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Title: A model of ageing vitreous : implications for drug delivery
Author: Tan, Lay Ean
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2010
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This thesis concerns the development of ex-vivo and in vivo models of vitreous synchisis, a condition that develops in the elderly. The biophysical properties of the vitreous and the effects of liquefaction on the ocular disposition of intravitreally injected substances were investigated. Conventional rheometry demonstrated that the vitreous is a non-uniform, lightly cross-linked viscoelastic solid gel, which, once destroyed, cannot be re-formed. Optical trapping was used to quantify the local viscosity with the objective of allowing repeat measurements in the same sample, a method validated using methylcellulose solutions. The technique was used to quantify viscosity changes induced by a freeze-thaw cycle, with the thawed samples having lower viscosity and more sample variables. The vitreous microstructure was imaged using a blue LED and fluorescent microparticle suspension within the Miyake-Apple eye preparations. The microstructure was shown to be a barrier to particle moveme nts, and its failure to reanneal following injection, led to reflux along the needle track. In this model, intravitreal flow processes were found important in facilitating subsequent particle movement within the vitreous cavity. By using hyaluronidase to destroy the vitreous hyaluronan, a model with ~50% vitreous liquefaction was developed in Dutch-belted rabbits. Following intravitreal injection, the distribution of sodium fluorescein and fluorescein isothiocyanate dextran was greater in the liquefied vitreous than in controls. Intravitreally injected fluorescent particles were found to sediment faster in the liquefied vitreous with a more dispersed and scattered distribution. Studies on the pharmacokinetics of the a2-adrenergic agonist brimonidine administered either as a single bolus injection or a controlled-release implant, revealed that vitreous liquefaction affected the disposition of brimonidine to a greater effect following intravitreal injection than intravitreal implantation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available