Engineering the Mechanical Properties of Ocular Tissues

Citation

Nickerson, Charles Sellers (2006) Engineering the Mechanical Properties of Ocular Tissues. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/0R13-2109. https://resolver.caltech.edu/CaltechETD:etd-03172005-145045

Abstract

Age and disease can cause changes in the mechanical properties of ocular tissues, which compromise visual acuity and can lead to blindness. Thus, there is great interest in understanding the mechanical properties of ocular tissues and in developing appropriate therapeutic strategies. The goal of this thesis is to discover and manipulate the molecular mechanisms that determine the bulk physical properties of the vitreous and the cornea. Both tissues are ordered biocomposites of fibrous collagen embedded in soft matrices of proteoglycans (PGs) and glycosaminoglycans (GAGs). The hydration state, mole fraction, and organization of these components determine the mechanical properties of their respective tissues. We describe the use of a novel "cleat geometry" for rheometry in shear to quantitatively measure the rheological properties of vitreous and other soft biomaterials. Where as the mechanical strength of these tissues has traditionally been attributed to their collagenous components, results from coordinated mechanical and biochemical analyses suggest that PGs and GAGs also make significant contributions. We hypothesize that hyaluronan contributes to the mechanical properties of the vitreous through a Donnan swelling mechanism that induces a state of tension in the collagen network. We hypothesize that the PG/GAG matrix plays a significant role in the mechanics of the cornea by restricting the translation and deformation of the collagen fibrils.

Our therapeutic goal in the vitreous is liquefaction: we seek pharmacological agents capable of separating the vitreous from the retina and destabilizing the network without damaging the adjacent tissues (retina and lens). We present evidence that using urea to disrupt hydrogen bonds may provide clinical benefits by inducing posterior vitreous detachment and reducing the shear modulus of the vitreous.

Our therapeutic goal in the cornea is to stabilize its mechanical properties against the softening associated with keratoconus. We report a clinically-relevant rise in the modulus of corneas treated with glyceraldehyde to induce crosslinking through glycation. We hypothesize that the mechanically-relevant crosslinks are those that change the properties of the soft PG/GAG matrix and its coupling to the collagen fibrils, rather than the much more numerous crosslinks that form within fibrils.

Thesis Files