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M. G. Anderson, N. L. Hawes, B. Chang, G. E. Petersen, B. Jiang, G. Lively; Genetic Dissection of Central Corneal Thickness Utilizing Inbred Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3932.
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Central corneal thickness (CCT) varies widely in humans. More than a mere anatomical curiosity, CCT exhibits associations with a variety of ocular diseases, suggesting that the genes regulating CCT are likely to be of broad importance to the eye. Here, we initiate a genetic approach for studying CCT with mice by developing methodology and resources enabling a phenotype-driven approach utilizing inbred strains of mice.
Techniques for non-invasively measuring CCT in mice were developed utilizing a Sonogage Ultrasound Pachymeter. Reliability was tested by comparing pachymeter measurements to direct measurements of unfixed ocular cryosections. Experiments were initially performed with the widely utilized C57BL/6J strain of mice and then applied to a variety of different inbred strains.
In accord with previous studies of CCT in rodents, we measured a CCT of 97.6 +/- 2.7 µm (mean +/- SD) for adult (100 day) C57BL/6J mice. No sex-specific effects were detected. Measurements of CCT did exhibit age-dependency in young mice, but remained relatively constant past 10 weeks of age. Our initial survey of CCT among a diverse set of different inbred mouse strains identified strain-specific and non-overlapping differences in CCT (n=8-10 eyes per strain, 90-120 days). Among these strains, mean CCT varied between a low of 89.0 +/- 6.1 (strain C57BLKS/J) to a high of 123.1 +/- 4.8 µm (strain SJL/J). Histologic comparisons of C57BLKS/J (thin), C57BL/6J (mid), and SJL/J (thick) corneas demonstrates correlations between CCT and stromal thickness, as well as keratocyte density. No other indices of overt pathology were detected, likely indicating that CCT among these strains is a naturally occuring spectrum of wild-type phenotypes and likely a direct consequence of genetic background.
Like human eyes, the eyes of different strains of inbred mice display a significant variability in CCT. Because these strains also have inherent genetic diversity, they represent a powerful resource for genetic linkage studies. We are currently conducting genetic mapping crosses to identify the loci dictating these differences. In our ongoing studies, we intend to continue studying genetic pathways influencing CCT and apply these resources as an experimental system for studying associations between CCT and glaucoma.
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