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Y. Ogawa, S. Shimmura, T. Kawakita, N. Kato, H. Miyashita, S. Yoshida, K. Tsubota; Collagen Secretion From HSP 47-Expressing Conjunctival Basal Epithelia in Dry Eye Associated With Chronic Graft versus Host Disease. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5304.
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Conjunctival fibrosis such as symblephalon and fornix shortening is a prominent feature of conjunctival chronic graft versus host disease (cGVHD). The purpose of this study is to elucidate whether the conjunctival basal epithelia and mesenchymal interaction contibute to conjunctival fibrosis in the pathogenesis of cGVHD.
Conjunctival specimens from ten patients who had presented with dry eye as part of their symptoms of cGVHD were examined and compared with 5 normal subjects. Antibodies to CD4, CD8, CD34, HLA-DR, heat shock protein 47 (HSP47), and Ki67 were used for immunohistochemical analysis of conjunctival biopsies. The regions of interest in conjunctival epithelia and stroma were further assessed by transmission electron microscopy.
CD8+ T cells and macrophages accumulated around conjunctival basal epithelia through the disrupted basal lamina. The elevated expression of HSP47 on subepithelial fibroblasts in cGVHD patients was mostly detected in Ki67+ cells. Moreover, HSP47, a marker of collagen synthesis, was detected mainly in the conjunctival basal epithelia, but not in the superficial epithelia. Under electron microscopic observation, collagen bundles were secreted from conjunctival basal epithelia, in which collagen bundle possesses abnormal diameter and periodicity. However, these observations were infrequently observed in the conjunctiva from normal subjects.
CD8+ T cells accumulating in the basal epithelia play a critical role in the destructive potential during GVHD pathogenesis. Conjunctival basal epithelial cells are transformed to a HSP47-expressing mesenchymal phenotype facilitating the production of collagen bundles.
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