title: Thrombospondin-1 is produced by retinal glial cells and inhibits the growth of vascular endothelial cells.
abstract: OBJECTIVE
  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% O2) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Yafai
authors.forename: Wolfram
authors.initials: W
authors.lastname: Eichler
authors.forename: Ianors
authors.initials: I
authors.lastname: Iandiev
authors.forename: Jan-Darius
authors.initials: JD
authors.lastname: Unterlauft
authors.forename: Claudia
authors.initials: C
authors.lastname: Jochmann
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D063928:Ependymoglial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000378:metabolism; D012164:Retinal Diseases / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3