Abstract
Cataract is the leading cause of blindness in the world. Epidemiological and experimental evidence supports a link between mid-range ultraviolet radiation (UVR-B) exposure and the development of cataract. Globally, there are 20 million people who have become bilaterally blind from cataract, representing 51 % of cases of all causes of blindness due to eye disease. No conservative methods are available to prevent, delay or reverse the development of cataract. The only cure for cataract is cataract surgery. A large number of people need cataract surgery, which results in a burden to the health care system. In 2004, the World Health Organization estimated that the number of cases of cataract would double by the year 2020.
The purpose of this work was to increase our understanding of acute and chronic UVR-B induced cataract development. A novel rat restrainer, a UVR source, a light dissemination meter, macroscopic imaging, light and transmission electron microscopy and quantitative RT-PCR were the methods in this thesis.
A new rat restraining device was developed to immobilize the animal and its head in order to permit a single or repeated well-controlled experimental in vivo exposure to optical radiation without the need for anesthesia (paper I). The newly developed rat restrainer was used in three studies: a study on the evolution of damage in the lens after a single in vivo close-to-threshold exposure to UV-B radiation (paper II), a study of subthreshold repeated in vivo exposures to UV-B radiation (paper III) and a study of GADD45α, TP53 and CASP3 gene expression in the lens exposed to UVR-B (paper IV). In the evolution study, we characterized the chronology of morphological changes in the lens exposed to a close-to-threshold dose of UVR-B and revealed that they correlated with previously reported findings at ten times the threshold. The lens epithelium was the site of the initial UVR-B damage that progressed and subsequently involved the entire lens. Light and transmission electron microscopy revealed that epithelial damage occurred due to apoptosis within 48 hours after exposure, followed by repair at 336 hours. Cortical fiber cells remained damaged at 336 hours following exposure. In the study of subthreshold repeated in vivo exposures to UVR-B, daily exposures accumulated to cause cataract, supporting the epidemiological evidence for the association between solar UVR-B exposure and cortical cataract. An increase in the number of exposure days up to 30 days resulted in an increase in tolerance in the lens expressed as MTD2.3:16. This finding deviates from the current safety guidelines stating that all damage in the lens is repaired within 24 hours. Double the threshold dose of UVR-B induced a transient upregulation of the stress sensor GADD45α and a transient downregulation of the apoptosis markers TP53 and CASP3, followed by a constant upregulation of TP53 that preceded a constant upregulation of CASP3 in the rat lens in vivo.
