Oxidative stress and age-related cataract

Age-related cataract is a clouding of the lens that leads to decreased vision. It increases with age and is one of the leading causes of blindness worldwide. The only treatment currently available is surgery. Therefore, it is important to identify modifiable risk factors for cataract prevention. The cause of cataract is not fully understood and may be multifactorial, involving oxidative stress, a condition of disrupted balance between oxidants and antioxidants. Oxidative damage to lens proteins and lipids is suggested to be involved in the development of cataract. Antioxidants may protect against oxidative damage. The aim of this thesis was to examine factors related to oxidative stress, including biomarkers of exogenous/dietary and endogenous antioxidants, and systemic oxidative stress and inflammation, as well as vitamin supplement use and physical activity, with the risk of age-related cataract. The studies were based on women and men, born 1914-1952, in the population-based Swedish Mammography Cohort and the Cohort of Swedish Men. Information on diet and lifestyle factors was obtained from a self-administered questionnaire at baseline. Cases of age-related cataract were identified through linkage to registers. The relationship between exogenous/dietary and endogenous antioxidants was examined in a cross-sectional study of women with and without a history of chronic diseases. High fruit and vegetable intake and high levels of plasma carotenoids were associated with lower plasma extracellular superoxide dismutase activity (an endogenous antioxidant enzyme) in healthy women but not in women with a history of chronic diseases. In a nested case-control study including women with and without incident cataract, higher levels of urinary 8-iso-prostaglandin F2α (a biomarker for systemic oxidative stress) were associated with increased risk of cataract, but no association was observed for 15-keto-dihydro-prostaglandin F2α (a biomarker for systemic inflammation). The association between dietary supplement use and risk of cataract was investigated prospectively in the cohorts. The use of single, high-dose supplements of vitamin C or E, as well as B vitamins, but not multivitamins (usually containing vitamin doses close to recommended daily intake), was associated with increased risk of cataract. The use of vitamin C supplements in combination with some oxidative stress-related factors, such as age and corticosteroid use, as well as in the long-term, may be associated with even higher risk. The association between physical activity and risk of cataract was also examined prospectively. Higher levels of total physical activity, especially long-term, and specific subtypes including walking/bicycling and work/occupational activity, were associated with lower risk of cataract in women and men. Conversely, high leisure time inactivity levels were associated with increased risk of cataract. In conclusion, these results suggest that maintaining low systemic oxidative stress by having a healthier lifestyle, including eating a diet rich in antioxidants instead of taking high-dose supplements and being physically active may prevent cataract development in the general population