Involvement of the RAGE Receptor System and its ligands in the propagation of prolifervative vitreoretinopathy (PVR)

S.Hoffmann
Universitaetsaugenklinik Ulm, Ulm, Germany

Purpose: To investigate the involvement of the pro-inflammatory RAGE receptor system and its ligands in proliferative vitreoretinopathy (PVR).
Methods: 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.
Results: 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.
Conclusions: 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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