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The biomechanical properties of the vitreous humor and replication of these properties to develop substitutes for the vitreous humor have rapidly become topics of interest over the last two decades. In particular, the behavior of the vitreous humor as a viscoelastic tissue has been investigated to identify its role in a variety of processes related to biotransport, aging, and age-related pathologies of the vitreoretinal interface. A thorough search and review of peer-reviewed publications discussing the biomechanical properties of the vitreous humor in both human and animal specimens was conducted. Findings on the effects of biomechanics on vitreoretinal pathologies and vitreous biotransport were analyzed and discussed. The pig and rabbit vitreous have been found to be most mechanically similar to the human vitreous. Age-related liquefaction of the vitreous creates two mechanically unique phases, with an overall effect of softening the vitreous. However, the techniques used to acquire this mechanical data are limited by the in vitro testing methods used, and the vitreous humor has been hypothesized to behave differently in vivo due in part to its swelling properties. The impact of liquefaction and subsequent detachment of the vitreous humor from the posterior retinal surface is implicated in a variety of tractional pathologies of the retina and macula. Liquefaction also causes significant changes in the biotransport properties of the eye, allowing for significantly faster movement of molecules compared to the healthy vitreous. Recent developments in computational and ex vivo models of the vitreous humor have helped with understanding its behavior and developing materials capable of replacing it. A better understanding of the biomechanical properties of the vitreous humor and how these relate to its structure will potentially aid in improving clinical metrics for vitreous liquefaction, design of biomimetic vitreous substitutes, and predicting pharmacokinetics for intravitreal drug delivery. [ABSTRACT FROM AUTHOR]

Research on the vitreous humor and development of hydrogel vitreous substitutes have gained a rapid increase in interest within the past two decades. However, the properties of the vitreous humor and vitreous substitutes have yet to be consolidated. In this paper, the mechanical properties of the vitreous humor and hydrogel vitreous substitutes were systematically reviewed. The number of publications on the vitreous humor and vitreous substitutes over the years, as well as their respective testing conditions and testing techniques were analyzed. The mechanical properties of the human vitreous were found to be most similar to the vitreous of pigs and rabbits. The storage and loss moduli of the hydrogel vitreous substitutes developed were found to be orders of magnitude higher in comparison to the native human vitreous. However, the reported modulus for human vitreous, which was most commonly tested in vitro, has been hypothesized to be different in vivo. Future studies should focus on testing the mechanical properties of the vitreous in situ or in vivo. In addition to its mechanical properties, the vitreous humor has other biotransport mechanisms and biochemical functions that establish a redox balance and maintain an oxygen gradient inside the vitreous chamber to protect intraocular tissues from oxidative damage. Biomimetic hydrogel vitreous substitutes have the potential to provide ophthalmologists with additional avenues for treating and controlling vitreoretinal diseases while preventing complications after vitrectomy. Due to the proximity and interconnectedness of the vitreous humor to other ocular tissues, particularly the lens and the retina, more interest has been placed on understanding the properties of the vitreous humor in recent years. A better understanding of the properties of the vitreous humor will aid in improving the design of biomimetic vitreous substitutes and enhancing intravitreal biotransport. [ABSTRACT FROM AUTHOR]

Tissues in the eye are particularly susceptible to oxidative damage due to light exposure. While vitamin C (ascorbic acid) has been noted as a vital antioxidant in the vitreous humor, its physiological concentration (1–2 mM) has been shown to be toxic to retinal and lens epithelial cells in in vitro cell culture. We have explored adding vitamin C to hydrogel vitreous substitutes as a potential therapeutic to prevent oxidative damage to intraocular tissues after vitrectomy. However, vitamin C degrades rapidly even when loaded at high concentrations, limiting its long-term effectiveness. Glutathione, another antioxidant found abundantly in the lens at concentrations of 2–10 mM, was proposed to be used in conjunction with vitamin C. Cell viability and reactive oxygen species activity of human retinal and lens epithelial cells treated with various combinations of vitamin C, glutathione, hydrogen peroxide, and a hydrogel vitreous substitute were determined using CellTiter-Glo luminescent cell viability assay and dichlorofluorescein assay, respectively. The vitamin C remaining in hydrogel vitreous substitute or glutathione-vitamin C solutions was determined using a microplate reader at 265 nm wavelength, compared against standard solutions with known concentrations. Glutathione protected the lens and retinal cells from the negative effect of vitamin C on cell viability and prolonged the antioxidant effect of vitamin C in vitro. While the detected reading of pure vitamin C solution decreased rapidly from 100% to 10% by 3 days, glutathione provided a significant extension to vitamin C stability, with 70% remaining after 14 days when the glutathione was used at physiological concentrations found in the lens (2–10 mM). These results indicate glutathione might be an effective addition to vitamin C in intraocular implants, including potential vitreous substitutes, and warrants additional studies on the effectiveness of the vitamin C – glutathione combination in preventing oxidative stress post-vitrectomy. [ABSTRACT FROM AUTHOR]