Changes in posterior scleral collagen microstructure in canine eyes with an ADAMTS10 mutation

PURPOSE: We aimed to characterize alterations in the posterior scleral collagen microstructure before detectable disease onset in a canine model of open-angle glaucoma caused by an ADAMTS10 mutation. METHODS: Collagen orientation, anisotropy degree (proportion of preferentially aligned collagen), and relative density were measured at 0.4 mm spatial resolution using synchrotron wide-angle X-ray scattering. For statistical evaluation of structure parameters, regional averages of the peripapillary and mid-posterior sclera were compared between ADAMTS10 mutant (affected) dogs (n = 3) and age-matched (carrier) controls (n = 3). RESULTS: No marked differences in the general pattern of preferential collagen fibril orientation were noted between the control and affected dogs. The peripapillary sclera of all specimens featured strongly aligned circumferential collagen ringing the optic nerve head. Collagen anisotropy was significantly reduced in the mid-posterior sclera of the affected dogs (carrier: 0.27±0.11; affected: 0.24±0.10; p = 0.032) but was not statistically significantly different in the peripapillary sclera (carrier: 0.46±0.15; affected: 0.45±0.17; p = 0.68). Collagen density was statistically significantly reduced in the affected dogs for the mid-posterior sclera (carrier: 28.1±9.14; affected: 18.3±5.12; p<0.0001) and the peripapillary sclera (carrier: 34.6±9.34; affected: 21.1±6.97; p = 0.0002). CONCLUSIONS: Significant alterations in the posterior scleral collagen microstructure are present before the onset of clinical glaucoma in ADAMTS10 mutant dogs. A reduction in fibrous collagen density is likely an important contributory factor in the previously reported mechanical weakening of the sclera in this model. Baseline scleral abnormalities have the potential to interact with intraocular pressure (IOP) elevations in determining the course of glaucoma progression in animal models of the disease, and potentially in human glaucoma.