Abstract
Purpose :
Altered remodeling processes in the sclera are believed to change scleral biomechanics and contribute to the increased axial length underlying human myopia; however, it is unclear if similar changes occur in the mouse model of myopia. Here, we test the hypothesis that development of form-deprivation myopia (FDM) leads to altered biomechanics (decreased tensile stiffness) in the mouse sclera using unconfined compression mechanical testing.
Methods :
Monocular FDM was induced in naïve, male C57BL/6J mice (n=3) by surgically head-mounting diffuser lenses in front of the right eyes at 4 weeks of age. Refractive power of each eye was measured using a custom autophotorefractor at baseline and ~3 weeks after surgery. Eyes were enucleated immediately after sacrifice and stored in PBS until mechanical testing.
1mm diameter punches were taken from the posterior sclera. Samples were tested under compression using a 3-step stress relaxation protocol. With each step, an additional 5% compressive strain was applied and held until stress equilibrated. A biphasic material model was fit to stress/strain data from each step to determine tensile stiffness and permeability. Two-way repeated measures ANOVAs and Tukey post-hoc comparisons were used to test for significance.
Results :
Mice had a myopic shift of -4.18 ± 1.6 diopters (OD-OS, mean ± stdev.). There was a significant interaction between myopia and strain step (p=0.002), reflected in the increased difference in stiffness between the two groups at step 3 (p<0.001). In all animals and at every step, the myopic sclera was less stiff than its contralateral control (Figure), reflected in a significant main effect of myopia (p<0.001). Further, myopia significantly increased the permeability of scleral samples (p<0.001).
Conclusions :
Murine sclera displayed decreased tensile stiffness and increased permeability in response to FDM. Decreased stiffness is a common feature of mammalian myopia but was not previously confirmed in mice. The effect of myopia on scleral permeability has not been previously evaluated; however, in humans and tree shrews, myopia has been linked to a decrease in glycosaminoglycans, molecules that directly affect tissue permeability. Together, these results suggest a similar scleral remodeling pathway underlies murine myopia as in other mammals. Future work will use transgenic mice to probe potential molecules, such as proteoglycans and proteases, to better elucidate these pathways.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.