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Pigment Epithelium-Derived Factor (PEDF) in the Retina

Protective Effect against Photoreceptor Cell Degeneration
  • S. Patricia Becerra
  • Elena Alberdi
  • Alfredo Martinez
  • Luis M. Montuenga
  • Michel Cayouette
  • Claude Gravel

Abstract

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.

Keywords

Retinal Pigment Epithelial Retinitis Pigmentosa Cerebellar Granule Cell Retinoblastoma Cell Neurotrophic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    J. Tombran-Tink, G.J. Chader, and L.V. Johnson, 1991, PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity, Exp. Eye Res. 53:411–414.PubMedCrossRefGoogle Scholar
  2. 2.
    F.R. Steele, G.J. Chader, L.V. Johnson, and J. Tombran-Tink, 1993, Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family, Proc. Natl. Acad. Sci. USA 90:1526–1530.PubMedCrossRefGoogle Scholar
  3. 3.
    S.P. Becerra, 1997, Structure-function relationships of PEDF: A noninhibitory serpin with neurotrophic activity, Adv. Exp. Med. Biol. 425:223–237.PubMedGoogle Scholar
  4. 4.
    T. Taniwaki, S.P. Becerra, G.J. Chader, and J.P. Schwartz, 1995, Pigment epithelium-derived factor is a survival factor for cerebellar granule cells in culture, J. Neurochem. 64:2509–2517.PubMedCrossRefGoogle Scholar
  5. 5.
    T. Taniwaki, N. Hirashima, S.P. Becerra, G.J. Chader, R. Etcheberrigaray, and J.P. Schwartz, 1997, Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induce neurotoxicity, J. Neurochem. 68:26–32.PubMedCrossRefGoogle Scholar
  6. 6.
    T. Araki, T. Taniwaki, S.P. Becerra, G.J. Chader, and J.P. Schwartz, 1998, Pigment epithelium-derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death, J. Neurosci. Res. 53:7–15.PubMedCrossRefGoogle Scholar
  7. 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
  8. 8.
    R.J. Pignolo, V.J. Cristofalo, and M.O. Rotenberg, 1993, Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into G0 state, J. Biol. Chem. 268:8949–8957.PubMedGoogle Scholar
  9. 9.
    R. Huber and R.W. Carrell, 1989, Implications of the three-dimensional structure of ovantitrypsin for structure and function of serpin, Biochemistry 28:8951–8966.PubMedCrossRefGoogle Scholar
  10. 10.
    J. Guenther, H. Nick, and D. Monard, 1985, A glia-derived neurite-promoting factor with protease inhibitory activity, EMBO Journal 4:1963–1966.PubMedGoogle Scholar
  11. 11.
    S. Gloor, K. Odink, J. Guenther, H. Nick, and D. Monard, 1986, A glia-derived neurite promoting factor with protease inhibitory activity belongs to the protease nexins, Cell 47:687–693.PubMedCrossRefGoogle Scholar
  12. 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
  13. 13.
    E. Stratikos, E. Alberdi, P.G.W. Gettins, and S.P. Becerra, 1996, Characterization of human PEDF. overexpression in eukaryotic cells, Protein Science 5:2575–2582.PubMedCrossRefGoogle Scholar
  14. 14.
    J. Ortego, J. Escribano, S.P. Becerra, and M. Coca-Prados, 1996, Gene expression of the neurotrophic factor PEDF in the human ciliary epithelium: Synthesis and secretion into the aqueous humor, Invest. Ophthalmol. Vis. Sci. 37:2759–2767.PubMedGoogle Scholar
  15. 15.
    L.A. Perez-Mediavilla, C. Chew, P.A. Campochiaro, R.W. Nickells, V. Notario, D.J. Zack, and S.P. Becerra, 1998, Sequence and expression analysis of bovine pigment epithelium-derived factor (PEDF), Biochim. Biophys. Acta 1398:203–214.PubMedGoogle Scholar
  16. 16.
    V.K. Singh, G.J. Chader, and I.R. Rodriguez, 1998, Structural and comparative analysis of the mouse gene for pigment epithelium-derived factor (PEDF), Mol. Vis. 4:7–00.PubMedGoogle Scholar
  17. 17.
    J. Tombran-Tink, S.M. Shivaram, G.J. Chader, L.V. Johnson, and D. Bok, 1995, Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity, J. Neurosci. 15:4992–5003.PubMedGoogle Scholar
  18. 18.
    Y.-Q. Wu, V. Notario, G.J. Chader, and S.P. Becerra, 1995, Identification of pigment epithelium-derived factor in the interphotoreceptor matrix of bovine eyes, Protein Express. Purif. 6:447–456.CrossRefGoogle Scholar
  19. 19.
    Y.-Q. Wu and S.P. Becerra, 1996, Proteolytic activity directed towards pigment epithelium-derived factor in vitreous of bovine eyes: Implications of proteolytic processing, Invest. Ophthalmol. Vis. Sci. 37:1984–1993.PubMedGoogle Scholar
  20. 20.
    J.E. Morris, M. Yanagishita, and V.C. Hascall, 1987, Proteoglycans synthesized by embryonic chicken retina in culture: composition and compartmentauzation, Arch. Biochem. Biophys. 258:206–218.PubMedCrossRefGoogle Scholar
  21. 21.
    M. Kaneko, 1987, Interphotoreceptor matrix glycosaminoglycans in bovine eye, Ophthalmic Res. 19:330–337.PubMedCrossRefGoogle Scholar
  22. 22.
    G.S. Hageman and L.V. Johnson, 1987, Chondroitin 6-sulfate glycosaminoglycan is a major constituent of primate cone photoreceptor matrix sheaths, Curr. Eye Res. 6:639–646.PubMedGoogle Scholar
  23. 23.
    F. Murillo-Lopez, L. Politi, R. Adler, and A.T. Hewitt, 1991, Proteoglycan synthesis in cultures of murine retinal neurons and photoreceptors, Cell Mol. Neurobiol. 11:579–591.PubMedCrossRefGoogle Scholar
  24. 24.
    Y. Chu, L.N. Walker, S.L. Vijayasekaran, R.L. Cooper, K.V. Porrello, and I.J. Constable, 1992, Developmental study of chondroitin-6-sulphate in normal and dystrophic rat retina, Graefes Arch. Clin. Exp. Ophthalmol. 230:476–482.PubMedCrossRefGoogle Scholar
  25. 25.
    R.A. Landers and J.G. Hollyfield, 1992, Proteoglycans in the mouse interphotoreceptor matrix. VI. Evidence for photoreceptor synthesis of chondroitin sulfate proteoglycan using genetically fractionated retinas, Exp. Eye Res. 55:345–356.PubMedCrossRefGoogle Scholar
  26. 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. 27.
    E. Alberdi and S.P. Becerra, 1997, PEDF-binding activity to retinolastoma cells, Adv. Exp. Med. Biol. 425:307.Google Scholar

Copyright information

© Kluwer Academic / Plenum Publishers 1999

Authors and Affiliations

  • S. Patricia Becerra
    • 1
  • Elena Alberdi
    • 1
  • Alfredo Martinez
    • 2
  • Luis M. Montuenga
    • 1
    • 2
  • Michel Cayouette
    • 3
  • Claude Gravel
    • 3
  1. 1.Department of Histology and PathologySchool of Medicine University of NavarraPamplonaSpain
  2. 2.National Cancer InstituteCCBD, DCSBethesda
  3. 3.Laboratoire de Transfert de GènesCentre de Recherche Université Laval Robert-GiffardBeauportCanada

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