Structure and mechanics of the vitreoretinal interface

Abstract

Vitreoretinal mechanics plays an important role in retinal trauma and many sight-threatening diseases. In age-related pathologies, such as posterior vitreous detachment and vitreomacular traction, lingering vitreoretinal adhesions can lead to macular holes, epiretinal membranes, retinal tears and detachment. In age-related macular degeneration, vitreoretinal traction has been implicated in the acceleration of the disease due to the stimulation of vascular growth factors. Despite this strong mechanobiological influence on trauma and disease in the eye, fundamental understanding of the mechanics at the vitreoretinal interface is limited. Clarification of adhesion mechanisms and the role of vitreoretinal mechanics in healthy eyes and disease is necessary to develop innovative treatments for these pathologies. In this review, we evaluate the existing literature on the structure and function of the vitreoretinal interface to gain insight into age- and region-dependent mechanisms of vitreoretinal adhesion. We explore the role of vitreoretinal adhesion in ocular pathologies to identify knowledge gaps and future research areas. Finally, we recommend future mechanics-based studies to address the critical needs in the field, increase fundamental understanding of vitreoretinal mechanisms and disease, and inform disease treatments.

Introduction

The mechanics of adhesion at the vitreoretinal interface (VRI) contribute to the progression of many diseases that lead to visual impairment or blindness. For example, strong focal vitreoretinal adhesions can prevent complete posterior vitreous detachment (PVD) from occurring. These adhesions can exert traction forces on the retina, leading to macular holes and epiretinal membranes in the macula, and retinal tears and detachment in the periphery (Escoffery et al., 1976; Jackson et al., 2013; Patronas et al., 2009). In age-related macular degeneration (AMD), persistent focal attachments between the vitreous cortex and the macula are more prevalent in exudative AMD than non-exudative AMD (Jackson et al., 2013; Krebs et al., 2007) and may be an important risk factor for the disease.

Despite its involvement in these debilitating visual diseases, the mechanisms and mechanics of vitreoretinal adhesion are not well understood. The protein composition at the VRI has been investigated (Jerdan et al., 1989; Kohno et al., 1987; Russell et al., 1991), but has not been explicitly linked to the mechanics of the VRI. Further, vitreoretinal adhesion has not been directly measured until very recently (Creveling et al., 2018). There is a critical need for research focused on elucidating the mechanics of the VRI to address these limitations. Such research could identify region-dependent multiscale mechanisms across the VRI and evaluate how those mechanisms change or weaken with age. The strength of adhesion could be connected to the microstructure and offer insight into the best methodology to eliminate adhesion without compromising the underlying architecture of the retina. Further, a better understanding of the adhesion mechanisms could lead to imaging biomarkers to identify those at risk for lingering vitreoretinal adhesion.

In this review, we prepare for the development of this new field of research by evaluating existing literature on the VRI from the perspective of mechanics. We first evaluate the well-characterized microstructure and composition of the VRI and identify how each component contributes to structural integrity and mechanical adhesive strength. Then, we discuss the many pathologies affected by vitreoretinal adhesion and identify areas where knowledge of adhesion mechanics could accelerate the discovery of treatments for those diseases. Next, we explore microstructural mechanisms of adhesion in non-ocular biological tissues to identify potential mechanisms of adhesion at the VRI in light of existing experimental VRI data. Finally, we end the review with a discussion of the critical needs in the field and recommend future mechanics-based studies to address those needs.