Qianru Zhang1, Benjamen A Filas2, Robyn Roth3, John Heuser3, Nan Ma4, Shaili Sharma5, Alyssa Panitch5, David C Beebe6, Ying-Bo Shui2. 1. Eye Center, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States. 2. Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States. 3. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States. 4. Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. 5. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States. 6. Department of Ophthalmology & 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.
Abstract
PURPOSE: Vitreous liquefaction and subsequent posterior vitreous detachment can lead to several sight-threatening diseases, including retinal detachment, macular hole and macular traction syndrome, nuclear cataracts, and possibly, open-angle glaucoma. In this study, we tested the ability of three novel synthetic chondroitin sulfate proteoglycan mimics to preserve the structure and physical properties of enzymatically-degraded bovine vitreous. METHODS: Chondroitin sulfate proteoglycan mimics, designed to bind to type II collagen, hyaluronic acid, or both, were applied to trypsin- or collagenase-treated bovine vitreous in situ and in vitro. Rheology and liquefaction tests were performed to determine the physical properties of the vitreous, while Western blots were used to detect the presence and degradation of soluble collagen II (α1). Deep-etch electron microscopy (DEEM) identified the ultrastructure of mimic-treated and untreated enzyme-degraded bovine vitreous. RESULTS: Proteoglycan mimics preserved the physical properties of trypsin-degraded bovine vitreous and protected against vitreous liquefaction. Although the collagen-binding mimic maintained the physical properties of collagenase-treated vitreous, liquefaction still occurred. Western blots indicated that the mimic provided only marginal protective ability against soluble collagen degradation. Deep-etch electron microscopy, however, showed increased density and isotropy of microstructural components in mimic-treated vitreous, supporting the initial result that vitreous structure was preserved. CONCLUSIONS: Proteoglycan mimics preserved bovine vitreous physical properties after enzymatic degradation. These compounds may be useful in delaying or preventing the pathological effects of age-related, or enzymatically-induced, degradation of the vitreous body. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: Vitreous liquefaction and subsequent posterior vitreous detachment can lead to several sight-threatening diseases, including retinal detachment, macular hole and macular traction syndrome, nuclear cataracts, and possibly, open-angle glaucoma. In this study, we tested the ability of three novel synthetic chondroitin sulfate proteoglycan mimics to preserve the structure and physical properties of enzymatically-degraded bovine vitreous. METHODS:Chondroitin sulfate proteoglycan mimics, designed to bind to type II collagen, hyaluronic acid, or both, were applied to trypsin- or collagenase-treated bovine vitreous in situ and in vitro. Rheology and liquefaction tests were performed to determine the physical properties of the vitreous, while Western blots were used to detect the presence and degradation of soluble collagen II (α1). Deep-etch electron microscopy (DEEM) identified the ultrastructure of mimic-treated and untreated enzyme-degraded bovine vitreous. RESULTS: Proteoglycan mimics preserved the physical properties of trypsin-degraded bovine vitreous and protected against vitreous liquefaction. Although the collagen-binding mimic maintained the physical properties of collagenase-treated vitreous, liquefaction still occurred. Western blots indicated that the mimic provided only marginal protective ability against soluble collagen degradation. Deep-etch electron microscopy, however, showed increased density and isotropy of microstructural components in mimic-treated vitreous, supporting the initial result that vitreous structure was preserved. CONCLUSIONS: Proteoglycan mimics preserved bovine vitreous physical properties after enzymatic degradation. These compounds may be useful in delaying or preventing the pathological effects of age-related, or enzymatically-induced, degradation of the vitreous body. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
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