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S. Hoffmann, S. He, Y.H. Kim, C. Spee, G.K. Lang, G.E. Lang, S.J. Ryan, D.R. Hinton; Functional Involvement of the RAGE Receptor System in PVR Propagation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1434.
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To investigate the involvement of the pro–inflammatory RAGE receptor system and its ligands in proliferative vitreoretinopathy (PVR).
Surgically removed PVR membranes were immunohistochemically stained for the expression of the RAGE receptor system and its ligands S100B, HMGB–1, S100A12, S100A7 and S100A8. Furthermore, functional aspects of S100B and HMGB–1 on the proliferation, migration and smooth muscle actin positivity of retinal pigmented epithelial cells (RPE) were evaluated.
The RAGE receptor and its ligands S100B and S100A12 were strongly expressed in the excised PVR membranes. For HMGB–1 and S100A8, a weaker expression was seen, while S100A7 was not detected. RAGE was colocalized stromgly with RPE cells by double labeling for cytokeratin. Both HMGB–1 and S100B increased the proliferation and migration of RPE cells (p<0.05) in vitro. Furthermore, HMGB–1 induced a strong smooth muscle actin positivity of RPE cells after an exposure time of 5 days.
The RAGE multiligand system with its ligands S100A12, S100B, S100A8 and HMGB–1 may be involved in the propagation of PVR and should be further evaluated for feasibility as a therapeutic target.
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