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U.C. Welge-Lussen, A. Neubauer, S.G. Priglinger, A. Fuchs, A. May, K. Eibl, C. Alge, A.S. Neubauer, A. Kampik; Tissue Transglutaminase Cross-Linking of Laminin and Fibronectin in Proliferative Vitreoretinopathy (PVR) Membranes and Cultured Human Retinal Pigment Epithelium (RPE) Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2962.
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Purpose: : In proliferative vitreoretinopathy (PVR) epi- and subretinal fibrocellular membranes containing modified retinal pigment epithelial (RPE) cells among others develop. In a previous study we have shown that RPE cells synthesize increased amounts of tissue transglutaminase (tTG) following treatment with transforming growth factor beta2 (TGF-ß2). tTG is an enzyme catalyzing irreversible crosslinking of extracellular matrix (ECM) components like fibronectin and laminin, both major components of PVR membranes. This study investigates the role of tTG, laminin and fibronectin for the accumulation of ECM by transglutaminases in these membranes. Methods: In vitro, RPE cells were treated with TGF-ß2, basic fibroblast growth factor, interleukin-6, and interleukin-1beta. Their effect on laminin and fibronectin expression was studied on Northern- and Western-blot analysis. Furthermore, a Western-blots for e-(g-glutamyl)-lysine were performed. In PVR-membranes localization of laminin, tTG, and the reaction product e-(g-glutamyl)-lysine was investigated immunohistochemically. Co-localization was studied with a fluorescence laser scanning microscope. Results: In RPE cells, laminin and fibronectin mRNA and protein formation could be stimulated by TGF-ß2 treatment. Additionally the reaction product of tTgase e-(g-glutamyl)-lysine was significantly increased by TGF-ß2. The other cytokines showed only little effect. In PVR-membranes, staining for laminin and fibronectin was co-localized with tTG and e-(g-glutamyl)-lysine. Conclusions: These findings underline the importance of tTG for ECM crosslinking in PVR-membranes. In vitro, the process can be stimulated by TGF-ß2, a growth factor known to be increased in the vitreous of PVR. Inhibition of tTG may offer a novel approach to preventing PVR development.
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