Pigment Epithelium-Derived Factor (PEDF) in the Retina
Pigment epithelium-derived factor (PEDF) was first described as a secreted product of human fetal retinal pigment epithelial (RPE) cells in culture with a potent neuronal differentiating activity on human retinoblastoma Y-79 cells.1 It was reported that PEDF at nanomolar concentrations induces a morphological differentiation of Y-79 cells, characterized by the elongation of neurite-like processes and the expression of neuronal markers, e.g., neuron-specific enolase and the 200-kDa neurofilament subunit.2 It was shown later that PEDF can also induce the differentiation of cells from another human retinoblastoma, the Weri cells.3 While its role in vivo on retina cells is not known yet, its origin and these activities suggest that PEDF may play a role as a neurotrophic factor for the retina. In this regard, evidence of its effects on neurons from the CNS and PNS is accumulating rapidly and supports the notion that PEDF is a multipotent neurotrophic factor that acts upon various types of neurons and from different species. For example, it promotes the survival of rat cerebellar granule cell (CGC) neurons in culture,4 including protection against glutamate neurotoxicity5 and against both natural and induced apoptosis in vitro;6 it promotes survival and differentiation of developing avian and murine spinal motor neurons.7 Given the important biological activities of PEDF, it is of interest to investigate its mechanism of action on the retina. Therefore, the overall objective of this review will be to discuss the biochemistry of PEDF in the context of a potential use as a relevant neurotrophic factor for the retina.
KeywordsRetinal Pigment Epithelial Retinitis Pigmentosa Cerebellar Granule Cell Retinoblastoma Cell Neurotrophic Activity
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- 7.L.J. Houenou, A.P. D’Costa, L. Li, V.L. Turgeon, C. Enyadike, E. Alberdi, and S.P. Becerra, Pigment epithelium-derived factor (PEDF) promotes the survival and differentiation of developing spinal motor neurons (in preparation).Google Scholar
- 12.S.P. Becerra, A. Sagasti, P. Spinella, and V. Notario, 1995, Pigment epithelium-derived factor (PEDF) behaves like a non-inhibitory serpin: neurotrophic activity does not require the serpin reactive loop, J. Biol. Chem. 270:25,992–25,999.Google Scholar
- 26.E. Alberdi, C.C. Hyde, and S.P. Becerra, 1998, Pigment epithelium-derived factor (PEDF) binds to glycosaminoglycans: Analysis of binding site, Biochemistry 37:10,643–10,652.Google Scholar
- 27.E. Alberdi and S.P. Becerra, 1997, PEDF-binding activity to retinolastoma cells, Adv. Exp. Med. Biol. 425:307.Google Scholar