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M.K. Gordon, R.A. Hahn, N. Tovar, B.R. Olsen, E. Reichenberger, M.G. Dunn, D.R. Gerecke; Corneas of Transgenic Mice Secreting Reduced Amounts of Type XII Collagen Have Altered Biomechanical Properties . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2997.
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The role of type XII collagen in the cornea is being addressed by using transgenic mice that secrete reduced amounts of this protein. Previously we determined that the corneas of transgenic mice contain about 25% of the normal amount of type XII collagen, and that the collagen fibrils in the stroma are spaced about 30% closer in the transgenic mouse cornea than in the normal mouse cornea. Here we ask whether the biomechanical properties of the transgenic mouse cornea are altered by having reduced levels of type XII collagen.
Mice age 1.75–2 years old were euthanized and used for these experiments. Corneas were dissected from 3 control and 3 transgenic mice. Corneas were soaked in saline and flattened, then 2 pins were inserted perpendicularly and pulled by the grips of an Instron material tester (Model 4201, Canton, MA). The "tension to failure" at a strain rate of 100% per minute was measured, load–deformation curves were constructed, and the data was analyzed to calculate structural properties, such as breaking load, stiffness/compliance, ultimate deformation, and energy required to tear each cornea.
The maximum load force needed to tear transgenic corneas was 25–30% less than aged matched controls, and the distance that transgenic corneas stretched before tearing (i.e., extension at maximum load) was about half the distance normal corneas extended. However, the transgenic corneas were found to be less stiff: they were on average 10% more compliant than control corneas.
The fact that the transgenic corneas are more compliant than normal corneas, but are more easily torn, suggests that collagen XII plays a crucial role in corneal integrity. These mice may represent an animal model for human keratoconus, a condition where the level of type XII collagen has been shown to be reduced (Cheng et al., Curr Eye Res. 22:333–40, 2001).
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