Engineering the mechanical properties of ocular tissues

The mechanical properties of the structural tissues of the eye (cornea, sclera, and vitreous) are critical for vision. Age and disease can cause changes in their physical properties and compromise visual acuity; in the extreme, such changes 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. These tissues are both ordered biocomposites of fibrous collagen embedded in soft matrices of proteoglycans and glycosaminoglycans (GAGs). The hydration state, mole fraction, and particularly the organization of these components determine the mechanical properties of the respective tissues. Whereas the mechanical strength of these tissues has traditionally been attributed to their collagenous components, we present evidence that the PGs and GAGs also make significant contributions. We also suggest hypotheses regarding the mechanisms by which the carbohydrate components contribute and how they can be utilized for therapeutic purposes.;In order to study the unique physical properties of the vitreous, novel instrumentation was developed. We describe the use of cleated surfaces on parallel disk tools to quantitatively measure the rheological properties of diverse slip-prone fluids and soft materials. Densely-packed protrusions (0.45mm x 0.45mm cross section x 0.6mm length, 0.9mm apart) penetrate the slip layer, preventing significant flow between cleats. This creates a no-slip boundary ∼0.16mm below their tips, which serves as the sample gap boundary, in direct analogy to the parallel plate geometry. This "cleat" geometry suppresses slip without application of significant normal force, it imposes well-defined shear to enable absolute measurements, and is compatible with small sample volumes. The geometry was validated and oscillatory shear using a series of materials not prone to slip (Newtonian oils and an entangled polymer melt). The advantage of cleated tools over other slip-prevention methods was demonstrated using slip-prone materials, including an emulsion, a suspension, and porcine vitreous humor. (Abstract shortened by UMI.).