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D. Papalkar, N. Di Girolamo, D. Wakefield, C.L. Geczy; Inflammation–Associated S100 Proteins in Pterygia and Tears . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4983.
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S100 proteins are a vertebrate–restricted family of calcium–binding proteins that regulate various important intra– and extracellular functions such as regulation of cell proliferation and differentiation. Three inflammation–associated members, S100A8, A9 and A12, are constitutively expressed in neutrophils and monocytes and induced in some other cells during inflammation, UVA irradiation and oxidative stress. The A8/A9 complex has anti–microbial activity, and can inhibit matrix metalloproteinase activity. A8 is an oxidant scavenger and A12 is pro–inflammatory. Because of the role of UV exposure in the pathogenesis of pterygia, expression of these proteins in pterygia and tears was examined.
Immunohistochemistry was performed on formalin–fixed, paraffin–embedded surgically excised pterygia and conjunctival specimens, and one pterygium attached to the globe. Western blotting and ELISA was performed on protein freshly extracted from excised pterygia and conjunctival specimens. A8 and A9 content in tears was determined by Western blotting.
A8 and A9 were strongly co–expressed in contiguous areas of superficial epithelium of all pterygium specimens, but expression in the basal epithelial layer was weak or negative. They were predominantly located intracytoplasmically, but were also present in the nucleus in some cells. A8 and A9 were localised to the epithelium surrounding the advancing pterygium head. A12 was weakly expressed in pterygium epithelium in only a few specimens and was mainly confined to neutrophils within vessels. A8 and A9 monomers were confirmed by Western blotting. A8 and A9 levels in pterygia were 0.79 and 0.21 ng / µg total protein, respectively. A8 and A9, but not A12 were also present in tears from normal controls and patients with pterygium in approximately equal amounts.
A8 and A9 expression in the superficial epithelium of pterygia, particularly at the advancing pterygium head, suggests that these proteins are involved in its pathogenesis. They may protect against UV–mediated oxidative damage or be involved in differentiation of the pterygium epithelium. A12 could contribute to the inflammatory component of this disease. As components of normal tears, A8 and A9 may participate in microbial defence, particularly to yeast pathogens, and regulate MMP activity on the ocular surface.
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