[PEDF: an endogenous factor displaying potent neuroprotective, neurotrophic, and antiangiogenic activity]

Abstract

PEDF (pigment epithelium-derived factor) was first purified in 1989 from the conditioned medium of human retinal pigment epithelial cells as a factor with potent differentiating activity in human retinoblastoma cells. This discovery triggered intensive research directed at elucidating the biological activity of this new factor. The presence of PEDF was confirmed in several structures of the eye and other organs (i.e. liver, lung, kidney) in both prenatal and postnatal life, and in almost all parts of the central nervous system. The synthesis and secretion of PEDF is more effective in young cells and decreases during their aging. Although many findings suggest a receptoric nature of PEDF action, the receptor responsible for its neuroprotective, neurotrophic, and antiangiogenic effect still remains to be identified. PEDF is capable of regulating many physiological processes; for example, it stimulates the differentiation of human retinoblastoma cells to neurons and increases the growth and survival of photoreceptor cells of the retina and neurons of the central and peripheral nervous system. Furthermore, this factor also protects immature neuron cells from apoptosis. PEDF, probably the most potent endogenous inhibitor of angiogenesis, behaves as a functional antagonist of vascular endothelial growth factor (VEGF) and inhibits neovascularization. Endowed with neuroprotective, neurotrophic, and antiangiogenic potential, PEDF itself, or its biologically active fragment, is currently considered an agent of great interest in the future therapy of an array of neurological, ophthalmological, and oncological disorders.