Retinal glial (Müller) cells may play a major role in vascular eye diseases as they secrete vascular endothelial growth factor (VEGF), a hypoxia-induced angiogenic cytokine. They also release significant amounts of the anti-angiogenic factors, transforming growth factor (TGF)-β2, pigment epithelium derived factor (PEDF), and thrombospondin-1 (TSP-1). Exposure of human (MIO-M1) and guinea-pig Müller cells to hypoxia resulted in a decreased release of TGF-β2 and PEDF but in an elevated secretion of TSP-1. When retinal endothelial cells were exposed to VEGF/anti-angiogenic factor ratios mimicking those found in culture media of Müller cells under normoxia or hypoxia, their proliferation was significantly inhibited by TGF-β2, PEDF or TSP-1. Thus Müller cells may provide a permanent anti-proliferative condition for retinal endothelial cells.