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Dillon Brown, C Ross Ethier, Machelle Pardue; Altered Scleral Biomechanics Accompany Early Myopia Development in Mice. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3410.
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© ARVO (1962-2015); The Authors (2016-present)
The sclera is believed to biomechanically regulate eye size and play a key role in facilitating excessive axial elongation in myopia, supported by evidence of rapidly altered scleral proteoglycans and tensile creep behavior in eyes subjected to myopigenic stimuli. Here, we test the hypothesis that both altered scleral tensile stiffness and permeability accompany early myopia development in the mouse model of form-deprivation myopia (FDM).
FDM was initiated at P28 in 13 C57BL/6J mice by applying diffuser lenses unilaterally OD, leaving contralateral eyes as controls. Lens compliance was maintained for 1 (n=7) or 3 weeks (n=6). Refractive error (RE) and axial length (AL) were measured at baseline and the day of sacrifice. Eyes were enucleated and sclerae isolated for biomechanical quantification of tensile stiffness (E) and hydraulic permeability (k) using unconfined compression and a biphasic material model.
A significant myopic shift (RE OD-OS) was measured at 1 week (-2.4±0.9D, p<0.001) that further increased after 3 weeks treatment (-3.7±0.4D, p=0.025). There was no measurable change in AL at either 1 or 3 weeks. FDM significantly affected scleral biomechanics (main effect: FDM; E: F(2,45)=4.99, p=0.017; k: F(2,45)=3.61, p=0.043). At 1 week, mouse sclerae stiffness was decreased by 19.4 ± 21.5% compared to contralateral eyes (p=0.005). After 3 weeks of FDM, sclerae were 31.4 ± 12.7% less stiff (p<0.001). After 1 week of FDM, sclerae were 137±146% more permeable than contralateral sclerae (p=0.002) and 224.4 ± 205.5% more permeable after 3 weeks (p<0.001). Both biomechanical parameters did not significantly change from 1 to 3 weeks.
Mice developed a myopic RE after 1 week of treatment, accompanied by stark differences in the permeability and stiffness of the sclera. While the magnitude of the myopic shift increased at 3 weeks, neither permeability nor stiffness changed further. It is possible that myopia continued to progress independently of further changes in scleral biomechanics or that the current methods did not have the sensitivity to detect changes in the small and thin mouse sclera. The strong and early change in permeability of myopic mouse sclera warrants further research into changes in proteoglycans that may contribute to altered biomechanics.
This is a 2020 ARVO Annual Meeting abstract.
Figure 1: Effect of 1 and 3 weeks of form deprivation on refraction, stiffness (E), and permeability (k).
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