This project focussed on a protein called tear lipocalin that is believed to interact with the lipid layer of the tears and to promote tear film stability. By modulating this protein, it was proposed that tear film stability could be increased, hence the modulation of lipocalin was suggested as a goal for dry eye therapy. The effects on tear lipocalin expression of two potential therapies for dry eye, pharmacological stimulation with phosphodiesterase inhibitors and hormonal regulation with aldosterone and oestrogen HRT were investigated. Initially a rabbit model was employed and the rabbit tear protein profile was characterised. Stimulation of rabbit secretion using phosphodiesterase compounds did not alter rabbit tear lipocalin secretion. Clinical trial of phosphodiesterase compounds in humans did not alter tear lipocalin expression but variation in tear lipocalin isoform expression was noted and new isoforms of tear lipocalin were identified. The steroid hormone aldosterone appeared to modulate rabbit lipocalin and low MW protein expression. A clinical trial to examine the effect of gender, menopause and oestrogen hormone replacement therapy (HRT) on lipocalin secretion demonstrated that oestrogen HRT down regulated lipocalin secretion, increased the thickness of the lipid layer and improved symptomatology compared to the untreated menopause group. High levels of tear lipcalin in the menopause group were associated with symptoms of ocular burning, suggesting that increasing tear lipocalin levels might aggravate the ocular symptoms associated with dry eye. In this thesis it was demonstrated that tear lipocalin secretion was modulated by steroid hormones, but did not appear to be modulated by phosphodiesterase inhibitors. Variation in tear lipocalin concentration did not correlate with measures of tear film stability and indeed, high levels of tear lipocalin may be deleterious for dry eye symptoms. Further analysis of tear a stimulants and hormones will lead to better understanding of tear regulation and will open avenues for dry eye therapy. The application of proteomic tools to tear film will advance our understanding of tear film composition and the role each component in tear film stability. / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:ADTP/234746 |
| Date | January 2001 |
| Creators | Evans, Victoria E., University of Western Sydney, College of Science, Technology and Environment, School of Science |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Source | THESIS_CSTE_SS_Evans_V.xml |
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