Quantitative imaging of enzymatic vitreolysis-induced fiber remodeling

• Published in: Investigative ophthalmology & visual science 2014-12, Vol.55 (12), p.8626-8637
• Main Authors: Filas, Benjamen A, Shah, Nihar S, Zhang, Qianru, Shui, Ying-Bo, Lake, Spencer P, Beebe, David C
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Cattle; Disease Models, Animal; Fibrillar Collagens - drug effects; Fibrillar Collagens - ultrastructure; Fibrinolysin - pharmacology; Fibrinolytic Agents - pharmacology; Humans; Microscopy, Electron - methods; Microscopy, Polarization - methods; Proteoglycans - physiology; Retinal Diseases - pathology; Swine; Trypsin - pharmacology; Ultrasonography; Vitreous Body - diagnostic imaging; Vitreous Body - drug effects
• ISSN: 0146-0404; 1552-5783
• DOI: 10.1167/iovs.14-15225

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. 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. 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). 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.