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Ying-Bo Shui, Benjamen A Filas, Carla J Siegfried, Qianru Zhang, Nan Ma, Alyssa Panitch, David C Beebe; Synthetic Proteoglycan Mimics Preserve Vitreous Structure and Function and in Vivo. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5109. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The vitreous is a non-regenerative tissue that undergoes slow liquefaction with age. Currently, causes for vitreous degeneration are not well understood and there is no treatment for vitreous degeneration, except removal of the vitreous gel (vitrectomy) and replacement with saline solution. The goal of this study is to investigate a potential novel therapy to delay vitreous degeneration or preserve the structure of the vitreous gel, thereby reducing the chance of damage to the retina and lens caused by vitreous degeneration.
The major structural molecules of the vitreous gel are type II collagen and hyaluronic acid. We designed three synthetic proteoglycan mimics (SPM) that specifically bind to type II collagen and /or hyaluronic acid. First, we developed the enzymatically-degraded vitreous degeneration model in vitro and tested how each SPM reacted with fresh bovine vitreous. Shear rheometer was used to test the viscoelastic stiffness of the vitreous. Analysis of morphological changes in vitreous ultrastructure was performed using the novel imaging technique of deep-etch electron microscopy (DEEM). 18 adult albino rabbits were used for injection of the SPM to evaluate toxicity and stability as compared to BSS control in the fellow eye. In vivo observations included slit lamp, intraocular pressure and the ISO (International Organization for Standardization) inflammation score. Retinal histological examinations were also performed.
In vitro studies show that trypsin treatment of bovine vitreous significantly reduced viscoelastic stiffness and increased liquefaction. Addition of SPM to this trypsin-treated vitreous preserved viscoelastic stiffness and liquefaction at similar levels to control vitreous. DEEM analysis showed preservation of vitreous structure by SPM without formation of fiber bundles. In vivo studies in rabbit eyes confirmed the safety of SPM injections. Histological study showed no changes in retinal morphology. Shear rheometry data indicated that the SPM could maintain normal values of viscoelastic stiffness for at least one month in vivo.
This study provides a novel approach to safely preserve the vitreous structure and physical properties of protease-degraded vitreous. Potential utilization of SPMs to prevent age-related vitreous degeneration requires further study.
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