The role of matricellular proteins thrombospondin-1 and osteonectin during RPE cell migration in proliferative vitreoretinopathy

Abstract

Purpose: To investigate the hypothesis that the Matricellular proteins thrombospondin 1 (TSP1), tenascin (TN) and Secreted Protein Acidic and Rich in Cysteine (SPARC) modulate the migration of RPE cells in the epiretinal membranes of proliferative vitreoretinopathy. Methods: Ten PVR epiretinal membranes were studied by immunohistochemical methods in which aggregates of RPE cells were identified by their expression of a broad range of cytokeratins. RPE subsets containing migratory RPE cells were detected by immunoreactivity for the monoclonal antibody RGE53 (which detects an epitope on cytokeratin-18 on motile RPE cells). Co-localisation of the RPE subsets with the glycoproteins TSP-1, SPARC and TN was evaluated. Results: Nineteen migratory RPE (RGE53 positive) subsets and 13 RPE (RGE53 negative) subsets were identified. All of the RGE53+ subsets colocalised with TSP1 and SPARC and 17 with TN. Ten of the RGE53- aggregates stained for TN, 6 for SPARC and 5 for TSP1. The association between the presence of RGE53+ cells in the RPE cell aggregates and TSP1 immunoreactivity in the aggregates was significant (p < 0.001), and there was a comparable significant association between RGE53+ cells and SPARC (p < 0.001). No such association was detected for RGE53+ cells and TN (p > 0.2). Conclusions: The findings support the concept that the migration of retinal pigment cells in epiretinal membranes is modulated by TSP1 and SPARC and thus that these two proteins ultimately may represent therapeutic targets in the management of the membranes.