Angiogenesis-related factors derived from retinal glial (Muller) cells in hypoxia

Retinal glial (Muller) 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)-beta2, pigment epithelium derived factor (PEDF), and thrombospondin-1 (TSP-1). Exposure of human (MIO-M1) and guinea-pig Muller cells to hypoxia resulted in a decreased release of TGF-beta2 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 Muller cells under normoxia or hypoxia, their proliferation was significantly inhibited by TGF-beta2, PEDF or TSP-1. Thus Muller cells may provide a permanent anti-proliferative condition for retinal endothelial cells.