Dose dependent cataractogenesis and Maximum Tolerable Dose (MTD2.3:16) for UVR 300 nm-induced cataract in C57BL/6J mice

Abstract

The purpose of the present study was to investigate the in vivo dose response function for UVR 300nm-induced cataract in the C57BL/6J mouse lens and to establish a cataract threshold estimate expressed as Maximum Tolerable Dose (MTD2.3:16) for UVR 300 nm-induced cataract in the C57BL/6J mouse lens. Knowledge of the MTD2.3:16 in the C57BL/6J mouse will permit quantitative in vivo comparison of UVR-B threshold sensitivity of knockout mice, e.g. animals deficient in key antioxidative enzymes or mice suffering from genetically predetermined eye disease, to wild type animals. Eighty C57BL/6J mice were divided into four dose groups. The animals were exposed unilaterally to 0, 2, 4, or 8kJ/m2 UVR 300nm for 15min (n=20). The radiation output of the UVR-source had λmax at 302.6nm with 5nm full width at half maximum. Two days after exposure cataract was quantified as forward lens light scattering intensity in the exposed and the contralateral non-exposed lens. Morphological lens changes were documented using grid and dark field illumination photography. MTD2.3:16 was estimated from the forward light scattering measurements. Two days after exposure mainly anterior subcapsular but also cortical and nuclear cataract developed in lenses that had received 2, 4, and 8kJ/m2 UVR 300nm. Forward light scattering intensity increased with increasing UVR 300nm dose. MTD2.3:16 for the mouse lens was estimated to 2.9kJ/m2 UVR 300nm. Lens light scattering intensity in the C57BL/6J mouse lens increases with UVR 300nm in vivo dose in the range 0–8kJ/m2. The MTD2.3:16 of 2.9kJ/m2 in the C57BL/6J mouse lens determined here, is essential to quantify and compare in vivo the impact of genetic modulation on lens susceptibility to oxidative stress and plan dose-ranges in future investigations of UVR 300nm-induced cataract pathogenesis.