Purpose:
To investigate if the posterior scleral biomechanical properties are altered in Beagle dogs affected by the ADAMTS10 mutation [Kuchtey et al, PLoS Genetics, 2011, 7(2)] that leads to naturally occurring primary open angle glaucoma.
Methods:
Beagle dogs of 5-7 month old were genotyped for the ADAMTS10 mutation using DNA sequencing. Scleral strips temporal to the optic nerve head were collected from one eye of each affected (n=4) and age-matched carrier (n=4) dogs, and tested using dynamic and quasi-static protocols. Dynamic mechanical analysis (DMA) was conducted with a 0.15% sinusoidal strain superimposed upon pre-loads of 0.04N and 0.1N at frequencies between 0.1 and 10.0Hz. Complex modulus, tan(Δ), and dynamic viscosity were calculated using the linear theory of viscoelasticity. Following DMA, a tensile ramp was performed at a strain rate of 0.1%/s. The stress-strain curve was fit to an exponential model: σ=A(eBε-1). The quasi-static properties were compared using 2-sample t-tests and the dynamic properties were compared using linear mixed models for repeated measurements at different pre-loads and frequencies.
Results:
The initial elastic modulus (A*B) was 0.25+0.18 MPa in the carriers and 0.56+0.55 MPa in the affected (p=0.32). The B value was 130.6+6.7 in the carriers and 78.5+30.4 in the affected (p=0.02). The dynamic properties were significantly influenced by pre-load and frequency (Fig.1). Complex modulus, tan(Δ), and dynamic viscosity were significantly different between the genotypes (p<0.001), and the differences were consistent at different pre-loads and frequencies.
Conclusions:
Although limited by a small sample size, this study showed a significantly lower B value, complex modulus, tan(Δ), and dynamic viscosity in the posterior sclera of the affected dogs. These results suggested altered posterior scleral biomechanics in Beagle dogs with the ADAMTS10 mutation, which may be linked to the suspected influences of this gene on the extracellular matrix of the sclera. Further studies are needed to elucidate the involvement of scleral biomechanics in glaucoma risk and development.
Keywords: sclera • extracellular matrix • genetics