PIGMENT EPITHELIUM-DERIVED FACTOR IS A SURVIVAL FACTOR FOR CEREBELLARGRANULE CELLS IN CULTURE

Pigment epithelium-derived factor (PEDF), purified from human fetal re tinal pigment epithelium cell culture medium, was shown to potentiate the differentiation of human Y-79 retinoblastoma cells. To investigate potential neurotrophic effects of PEDF on neurons other than those of retinal derivation, we used cultures of cerebellar granule cells. The number of cerebellar granule cells was significantly larger in the pr esence of PEDF, as demonstrated by an assay for viable cells that uses 3-(4, xymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt, conversion, by cell count, and by immunocytochemistry. The effect of P EDF showed a dose-response relationship, with a larger effect in chemi cally defined medium than in serum-containing medium [ED(50) = 30 ng/m l (0.70 nM) in chemically defined medium and 100 ng/ml (2.3 nM) in ser um-containing medium]. PEDF had no effect on incorporation of bromodeo xyuridine (cell proliferation) or on neurofilament content (neurite ou tgrowth) measured by an enzyme-linked immunoadsorbent assay. These res ults demonstrate that PEDF has a neurotrophic survival effect on cereb ellar granule cells in culture and suggest the possibility that it may affect other CNS neurons as well.