Dose dependent cataractogenesis and Maximum Tolerable Dose (MTD(2.3:16)) for UVR 300 nm-induced cataract in C57BL/6J mice.
The purpose of the present study was to investigate the in vivo dose response function for UVR 300 nm-induced cataract in the C57BL/6J mouse lens and to establish a cataract threshold estimate expressed as Maximum Tolerable Dose (MTD(2.3:16)) for UVR 300 nm-induced cataract in the C57BL/6J mouse lens. Knowledge of the MTD(2.3:16) 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 8 kJ/m(2) UVR 300 nm for 15 min (n=20). The radiation output of the UVR-source had lambda(max) at 302.6 nm with 5 nm 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. MTD(2.3:16) 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 8 kJ/m(2) UVR 300 nm. Forward light scattering intensity increased with increasing UVR 300 nm dose. MTD(2.3:16) for the mouse lens was estimated to 2.9 kJ/m(2) UVR 300 nm. Lens light scattering intensity in the C57BL/6J mouse lens increases with UVR 300 nm in vivo dose in the range 0-8 kJ/m(2). The MTD(2.3:16) of 2.9 kJ/m(2) 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 300 nm-induced cataract pathogenesis.
Meyer
Linda M
LM
St Erik's Eye Hospital, Karolinska Institutet, Stockholm, Sweden. linda.meyer@ste.ki.se
Dong
Xiuqin
X
Wegener
Alfred
A
Söderberg
Per
P
D000818:Animals; D002386:Cataract / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020714:Maximum Tolerated Dose; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000473:pathology; D012542:Scattering, Radiation; D014466:Ultraviolet Rays / Q000009:adverse effects*