Influence of exposure patterns and oxidation in UVR-induced cataract

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Clinical Neuroscience

Sammanfattning: Background: Ultraviolet radiation (UVR) is one among a number of possible factors that may lead to the development of cataract. Whereas induction of cataract as the result of onetime exposure to UVR has been studied extensively, the data on lens damage resulting from repeated exposures to UVR are scarce. The Bunsen-Roscoe law of photochemical reaction (also known as the reciprocity law) states that if the products of time of exposure and irradiance are equal, then the quantities of material undergoing change will be equal. Vitamin E is an antioxidant with essentially unknown effects during lens aging and cataractogenesis. The p53 gene is related to apoptosis, an important phenomenon in cells, incuding the lens cells. Aims: 1. To investigate the additive effects of radiation exposure in UVR-induced cataract. 2. To evaluate the validity of the reciprocity law for UVR-induced cataract. 3. To deter mine whether vitamin E may protect against UVR-induced cataract. 4. To investigate the influence of vitamin E in the application of the reciprocity law for UVR induced cataract. 5. To investigate whether p53 expression increases after UVR exposure. Methods: Common for all five studies was the unilateral use of 300 nm UVR in vivo exposure of Sprague-Dawley rats. The degree of cataract was quantified by measurement of forward light scattering in the lenses. In the first study (additivity), rats received two UVR exposures of 4 kJ/M2 at increasing intervals (6 hours, 1 day, 3 days, 9 days and 30 days). In the second study (reciprocity), each rat was exposed to 8 kJ/m2 UVR for a different length of time (5, 7.5, 11, 15, 30, 60, and 120 minutes). In the third study (vitamin E and cataract) rats were fed vitamin E or not and then exposed to UVR. In the fourth study (vitamin E and reciprocity), vitamin E was added and rats were exposed to UVR for 5 or 15 minutes. In the fifth and final study rats were exposed to UVR and p53 gene expression was measured using reverse transcriptase polymerase chain reaction (RT-PCR). Results: In the first study (additivity), highest light scattering was found in the group with a 3-day interval between exposures. In the second study (reciprocity), the group exposed to UVR for 15 minutes showed the highest level of light scattering. In the third study (vitamin E and cataract), the vitamin E-treated group showed less light scattering than the control group. In the fourth study (vitamin E and reciprocity), no significant difference in forward light scattering was found among the lenses treated with vitamin E and exposed for 5 versus 15 minutes. In the fifth study p53 expression was 147% higher in the lenses exposed to UVR compared with the nonexposed lenses. Conclusions: Additivity does not always hold true for UVR-induced cataract. The reciprocity law cannot be applied to UVR-induced cataract for exposures between 5 -120 minutes. Vitamin E protects the lens against UVR induced cataract. The inapplicability of the reciprocity law for shorter periods of time can be attributed to oxidation. Apoptosis in the lens due to UVR exposure may be mediated through increased p53 expression.

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