Structure and mechanics of the vitreoretinal interface
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.
Section snippets
Vitreous
The vitreous occupies 80% of the ocular volume, making it the largest structure in the eye (Sebag, 1998). The vitreous is between 98 and 99.7% water with a three-dimensional network of heterotypic collagen fibrils maintaining the gel-like structure (Bishop, 1996). These fibrils are randomly spaced and held apart by hyaluronan, otherwise known as hyaluronic acid (HA). HA is a glycosaminoglycan (GAG) that is hydrophilic and acts to inflate the vitreous, providing resistance to compression. The
Posterior vitreous detachment (PVD)
With age, the vitreous gel begins to liquefy and separate from the retina. Vitreous liquefaction first appears in human eyes as early as four years of age (Balazs and Denlinger, 1982). At least half of the vitreous is liquefied in most people over 70 years of age. Accelerated vitreous liquefaction may lead to adverse outcomes, and may occur in people with myopia (Stirpe and Heimann, 1996), aphakia (Harocopos et al., 2004), intraocular inflammation (Hogan, 1975), retinal vein occlusion (Ma et
Experimental measurement of vitreoretinal adhesion
Very little data has been collected to measure the strength of adhesion in different regions of the eye and at different ages. Sebag (1991) peeled the retina from the ILM in the vitreous base and posterior pole in 59 human eyes (ages 33 weeks gestation to 94 years of age) using forceps. After peeling, retina samples were evaluated using TEM to visualize the failure and estimate strength. In the posterior pole, all eyes from individuals 21 years of age and older failed cleanly between the ILM
Potential mechanisms of vitreoretinal adhesion
The above experimental and computational studies illustrate age- and region-specific differences in vitreoretinal adhesion and failure. However, the precise mechanisms of adhesion at the VRI remain unclear. Several possibilities emerge when considering the biochemistry of the interface and adhesion mechanisms in other tissues. Interfacial adhesion in biological tissues is achieved mainly through complex networks of fibrous proteins, elastin, fibronectin, laminins, glycoproteins, proteoglycans,
Conclusion and future studies
From the available experimental data, we conclude that mechanisms of vitreoretinal adhesion are region-dependent. The primary adhesion mechanisms in the posterior pole appear to be different from those in the equator and vitreous base. It is likely that the macula also has a unique adhesion mechanism, but there is no data to date to verify this statement or suggest what that mechanism may be. The specific region-dependent adhesion mechanisms need to be clarified to understand the regional
CRediT authorship contribution statement
Joseph D. Phillips: Writing – review & editing, Writing – original draft. Eileen S. Hwang: Writing – review & editing. Denise J. Morgan: Writing – review & editing. Christopher J. Creveling: Investigation. Brittany Coats: Writing – review & editing, Writing – original draft.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
Research reported in this review was supported by the National Eye Institute of the US National Institutes of Health under award number EY025813. The authors would like to acknowledge the Utah Lions Eye Bank for human tissue donation and the Dr. Kurt Albertine Lab for sheep eye donation. Electron microscopy was performed by C.J. Creveling at the University of Utah Electron Microscopy Core Laboratory. Financial support for authors E. Hwang and D. Morgan during generation of this review article
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