Thesis (Ph.D.)--Aberdeen University, 2008. / Title from web page (viewed on Apr. 20, 2009). Includes bibliographical references.

This work used <i>Pax6</i>^+/- mice as a model for Pax6-realted corneal diseases and assessed the roles of oxidative stress and epithelial injury in the aetiology of ARK. Histological investigation revealed epithelial lesions in <i>Pax</i>6^+/- corneas. Proteomic analysis demonstrated reduced levels of protective enzymes, transketolase, aldehyde dehydrogenase 3A1 and glutathione S-transferase α4, and cytoskeletal proteins. Keratin 5 and 12 in <i>Pax</i>6^+/- adult mouse corneas. These physical/structural and chemical defects imply that <i>Pax</i>6^+/- corneas may be in a chronic ‘stressed and wounded’ state. Using a DNPH/protein oxidation assay, <i>Pax</i>6^+/- corneal protein oxidation was found to be consistently higher than that in <i>wild-type</i> (WT), and to get worse with age, in parallel with the development of corneal opacity. H₂O₂ was used to induce oxidative stress in mouse corneas and this was found to activate the Ca²⁺ (protein kinase C/ phospholipase C) → p38/p42/p44 mitogen activated kinase signalling pathway. Oxidative stress-induced Pax6 exclusion form cell nucleus led to abnormal expression of non-corneal epithelial markers, indicating a metaplasia process that may cause normally transparent epithelial cells to become opaque. This report for the first time describes cytoskeleton architectures <i>in vivo</i> using flat-mount mouse corneal epithelial by fluorescent staining and confocal microscopy, which is potentially applicable to studies interested in cytoskeleton <i>in vivo</i>. Keratin, desmoplakin and actin cytoskeletal structures were found to be heterogeneous and defective in <i>Pax</i>6^+/- cells. Twenty-one hours after wounding WT corneal epithelia <i>in vivo</i>, healing cells developed desmoplakin and actin structural features, intercellular gaps, interdigitated filopodia-like processes and vesicles similar to the unscratched <i>Pax</i>6^+/- corneal epithelia. These data support the hypothesis of a ‘chronic wounded’ state in apparently uninjured <i>Pax</i>6^+/- corneal epithelia and reveal the cytoskeletal origins of poor adhesion and cellular structure.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Surgery, 2000. / Two leaves of errata and addenda pasted into back pages. Bibliography: leaves 174-208.

Thesis (M.D.)--Dept. of Surgery, University of Adelaide, 2001? / Includes bibliography (leaves 191-219).