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T.M. Nolan, N. Di Girolamo, M.T. Coroneo, D. Wakefield; The Effects of Ultraviolet Irradiation on Growth Factor Expression in Pterygium . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1320.
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Purpose: Ultraviolet (UV) light is one of the major factors implicated in the pathogenesis of pterygium. The mechanism by which UV light induces this disease remains elusive. The aim of this study was to evaluate the effects of UVB irradiation on the expression of growth factors in cultured pterygium epithelial cells, to demonstrate their distribution within pterygium and to determine the effects of these growth factors on pterygium formation Methods: We cultured pterygial epithelial cells from pterygium explants and these cells were exposed to 20mJ/cm2 of UVB. Total RNA was extracted and analyzed using microarray technology to determine the differential expression of growth factor and cytokine related genes. Semi-quantitative RT-PCR was used to corroborate this data. Conditioned media derived from cells exposed to UVB irradiation was analysed for protein expression by enzyme linked immuno-absorbant assay (ELISA). Immunohistochemistry was used to evaluate the distribution in pterygium tissue. The effects of these growth factors on pterygial tissue was then analysed. Results: Analysis of the hybridization signals revealed that the genes encoding Heparin-Binding Epidermal growth factor-like Growth Factor (HB-EGF), Fibroblast Growth Factor 3 (FGF3) and Cytotoxic Trail Ligand Receptor (TRAIL) were consistently elevated at 6 and 12 hours after UVB treatment. These were augmented in culture supernatants following the same treatment. Furthermore, HB-EGF reactivity was identified in the epithelium and vasculature of pterygium by immunohistochemistry. HB-EGF was present in normal limbal epithelium, although it was not induced in cultured limbal epithelial cells by UV irradiation. These growth factors exerted growth promoting forces on pterygium derived tissue. Conclusion: HB-EGF is a potent mitogen, localised in pterygium tissue and significantly induced by UVB in pterygium derived epithelial cells. We postulate that this growth factor is a major driving force in the development of pterygia and a means by which UV irradiation causes the pathogenesis of pterygium.
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