Skip to main content

Pigment Epithelium-Derived Factor (PEDF) in the Retina

Protective Effect against Photoreceptor Cell Degeneration

  • Chapter
Book cover Retinal Degenerative Diseases and Experimental Therapy

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  3. S.P. Becerra, 1997, Structure-function relationships of PEDF: A noninhibitory serpin with neurotrophic activity, Adv. Exp. Med. Biol. 425:223–237.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  10. J. Guenther, H. Nick, and D. Monard, 1985, A glia-derived neurite-promoting factor with protease inhibitory activity, EMBO Journal 4:1963–1966.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  21. M. Kaneko, 1987, Interphotoreceptor matrix glycosaminoglycans in bovine eye, Ophthalmic Res. 19:330–337.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  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.

    CAS  Google Scholar 

  27. E. Alberdi and S.P. Becerra, 1997, PEDF-binding activity to retinolastoma cells, Adv. Exp. Med. Biol. 425:307.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Patricia Becerra .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Kluwer Academic / Plenum Publishers

About this chapter

Cite this chapter

Becerra, S.P., Alberdi, E., Martinez, A., Montuenga, L.M., Cayouette, M., Gravel, C. (1999). Pigment Epithelium-Derived Factor (PEDF) in the Retina. In: Hollyfield, J.G., Anderson, R.E., LaVail, M.M. (eds) Retinal Degenerative Diseases and Experimental Therapy. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-33172-0_49

Download citation

  • DOI: https://doi.org/10.1007/978-0-585-33172-0_49

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46193-4

  • Online ISBN: 978-0-585-33172-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics