truscott, R. J. W. (1994). Ultraviolet filter compounds in human lenses: 3hydroxykynurenine glucoside formation. Vision Res. 34; 1369-1374. Lerman, S. & Borkman, R. F. (1979). A molecular model of lens aging, nuclear and cortical cataract formation. Metab. Pediatr. Ophthal. 3:27-35. Siebinga, I., Vrensen, G. F. J. M., Otto, K., Puppels, G. J., De Mul, F. F. M. and Greve, J. (1991). Age-related changes in local water and protein content of human eye lenses measured by Raman microspectroscopy. Exp. Eye Res. 53; 233-239 Sweeney, M. H. J. & Truscott, R. J. W. (1998). An impediment to gfutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract. Exp. Eye Res. 67; 587-595. Borchman, D., Byrdwell, W. C. & Yappert, M. C. (1994). Regional and age-dependent differences in the phospholipid composition of human lens membranes. Invest, ophthal. Vis. Sci. 35; 3938-3942. Takemoto, L. (1996). Increase in the intramolecular disulfide bonding of alpha-A-crystallin during aging of the human lens. Exp Eye Res 63; 585-590. Duncan, G., Hightower, K. R., Gandolfi, S.A., Tomlinson, J. SMaraini, G. (1989). Human lens membrane cation permeability increases with age. Invest. Ophthal. Vis. Sci. 30; 18551859. Moffat, B. A., Landman, K. A., Truscott, R. J. W., Sweeney, M. H. J. & Pope, J. M. (1999). Age-related changes in the kinetics of water transport in normal human lenses. Exp. Eye Res. 69; 663-669. Duindam, J. J., Vrensen, G. F. J. M., Otto, C. & Greve, J. (1996). Aging affects the conformation of cholesterol in the human eye lens. Ophthal. Res. 28(suppl); 86-91. Sato, H., Borchman, D., Ozaki, Y., Lamba, 0. P., Craig Byrdwell, W., Yappert, M. C. & Paterson, C. A. (1996). Lipid-Protein Interactions in Human and Bovine Lens Membranes by Fourier Transform Raman and Infrared Spectroscopies. Exp. Eye Res. 62; 47-53. Grierson, I., Howes, R. C. & Wang, Q. (1984). Age-related changes in the canal of Schlemm. Exp. Eye Res. 39; 505-512, De La Paz. M. A., Zhang, J. & Fridowich, I. (1996). Antioxidant enzymes of the human retina: effect of age on enzyme activity of macula and periphery. Curr. Eye Res. 15; 273278. Weale, R. A. (1997). Human biological decline and mortality rates. Mech. Ageing Devel. 97; 55-72. Weale, R. A. (2000). Unpublished results. Albon, J., Karwatowski, W. S. S.. Avery. N.. Easty, D. and Duance, V. C. (1995). Changes in the collagenous matrix of the aging human lamina cribrosa. Brit. J. Ophthal. 79; 368375. Grunwald. J. EXP. Hariprasad, S. M. & DuPont, J. (1998). Effect of aging on foveolar chroidal circulation. Arch. Ophthal. 116; 150-154. Alvarado, J., Murphy, C., Polansky, J. & Juster, R. (1981). Age-related changes in trabecular meshwork cellularity. Invest. Ophtaht. Vis. Sci. 21; 714-727. Groh, M. J. M., Michelson, G., Langhans, M. J. & Harazny, J. (1996). Influence of age on retinal and optic nerve head blood circulation. Ophthalmology 103; 529-534. Wolf, E., Bell, B.. McFarland, R. A. & Podolsky, S. (1977). Visual perception and communication. In "Handbook of the psychology of aging" (eds J. E. Birren and K. W. Schaie), p-506. Van Nostrand, London. Cingle, K. A., Kalski, R. S., Bruner, W. E, O'Brien, C. M., Erhard, P. & Wyszynski. R. E. (1996). Age-related changes of glycosidases in human retinal pigment epithelium. Curr. Eye Res. 15; 433-438. Schmidt, S. Y. & Peisch, R. D. (1986). Melanin concentration in normal human retinal pigment epithelium. Invest. Ophthal. Vis. Sci., 27; 1063-1067. Keunen,J. E. E., Van Norren, D. & Van Meel, G.J.(1987). Density of foveal pigments at older age. Invest. Ophthal. Vis. Sci., 28; 985-991. Grunwald, J. E., Piltz, J., Patel, N., Bose, S. and Riva, C. E. (1993). Effect of aging on retinal macular microcirculation: A blue field simulation study. Invest. Ophthal. Vis. Sci. 34; 3609-3613. Fisher, R. F. (1987). The influence of age on some ocular basement membranes. Eye 1; 184-189. Ayers. S. C., Warner, G. L., Smith, K. L. & Lawrence, D. A. (1986). Fluorimetric quantitation of cellular and non-protein thiols. Analytic. Biochem. 154; 186-196. Quoted in : Marmor, M. F. & Wolfensberger, T. J. (1998). The retinal pigment epithelium, p.686. Oxford: Oxford University Press.