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Dose dependent cataractogenesis and Maximum Tolerable Dose (MTD(2.3:16)) for UVR 300 nm-induced cataract in C57BL/6J mice
St. Erik's Eye Hospital, Karolinska Institutet.
2008 (English)In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 86, no 2, 282-289 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2008. Vol. 86, no 2, 282-289 p.
Keyword [en]
UVR-B, cataract, oxidative stress, dose-response relationship, C57BL/6J mouse, Maximum Tolerable Dose (MTD(2.3:16)), light scattering
National Category
URN: urn:nbn:se:uu:diva-104235DOI: 10.1016/j.exer.2007.10.019PubMedID: 18083164OAI: oai:DiVA.org:uu-104235DiVA: diva2:220268
Available from: 2009-05-30 Created: 2009-05-28 Last updated: 2012-06-01Bibliographically approved

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Söderberg, Per
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