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Norman J Kleiman, Eric Hall, Mike M Weil, Catherine Schmidt, Elijah Edmondson, Adam King; Radiation cataract in an outbred population of mice following gamma or high-LET irradiation.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2509.
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© ARVO (1962-2015); The Authors (2016-present)
This study was designed to determine the influence of genetic background on radiation cataract after either HZE ion or gamma irradiation. Most radiation cataract rodent models utilize inbred strains with limited genetic heterogeneity. The availability of diversity outbred heterogeneous mouse stocks combined with high-throughput single nucleotide polymorphism (SNP) genotyping, facilitates new approaches to study radiation cataract in genetically heterogeneous populations. These tools should permit better analysis of radiation-induced gene-environment interactions and better models the genetic diversity found in human populations.
1,800 HS/Npt 2 month old mice of both sexes were irradiated with 0.4 Gy of 240 MeV/n 28Si, 600 MeV/n 56Fe ions, or 3 Gy 137Cs gamma rays, or sham irradiated controls. As part of a larger study examining carcinogenesis, cognitive deficits or ocular defects, the eyes of mice were monitored by dilated slit lamp exam and their vision by Virtual Optomotry for up to two years of age. Lens opacities were staged by modified Merriam-Focht scoring. Each mouse was also genotyped for 78,000 SNPs.
Radiation of both qualities increased cataract development with Hazard Ratios of ~2.3 for γ and ~2.6 for HZE. HZE irradiated mice are at increased risk over gamma irradiation. Cataract susceptibility loci in these heterogeneous mice are being mapped to determine overlap, if any, with either cognitive or carcinogenic endpoints. The SNP genotype data is being used to localize the genetic factors that predispose individual mice to either spontaneous ocular defects or radiation-induced posterior subcapsular lens changes. Time of onset of lens opacification and final lens opacity severity score demonstrate strong family-specific susceptibility. No gender specific preference for lens opacity was noted.
There are strong family-based genetic determinants that influence predisposition to radiation cataract in an outbred mouse population irradiated with either low- or high-LET radiation. There does not appear to be any gender based predisposition within this cohort. The availability of new analytical tools permits comparison of these findings with genetic loci associated with specific carcinogenic or cognitive endpoints in these same mouse populations.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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