Pterygium is an ocular surface disorder characterised by centripetal invasion of the cornea by altered limbal cells, accompanied by fibrosis and neovascularisation. One of the enigmatic features of pterygium is its wing-like shape and the mechanism(s) supporting its centripetal growth remain to be elucidated. As the growth pattern of pterygia mirrors the radial arrangement of corneal nerves, we hypothesised that neuropeptides may facilitate its directional growth. In this thesis, we investigated the roles that the sensory neuropeptide substance P (SP) may play in the pathogenesis of pterygia given its known functions in corneal cell migration, proliferation, wound healing and neurogenic inflammation. Using a modified Boyden chamber method, SP was shown to act as a chemoattractant to pterygium fibroblasts and vascular endothelial cells, and this activity was diminish by blockade of its receptor (NK1). 3H-thymidine incorporation assays confirmed that our cell migration results were unrelated to SP-stimulated proliferation. A bead-based multiplex cytokine array detected secretion of pro-inflammatory cytokines (IL-6, IL-8 and CCL2) from SP stimulated pterygium and limbal epithelial cells. Using real-time RT-PCR and immunoblotting, we show that UVB stimulated transcription of the TAC1 gene followed by secretion of SP in ocular surface epithelial cell cultures. Finally, SP and NK1receptor immunoreactivity was identified in pterygium tissue, where overall, NK1receptors were up-regulated in pterygia. Furthermore, we identified a population of NK1 receptor positive mononuclear cells in pterygia that did not express lineage markers for T or B-Iymphocytes, macrophages or mast cells, but may represent immature haemopoietic cells that may have migrated in from the blood since these cells were also present in autologous conjunctival tissue. In summary, SP may contribute to the shape of pterygia by facilitating migration of fibroblasts and vascular endothelial cells into the normally avascular cornea. Additionally, UVB stimulates SP production in epithelial cells and the presence of SP contributes to inflammation in pterygia by inducing pro-inflammatory cytokine release. Finally, we identified a population of relatively immature, NK1 receptor positive cells in pterygia that may have been attracted by the presence of SP. Collectively, these results imply that SP may contribute to the pathogenesis of pterygia.
| Identifer | oai:union.ndltd.org:ADTP/258475 |
| Date | January 2007 |
| Creators | Chui, Jeanie Jin Yee, Medical Sciences, Faculty of Medicine, UNSW |
| Publisher | Publisher:University of New South Wales. Medical Sciences |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://unsworks.unsw.edu.au/copyright, http://unsworks.unsw.edu.au/copyright |
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