Skip to main content
SpringerLink
Log in

Control of Neovascularization and Cell Survival in the Eye by PEDF

  • Chapter
Ocular Angiogenesis

Part of the book series: Opthalmology Research ((OPHRES))

  • 874 Accesses

Abstract

Pathological angiogenesis is by far the most common aspect of eye diseases. Corneal lesions and inflammatory ocular diseases have a strong angiogenesis component and are the most common causes of visits to ophthalmologists. Proliferative diabetic retinopathy (PDR) and age-related macular degeneration (AMD) affect more than 7 million people in the United States alone. As described elsewhere in this volume, pathological angiogenesis is also an important component of many other diseases of the eye. Controlling blood vessel growth, therefore, offers a unique opportunity to affect a wide spectrum of physiological and pathological functions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover 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. Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell 1996;87:1153–1155.

    Article  PubMed  CAS  Google Scholar 

  2. Bikfalvi A, Bicknell R. Recent advances in angiogenesis, anti-angiogenesis and vascular targeting. Trends Pharmacol Sci 2002;23:576–582.

    Article  PubMed  CAS  Google Scholar 

  3. Folkman J. Role of angiogenesis in tumor growth and metastasis. Sem Oncol 2002;29:15–18.

    CAS  Google Scholar 

  4. Tombran-Tink J, Barnstable CJ. Therapeutic prospects for PEDF: more than a promising angiogenesis inhibitor. Trends Mol Med 2003;9:244–250.

    Article  PubMed  CAS  Google Scholar 

  5. Stalmans I, Ng YS, Rohan R, et al. Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest 2002;109:327–336.

    Article  PubMed  CAS  Google Scholar 

  6. Ishida S, Usui T, Yamashiro K, et al. VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J Exp Med 2003;198:483–89.

    Article  PubMed  CAS  Google Scholar 

  7. Tombran-Tink J, Johnson LV. Neuronal differentiation of retinoblastoma cells induced by edium conditioned by human RPE cells. Invest Opthalmol Vis Sci 1989;30:1700–1707.

    CAS  Google Scholar 

  8. Tombran-Tink J, Chader GG, Johnson LV. PEDF: a pigment epithelium derived factor with potent neuronal differentiative activity. Exp Eye Res 1991;53:411–414.

    Article  PubMed  CAS  Google Scholar 

  9. Tombran-Tink J, Bamstable CJ. PEDF: A multifaceted neurotrophic factor. Nat Rev Neurosci 2003;4:628–636.

    Article  PubMed  CAS  Google Scholar 

  10. Tombran-Tink J, Lara N, Apricio SE, et al. Retinoic acid and dexamethasone regulate the expression of PEDF in proliferating cells. Exp Eye Res 2004;78:945–955.

    Article  PubMed  CAS  Google Scholar 

  11. Tombran-Tink J, Mazaruk K, Chung D, Linker T, Chader GJ, Rodriguez I. Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin. Mol Vis 1996;2:11.

    PubMed  CAS  Google Scholar 

  12. Tombran-Tink J, Barnstable CJ. Osteoblasts and osteoclasts express PEDF, VEGF-A isoforms, and VEGF receptors: possible mediators of angiogenesis and matrix remodeling in the bone. Biochem Biophys Res Comm 2004;316:573–579.

    Article  PubMed  CAS  Google Scholar 

  13. Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 1999;285:245–248.

    Article  PubMed  CAS  Google Scholar 

  14. Tombran-Tink J, Shivaram SM, Chader GJ, Johnson LV, Bok D. Expression,, secretion and age-related down regulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. J Neurosci 1995;15:4992–5003.

    PubMed  CAS  Google Scholar 

  15. Karakousis PC, John SK, Behling KC, et al. Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues. Mol Vis 2001;7:154–163.

    PubMed  CAS  Google Scholar 

  16. Quan GM, Ojaimi J, Nadesapillai AP, Zhou H, Choong PF. Resistance of epiphyseal cartilage to invasion by osteosarcoma is likely to be due to expression of antiangiogenic factors. Pathobiology 2002;70:361–367.

    Article  PubMed  CAS  Google Scholar 

  17. Palmieri D, Watson JM, Rinehart CA. Age-related expression of PEDF/EPC-1 in human endometrial stromal fibroblasts: implications for interactive senescence. Exp Cell Res 1999;247:142–147.

    Article  PubMed  CAS  Google Scholar 

  18. Mori K, Duh E, Gehlbach P, et al. Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J Cell Physiol 2001;188:253–263.

    Article  PubMed  CAS  Google Scholar 

  19. Mori K, Gehlbach P, Ando A, McVey D, Wei L, Campochiaro PA. Regression of ocular eovascularization in response to increased expression of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 2002;43:2428–2434.

    PubMed  Google Scholar 

  20. Raisler BJ, Berns KI, Grant MB, Beliaev D, Hauswirth WW. Adeno-associated virus type-2 expression of pigmented epithelium-derived factor or Kringles 1–3 of angiostatin reduce retinal neovascularization. Proc Natl Acad Sci USA 2002;99:8909–8914.

    Article  PubMed  CAS  Google Scholar 

  21. Auricchio A, Behling KC, Maguire AM, et al. Inhibition of retinal neovascularization by intraocular viral-mediated delivery of anti-angiogenic agents. Mol Ther 2002;6:490–194.

    Article  PubMed  CAS  Google Scholar 

  22. Mori K, Gehlbach P, Yamamoto S, et al. AAV-mediated gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 2002;43:1994–2000.

    PubMed  Google Scholar 

  23. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HE. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219:983–985.

    Article  PubMed  CAS  Google Scholar 

  24. Liu H, Ren JG, Cooper WL, Hawkins CE, Cowan MR, Tong PY. Identification of the anti-vasopermeability effect of pigment epithelium-derived factor and its active site. Proc Natl Acad Sci USA 2004;101:6605–6610.

    Article  PubMed  CAS  Google Scholar 

  25. Ohno-Matsui K, Morita I, Tombran-Tink J, et al. Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF. J Cell Physiol 2001;189:323–333.

    Article  PubMed  CAS  Google Scholar 

  26. Sawant S, Aparicio S, Tink AR, Lara N, Barnstable CJ, Tombran-Tink J. Regulation of factors controlling angiogenesis in liver development: a role for PEDF in the formation and maintenance of normal vasculature. Biochem Biophys Res Commun 2004;325:408–413.

    Article  PubMed  CAS  Google Scholar 

  27. Ogata N, Tombran-Tink J, Nishikawa M, et al. Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy and high in rhegmatogenous retinal detachment. Am J Ophthalmol 2001;132:378–382.

    Article  PubMed  CAS  Google Scholar 

  28. Spranger J, Osterhoff M, Reimann M, et al. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes 2001;50:2641–2645.

    Article  PubMed  CAS  Google Scholar 

  29. Ogata N, Nishikawa M, Nishimura T, Mitsuma Y, Matsumura M. Inverse levels of pigment epithelium-derived factor and vascular endothelial growth factor in the vitreous of eyes with rhegmatogenous retinal detachment and proliferative vitreoretinopathy. Am J Ophthalmol 2002;133:851–852.

    Article  PubMed  CAS  Google Scholar 

  30. Holekamp NM, Bouck N, Volpert O. Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration. Am J Ophthalmol 2002;134:220–227.

    Article  PubMed  CAS  Google Scholar 

  31. Ogata N, Nishikawa M, Nishimura T, Mitsuma Y, Matsumura M. Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy. Am J Ophthalmol 2002;134:348–353.

    Article  PubMed  CAS  Google Scholar 

  32. Matsuoka M, Ogata N, Otsuji T, Nishimura T, Takahashi K, Matsumura M. Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovas-cular membranes and polypoidal choroidal vasculopathy. Br J Ophthalmol 2004;88:809–815.

    Article  PubMed  CAS  Google Scholar 

  33. Lara N, Aparicio S, Sawant S, et al. PEDF regulates expression of VEGF-R2 and VEGF-R3 in the retina: A possible mechanism for controlling angiogenesis in the eye. (Submitted).

    Google Scholar 

  34. Hutchings H, Maitre-Boube M, Tombran-Tink J, Plouet J. Pigment epithelium-derived factor exerts opposite effects on endothelial cells of different phenotypes. Biochem Biophys Res Commun 2002;294:764–769.

    Article  PubMed  CAS  Google Scholar 

  35. Volpert OV, Zaichuk T, Zhou W, et al. Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nat Med 2002;8:349–357.

    Article  PubMed  CAS  Google Scholar 

  36. Barreiro R, Schadlu R, Herndon J, et al. The role of Fas-FasL in the development and treatment of ischemic retinopathy. Invest Ophthalmol Vis Sci 2003;44:1282–1286.

    Article  PubMed  Google Scholar 

  37. Kataoka T, Budd RC, Holler N, et al. The caspase-8 inhibitor FLIP promotes activation of NF-KB and Erk signaling pathways. Curr Biol 2000;10:640–648.

    Article  PubMed  CAS  Google Scholar 

  38. Zaichuk TA, Shroff EH, Emmanuel R, Filleur S, Nelius T, Volpert OV. Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med 2004;199:1513–1522.

    Article  PubMed  CAS  Google Scholar 

  39. Lanza RP, Cibelli JB, Blackwell C, et al. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 2000;288:665–669.

    Article  PubMed  CAS  Google Scholar 

  40. Crawford SE, Stellmach V, Ranalli M, et al. Pigment epithelium-derived factor (PEDF) in neuroblastoma: a multifunctional mediator of Schwann cell antitumor activity. J Cell Sci 2001;l14:4421–1428.

    Google Scholar 

  41. Li S, Chen Y, Wei H. Muscle pigment epithelium-derived factor gene associating with tumorigenesis of B16 melanoma. Chinese J Pathol 2001;30:281–284.

    CAS  Google Scholar 

  42. Guan M, Yam HF, Su B, et al. Loss of pigment epithelium derived factor expression in glioma progression. J Clin Pathol 2003;56:277–282.

    Article  PubMed  CAS  Google Scholar 

  43. Mahtabifard A, Merritt RE, Yamada RE, Crystal RG, Korst RJ. In vivo gene transfer of pigment epithelium-derived factor inhibits tumor growth in syngeneic murine models of thoracic malignancies. J Thorac Cardiovasc Surg 2003;126:28–38.

    Article  PubMed  CAS  Google Scholar 

  44. Abe R, Shimizu T, Yamagishi S, et al. Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. Am J Pathol 2004;164:1225–1232.

    PubMed  CAS  Google Scholar 

  45. Garcia M, Fernandez-Garcia NI, Rivas V, et al. Inhibition of xenografted human melanoma growth and prevention of metastasis development by dual antiangiogenic/antitumor activities of pigment epithelium-derived factor. Cancer Res 2004;64:5632–5642.

    Article  PubMed  CAS  Google Scholar 

  46. Wang L, Schmitz V, Perez-Mediavilla A, Izal I, Prieto J, Qian C. Suppression of angiogenesis and tumor growth by adenoviral-mediated gene transfer of pigment epithelium-derived factor. Mol Ther 2003;8:72–79.

    Article  PubMed  CAS  Google Scholar 

  47. Matsumoto K, Ishikawa H, Nishimura D, Hamasaki K, Nakao K, Eguchi K. Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma. Hepatology 2004;40:252–259.

    Article  PubMed  CAS  Google Scholar 

  48. Uehara H, Miyamoto M, Kato K, et al. Expression of pigment epithelium-derived factor decreases liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma. Cancer Res 2004;64:3533–3537.

    Article  PubMed  CAS  Google Scholar 

  49. Doll JA, Stellmach VM, Bouck NP, et al. Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas. Nat Med 2003;9:774–780.

    Article  PubMed  CAS  Google Scholar 

  50. Cao W, Tombran-Tink J, Chen W, Mrazek D, Elias R, McGinnis JF. Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death. J Neurosci Res 1999;57:789–800.

    Article  PubMed  CAS  Google Scholar 

  51. Cao W, Tombran-Tink J, Elias R, Sezate S, Mrazek D, McGinnis JF. In vivo protection of photoreceptors from light damage by pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 2001;42:1646–1652.

    PubMed  CAS  Google Scholar 

  52. Jablonski MM, Tombran-Tink J, Mrazek DA, Iannaccone A. Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal. J Neurosci 2000;20:7149–7157.

    PubMed  CAS  Google Scholar 

  53. Ogata N, Wang L, Jo N, et al. Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury. Curr Eye Res 2001;22:245–252.

    Article  PubMed  CAS  Google Scholar 

  54. Taniwaki T, Hirashima N, Becerra SP, Chader GJ, Etcheberrigaray R, Schwartz JP. Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity. J Neurochem 1997;68:26–32.

    Article  PubMed  CAS  Google Scholar 

  55. DeCoster MA, Schabelman E, Tombran-Tink J, Bazan NG. Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons. J Neurosci Res 1999;56:604–610.

    Article  PubMed  CAS  Google Scholar 

  56. Bilak MM, Corse AM, Bilak SR, Lehar M, Tombran-Tink J, Kuncl RW. Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neu-rodegeneration. J Neuropathol Exp Neurol 1999;58:719–728.

    PubMed  CAS  Google Scholar 

  57. Alberdi E, Aymerich MS, Becerra SP. Binding of pigment epithelium-derived factor (PEDF) to retinoblastoma cells and cerebellar granule neurons. Evidence for a PEDF receptor. J Biol Chem 1999;274:31,605–31,612.

    Article  PubMed  CAS  Google Scholar 

  58. Yabe T, Wilson D, Schwartz JP. NFkappaB activation is required for the neuroprotective effects of pigment epithelium-derived factor (PEDF) on cerebellar granule neurons. J Biol Chem 2001;276:43,313–43,319.

    Article  PubMed  CAS  Google Scholar 

  59. Tombran-Tink J, Aparicio S, Xu X, et al. PEDF and the serpins: phylogeny, sequence conservation, and functional domains. J Structural Biol 2005;151:130–150.

    Article  CAS  Google Scholar 

  60. Simonovic M, Gettins PG, Volz K. Crystal structure of human PEDF, a potent anti-angiogenic and neurite growth-promoting factor. Proc Natl Acad Sci USA 2001;98:11,131–11,135.

    Article  PubMed  CAS  Google Scholar 

  61. Kozaki K, Miyaishi O, Koiwai O, et al. Isolation, purification, and characterization of a collagen-associated serpin, caspin, produced by murine colon adenocarcinoma cells. J Biol Chem 1998;273:15,125–15,130.

    Article  PubMed  CAS  Google Scholar 

  62. Meyer C, Notari L, Becerra SP. Mapping the type I collagen-binding site on pigment epithelium-derived factor. Implications for its antiangiogenic activity. J Biol Chem 2002;277:45,400–45,407.

    Article  PubMed  CAS  Google Scholar 

  63. Alberdi E, Hyde CC, Becerra SP. Pigment epithelium-derived factor (PEDF) binds to gly-cosaminoglycans: analysis of the binding site. Biochemistry 1998;37:10,643–10,652.

    Article  PubMed  CAS  Google Scholar 

  64. Whisstock JC, Pike RN, Jin L, et al. Conformational changes in serpins: II. The mechanism of activation of antithrombin by heparin. J Mol Biol 2000;301:1287–1305.

    Article  PubMed  CAS  Google Scholar 

  65. Maik-Rachline G, Shaltiel S, Seger R. Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor. Blood 2005;105:670–678.

    Article  PubMed  CAS  Google Scholar 

  66. Pike RN, Bottomley SP, Irving JA, Bird PI, Whisstock JC. Serpins: finely balanced confor-mational traps. IUBMB Life 2002;54:1–7.

    Article  PubMed  CAS  Google Scholar 

  67. Lomas DA, Carrell RW. Serpinopathies and the conformational dementias. Nat Rev Genet 2004;3:759–768.

    Article  CAS  Google Scholar 

  68. Wu YQ, Becerra SP. Proteolytic activity directed toward pigment epithelium-derived factor in vitreous of bovine eyes. Implications of proteolytic processing. Invest Ophthalmol Vis Sci 1996;37:1984–1993.

    PubMed  CAS  Google Scholar 

  69. Eichler W, Yafai Y, Wiedemann P, Reichenbach A. Angiogenesis-related factors derived from retinal glial (Muller) cells in hypoxia. Neuroreport 2004;15:1633–1637.

    Article  PubMed  CAS  Google Scholar 

  70. Stitt AW, Graham D, Gardiner TA. Ocular wounding prevents pre-retinal neovascularization and upregulates PEDF expression in the inner retina. Mol Vis 2004;10:432–438.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Missouri-Kansas City, Kansas City, MO

    Joyce Tombran-Tink PhD

  2. Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT

    Joyce Tombran-Tink PhD & Colin J. Barnstable DPhil

Authors
  1. Joyce Tombran-Tink PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Colin J. Barnstable DPhil
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, MO

    Joyce Tombrain-Tink PhD

  2. Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT

    Joyce Tombrain-Tink PhD  & Colin J. Barnstable DPhil  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Tombran-Tink, J., Barnstable, C.J. (2006). Control of Neovascularization and Cell Survival in the Eye by PEDF. In: Tombrain-Tink, J., Barnstable, C.J. (eds) Ocular Angiogenesis. Opthalmology Research. Humana Press. https://doi.org/10.1007/978-1-59745-047-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-047-8_13

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-514-9

  • Online ISBN: 978-1-59745-047-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation