title: Quantitative imaging of enzymatic vitreolysis-induced fiber remodeling.
abstract: OBJECTIVE
  Collagen fiber remodeling in the vitreous body has been implicated in cases of vitreomacular traction, macular hole, and retinal detachment, and also may occur during pharmacologic vitreolysis. The purpose of this study was to evaluate quantitative polarized light imaging (QPLI) as a tool for studying fiber organization in the vitreous and near the vitreoretinal interface in control and enzymatically perturbed conditions.
  
  
  METHODS
  Fiber alignment was measured in anterior-posterior sections of bovine and porcine vitreous. Additional tests were performed on bovine lenses and nasal-temporal vitreous sections. Effects of proteoglycan degradation on collagen fiber alignment using trypsin and plasmin were assessed at the microstructural level using electron microscopy and at the global level using QPLI.
  
  
  RESULTS
  Control vitreous showed fiber organization patterns consistent with the literature across multiple-length scales, including the global anterior-posterior coursing of vitreous fibers, as well as local fibers parallel to the equatorial vitreoretinal interface and transverse to the posterior interface. Proteoglycan digestion with trypsin or plasmin significantly increased fiber alignment throughout the vitreous (P < 0.01). The largest changes (3×) occurred in the posterior vitreous where fibers are aligned transverse to the posterior vitreoretinal interface (P < 0.01).
  
  
  CONCLUSIONS
  Proteoglycan loss due to enzymatic vitreolysis differentially increases fiber alignment at locations where tractions are most common. We hypothesize that a similar mechanism leads to retinal complications during age-related vitreous degeneration. Structural changes to the entire vitreous body (as opposed to the vitreoretinal interface alone) should be evaluated during preclinical testing of pharmacological vitreolysis candidates.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
authors.forename: Benjamen A
authors.initials: BA
authors.lastname: Filas
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
authors.forename: Nihar S
authors.initials: NS
authors.lastname: Shah
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States Eye Center, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qianru
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
authors.forename: Ying-Bo
authors.initials: YB
authors.lastname: Shui
authors.affiliation: Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, Missouri, United States.
authors.forename: Spencer P
authors.initials: SP
authors.lastname: Lake
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Beebe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D024022:Fibrillar Collagens / Q000187:drug effects / Q000648:ultrastructure*; D005341:Fibrinolysin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron / Q000379:methods; D008859:Microscopy, Polarization / Q000379:methods; D011509:Proteoglycans / Q000502:physiology; D012164:Retinal Diseases / Q000473:pathology*; D013552:Swine; D014357:Trypsin / Q000494:pharmacology; D014463:Ultrasonography; D014822:Vitreous Body / Q000000981:diagnostic imaging* / Q000187:drug effects
chemical_list: D024022:Fibrillar Collagens; D005343:Fibrinolytic Agents; D011509:Proteoglycans; D014357:Trypsin; D005341:Fibrinolysin
keywords: collagen; plasmin; polarized light imaging; proteoglycans; trypsin; vitreoretinal traction; vitreous; vitreous degeneration