Thrombospondin-1 Is Produced by Retinal Glial Cells and Inhibits the Growth of Vascular Endothelial Cells

• Published in: Ophthalmic research Vol. 52; no. 2; pp. 81 - 88
• Main Authors: Yafai, Yousef, Eichler, Wolfram, Iandiev, Ianors, Unterlauft, Jan-Darius, Jochmann, Claudia, Wiedemann, Peter, Bringmann, Andreas
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2014
• Subjects: Animals; Blotting, Western; Cattle; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - pathology; Enzyme-Linked Immunosorbent Assay; Ependymoglial Cells - metabolism; Humans; Immunohistochemistry; Microscopy, Confocal; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Original Paper; Phosphorylation; Rats; Rats, Long-Evans; Reperfusion Injury - metabolism; Retinal Diseases - metabolism; Thrombospondin 1 - metabolism; Thrombospondin 1 - pharmacology; Vascular Endothelial Growth Factor A - pharmacology; Vimentin - metabolism; Angiogenesis; Diabetic retinopathy; Ischemia; Vascular endothelium; Retina; Glia; Thrombospondin
• ISSN: 0030-3747; 1423-0259; 1423-0259
• DOI: 10.1159/000362371

Background/Aims: By the release of antiangiogenic factors, Müller glial cells provide an angiostatic environment in the normal and ischemic retina. We determined whether Müller cells produce thrombospondin-1 (TSP-1), a known inhibitor of angiogenesis. Methods: Secretion of TSP-1 by cultured Müller cells was determined with ELISA. Slices of rat retinas and surgically excised retinal membranes of human subjects were immunostained against TSP-1 and the glial marker vimentin. The effects of TSP-1 on the growth of bovine retinal endothelial cells (BRECs) and activation of ERK1/2 were determined with DNA synthesis and migration assays, and Western blotting, respectively. Results: Cultured Müller cells secrete TSP-1 under normoxic and hypoxic (0.2% O 2 ) conditions. Secretion of TSP-1 was increased in hypoxia compared to normoxia. In rat retinal slices, glial, retinal ganglion, and possibly horizontal cells were stained for TSP-1. Retinal glial cells in preretinal membranes from human subjects with nonhypoxic epiretinal gliosis (macular pucker) and proliferative diabetic retinopathy, respectively, were immunopositive for TSP-1. Exogenous TSP-1 reduced the VEGF-induced proliferation and migration of BRECs and decreased the phosphorylation level of ERK1/2 in BRECs. Conclusion: The data suggest that Müller cells are one major source of TSP-1 in the normal and ischemic retina. Glia-derived TSP1 may inhibit angiogenic responses in the ischemic retina.