title: Changes in posterior scleral collagen microstructure in canine eyes with an ADAMTS10 mutation.
abstract: OBJECTIVE
  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.
authors.affiliation: Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Boote
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, OH.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Palko
authors.affiliation: Diamond Light Source, Harwell Science and Innovation Campus, Harwell, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sorensen
authors.affiliation: School of Engineering, University of Liverpool, Liverpool, UK.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Mohammadvali
authors.affiliation: School of Engineering, University of Liverpool, Liverpool, UK; NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elsheikh
authors.affiliation: Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI; Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: András M
authors.initials: AM
authors.lastname: Komáromy
authors.affiliation: Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, OH.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000818:Animals; D016880:Anisotropy; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D007429:Intraocular Pressure; D008297:Male; D009154:Mutation; D012590:Sclera / Q000378:metabolism / Q000473:pathology*; D014961:X-Ray Diffraction
chemical_list: D003094:Collagen; D051722:ADAM Proteins