shown by Ayala et al. (2000) of. Sweden, the additivity of ... UVR-induced cataract (Ayala &. So¨derberg 2004). .... in this direction. Anna Midelfart. References.
ACTA OPHTHALMOLOGICA SCANDINAVICA 2005
Guest Editorial Ultraviolet radiation and cataract Acta Ophthalmol. Scand. 2005: 83: 642–644 Copyright # Acta Ophthalmol Scand 2005.
doi: 10.1111/j.1600-0420.2005.00595.x
I
t is sometimes difficult to evaluate the exact impact of research activity performed in ophthalmology in the Nordic countries on the progress of global scientific knowledge. As this activity is carried out in rather small research communities, it is not possible to cover all aspects of basic ophthalmological research, perform large-scale epidemiological studies, or involve hundreds of patients in clinical trials. However, based on the longstanding tradition of extensive co-operation between the Nordic countries, our contribution might be higher than we would expect. Basic cataract research performed in the Nordic countries during recent years, and presented in part at the Nordic Meeting in Malmo¨ in 2004, can be used as an example to illustrate this situation. Cataract is the leading cause of blindness worldwide; it is responsible for loss of sight in about 25 million people and accounts for around 50% of all blindness (Munoz & West 2002). Because of the increasing life expectancy, particularly in heavily populated countries such as India and China, the importance of preventing cataract or delaying its progression has been emphasized (McCarty et al. 2000; West 2004). Although safe, effective surgery is available to improve vision, strategies for primary prevention could potentially reduce the need for cataract surgery and decrease health care costs. Exposure to ultraviolet radiation (UVR) from the sun is one of the
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widespread risk factors for cataract development. Eye exposure is determined by several factors, such as atmospheric conditions, reflection from the environment, geographic location, and the anatomical position of the eye. The temporal side of the eye is most vulnerable to solar UVR, focusing the light on the nasal part of the cornea and lens (Sasaki et al. 2003). The cornea blocks almost all radiation with a wavelength of 290–300 nm, with gradually increasing transparency towards longer wavelengths. The lens absorbs most UVR up to 380 nm (So¨derberg 2004). Safety limits for UVR exposure of the human lens have to be based on animal experiments. Recently, a Swedish research group (So¨derberg et al. 2003) presented a new method for experimental estimation of the maximum acceptable dose (MAD) for toxicity of UVR to the crystalline lens. As pointed out by Lo¨fgren et al. (2003) and Lo¨fgren (2004), the lack of standardized protocols makes it difficult to compare results from different studies, particularly those performed with different animals of both sexes and various ages. Thus, we need more data to refine established safety limits. Some important facts have been gradually added to our knowledge. As shown by Ayala et al. (2000) of Sweden, the additivity of repeated exposure to UV radiation has to be considered. The results of this research have shown that, whereas repeated UVR exposure separated by 3 days gave rise to synergistic additivity in the lens, only partial additivity was
found when UVR exposures were separated by a 30-day interval, presumably due to repair of the damage. According to the experiments performed by Dong et al. (2003), the sensitivity of the lens towards UVR varies over the course of a lifespan, and is most sensitive at a younger age. It is therefore very important to introduce an age factor to current safety standards. Finally, in animal models, oral administration of vitamin E was found to protect against UVR-induced cataract (Ayala & So¨derberg 2004). In co-operation with the Swedish research group, Norwegian researchers applied nuclear magnetic resonance (NMR) spectroscopy to study the metabolic changes occurring in the anterior segment of the eye due to UVR (Midelfart 2004). Based on the metabolic profiles obtained for the normal eyes (Gribbestad & Midelfart 1994; Midelfart et al. 1996a, 1996b, 1996c), it was possible to follow changes induced by UVR in the aqueous humour, cornea and lens. Exploiting new technology, a special technique, magic angle spinning (MAS) NMR spectroscopy was applied for the first time to study eye tissue (Risa et al. 2004). This technique allows intact samples from the cornea and lens to be analysed directly, avoiding the need for extraction or purification. The results revealed significant changes in the concentration of many water-soluble metabolites in the rat lens induced by UVB in different doses, including taurine, hypotaurine,
ACTA OPHTHALMOLOGICA SCANDINAVICA 2005 myo-inositol, ascorbate, glutathione and several amino acids. In the rabbit eye, the metabolic changes were enhanced after longterm topical steroid treatment before the UVR exposure (Sæther et al. 2004). Furthermore, UVB was found to have a larger impact on the metabolic profile of aqueous humour than UVA (Tessem et al. 2005). A Czech group then became involved in this series of co-operative studies, bringing with it the results from its enzymatic studies, which supported the findings from the metabolic analyses. These were also presented in Malmo¨. In contrast to UVB rays, UVA did not evoke profound enzymatic disturbances in the rabbit cornea (Cejkova et al. 2003; Cejkova 2004). Interestingly, as shown by Ehlers (2004), UVR can be favourably utilized for re-modelling the cornea. Thus, the cross-linking of collagen induced by combining riboflavin and UVA treatment was found to increase the stiffness of the corneal stroma. This UVR effect was linked to up-regulation of the structural proteins decorin and actin. In the future, this strengthening effect of UVA on the corneal stroma might be utilized for corneal re-modelling, with particular importance for keratoconus. Previous epidemiological studies have shown a significant frequency of cataracts in populations that have a high annual exposure to sunlight and UVR (McCarty & Taylor 2002). The Reykjavik Eye Study provides epidemiological support for UVR damage to the eye (Katoh et al. 2001; Jonasson et al. 2004). Thus, substantially higher odds ratios for cortical cataract were found in people who spend more than 4 hours outside in the daytime during their 20s to 30s and their 40s to 50s in comparison with people who spend hardly any time outside during the day. No similar relationship was found for nuclear cataract, although smoking was found to increase the risk of nuclear opacification (Arnarsson et al. 2002). Cigarette smoking is thought to increase the oxidative stress in the lens, leading to development of cataract (Hirvela et al. 1995; Leske et al. 1998; McCarty et al. 2000). The effect of smoking cessation is, however, not entirely clear. Recently, the possible benefit of stopping smoking in relation to the risk of cataract among women was examined in Sweden
(Lindblad et al. 2005). This prospective study confirmed smoking as a risk factor for cataract, with a dose– response relationship according to the level of smoking. Smoking cessation results in a reduced risk over time, but a longer period of time is needed to reduce the risk if the subject has been a heavy smoker. This study represents an important contribution to the discussion about cataract prevention, showing that smoking is an obvious risk factor for cataract and abandoning smoking should be recommended at ophthalmic consultations and visits. These examples, which by no means represent a complete overview of all research activity in this area, illustrate the high level of contribution made by Nordic research groups in ophthalmology research. In my opinion, the greatest potential for enhancing the impact of this research activity is to further expand research co-operation between the research groups in Scandinavia, with simultaneous focus on international collaboration. The establishment of the Nordic Academy of Ophthalmology as the headquarters for the co-ordination and promotion of research activity in the Nordic countries represents an important first step in this direction. Anna Midelfart
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