gms | German Medical Science

Pigment epithelium-derived factor (PEDF) is a 50 KDa neurotrophic and antiangiogenic factor, first identified in conditioned medium of cultured human foetal pigment epithelial cells inducing neuronal differentiation on cultured human Y-79 retinoblastoma cells. PEDF has been shown both in vivo and in vitro, to be one of the most potent antiangiogenic factors, and to have neuroprotective effects in various neuronal cell types, as well as survival properties on glial cells. With the exception of a PEDF immunohistochemical reaction of motor neurons of human and rat spinal cord, thus far, there are no studies about the PEDF localization in the CNS. To find out more about the role of PEDF in the CNS, we investigated the PEDF content and localization in pre- and postnatal development.

PEDF content was analysed in Western blots of whole rat brain homogenates from animals between embryonic day sixteen and three months of age. Double labelling immunohistochemistry to detect the presence of PEDF in neurons (Neu-N), glial cells (GFAP) or blood vessels (endothelial cell marker von-Willebrand-Factor), was performed in rat brains between birth and three months of age.

PEDF content of the entire brain is high during early embryogenesis and decreases by about 40% already at birth. With increasing postnatal age, PEDF content decreases even further, but not to the same degree as during early embryogenesis. Immunohistochemistry and cell specific double labelling indicate that there are mainly two cell types that are positive for PEDF in the brain: endothelial cells lining the vascular walls, and neurons. PEDF appeared to stain all endothelial cells and was especially strong at birth and early age and decreased in staining intensity with increasing age. PEDF labelling of neuronal cells increased in number and intensity with increasing maturity. Within the adult brain, neurons in many cortical areas were positive for PEDF, as well as cells of the dentate gyrus of the hippocampus and the cerebellar granular cells.

PEDF content during embryogenesis and the strong labelling of vessels at a young age indicate that PEDF may play an important role during brain neuronal and vascular development. Furthermore, the localization of PEDF in specific areas of the adult brain, open the possibility of finding other important effects of this factor on the central nervous system.