The Roles of Vitreous Biomechanics in Ocular Disease, Biomolecule Transport, and Pharmacokinetics

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords:

• Vitreous humor
• biomechanics
• biotransport
• aging
• vitreous liquefaction
• viscoelasticity
• ex vivo modeling
• intravitreal transport
• drug diffusion
• vitreous swelling

Acknowledgements

Wade Rich provided eyes for dissection and provided insight into understanding the vitreous humor.

Disclosure statement

Nguyen K. Tram and Matthew A. Reilly have patent applications for vitreous substitutes. Katelyn E. Swindle-Reilly has patent applications for ocular drug delivery technologies and vitreous substitutes. Katelyn E. Swindle-Reilly consults for and has equity interest in Vitranu, Inc. who has licensed ocular drug delivery and vitreous substitute technologies from her lab.

Data availability statement

All data supporting the findings of this study are available from the corresponding author, Katelyn E. Swindle-Reilly, upon request.

Additional information

Funding

We would like to acknowledge The Ohio State University College of Engineering and The Ohio Lions Eye Research Foundation for funding.