Cataract from ultraviolet radiation in the mouse

Abstract: Cataract is defined as an opacification of the crystalline lens that results in visual impairment, Cataract is the number one cause of blindness in the world and there are currently no strategies to prevent it. Extraction of cataractogenous lenses is the most commonly performed surgical intervention in industrialized countries. The condition has thus major impact on national health care systems and in consequence on the world economy. Exposure to ultraviolet radiation (UVR) induces cataract in humans and animals. Both epidemiological and experimental evidence indicates maximum lens sensitivity to UVR-B wavelengths around 300 nm. Until today, the impact of genetic modulation on the sensitivity of the lens to UVR remains unexplored. Although chromosomal linkage is observed among several mammals, the human and the laboratory mouse genomes are by far the most extensively characterized and compared. This study introduces the C57BL/6 mouse as a model for UVR cataractogenesis and provides basic information on light scattering in the mouse lens. The C57BU6 mouse lens, as a cataract model, offers for the first time the possibility to study the effect of genetic modulation, on altered sensitivity to oxidative stress, using spontaneously mutated, knockout and transgenic mice. Presently, we characterized light scattering level and variation in the healthy C57BL/6 mouse lens. A tolerance limit for non-pathological light scattering in the mouse lens was defined. We determined natural light scattering variability and estimated required sample sizes for different experimental designs at desired precisions. In the second study, the time evolution of light scattering in the C57BL/6 mouse lens after in vivo exposure to UVR-B was investigated. We demonstrated that a dose of 5 kJ/m2 UVR-B 300 nm induces light scattering in the mouse lens. In vivo exposure to UVR-B induces anterior subcapsular cataract and occasionally cortical and nuclear cataract 1-8 days after exposure to UVR. Light scattering transiently peaks 48 hours after exposure in exposed as well as non-exposed lenses. The third part of this study investigates the dose response function for forward light scattering in the C57BL/6 mouse lens after in vivo exposure to UVR-B 300 rim. Additionally, we established Maximum Tolerable Dose (MTD) as threshold dose for UVR-B induced cataract in the mouse lens. We conclude that the C57BL/6 mouse is a suitable animal to study experimentally induced cataract quantified as forward lens light scattering. Efficient study design is possible based on reasonable sample sizes. Similar to other species, the C57BU6 mouse lens is sensitive to UVR-B-300nm. The finding that cortical and nuclear cataract was identified in addition to anterior subcapsular cataract may indicate a considerable variation in sensitivity to oxidative stress in the mouse lens. Variation of light scattering observed over the time interval studied, resembles a dynamic cataract development following unilateral in vivo exposure to 5 kJ/m2 UVR-B-300 rim. Forward light scattering in the C57BL/6 mouse lens increases continuously with increasing UVR-B dose between 2 and 9 kJ/m2. Unilateral in vivo exposure to UVR-B 300nm might trigger a sympathetic response also in the contralateral, unexposed eye.