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N. Di Girolamo, M.T. Coroneo, D. Wakefield; The UVB-Elicited Induction of MMP-1 in Pterygium Epithelial Cells Is Mediated Through a MAPK-Dependent Pathway . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1322.
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Purpose:Ptergyia are common lesions of the ocular surface characterized by tissue remodeling, proliferation, angiogenesis and inflammation. Extensive epidemiological evidence implicates ultraviolet (UV) light in the pathogenesis of this disease. In this study we investigated the effect of UV radiation on the expression of MMP-1 in pterygia and relevant ocular surface epithelial cells. Methods:Immunohistochemistry was performed on pterygium, conjunctival, limbal and corneal tissue specimens for MMP-1 and p63 expression. Primary cultures of pterygium, conjunctival, and limbal epithelial cells were established, expanded, and exposed to varying amounts of UVB. Cell and tissue-derived supernatants and total RNA was harvested and analyzed by Western blotting, gelatin zymography and RT-PCR for MMP and TIMP expression. Results:Enhanced expression of MMP-1 protein was observed in pterygium as compared to conjunctival, limbal, and corneal specimens. Interestingly, p63 immunoreactivity co-localized with MMP-1 positive epithelium. A dose and time-dependent increase in MMP-1 protein and mRNA was noted when pterygium and limbal but not conjunctival epithelial cells were exposed to UVB. Furthermore, MMP-2, MMP-9 and the TIMPs were not modulated by this treatment. MMP-1 was also enhanced in UVB-irradiated pterygium specimens. The induction of MMP-1 was not mediated by a soluble factor but was significantly inhibited with PD98059, a specific inhibitor of the ERK1/2 MAPK pathway. While SB203580, an inhibitor of JNK and p38 MAPK pathways had no effect on MMP-1 following UVB-irradiation. Conclusions:Collectively, these data support the hypothesis of the likely involvement of UV light and MMPs in the development of pterygia and imply that ocular protection from UV light may be one form of disease prevention.
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