Skip to main content

The Role of Fibroblast Growth Factors in Ocular Angiogenesis

  • Chapter
Ocular Angiogenesis

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

  • 882 Accesses

Abstract

The eye is a highly vascularized organ that possesses two vascular networks in the adult, the retinal vessels and the choroid vessels, as well as a transitory vascular system, the hyaloid vessels, which regress in vertebrates after birth. Abnormal vessel growth is observed in a number of ocular pathologies such as retinopathy or age-related macular dystrophy. Studies on the molecular mechanisms of eye vascularization have demonstrated a central role of vascular endothelial growth factor (VEGF) family members in these processes (15). Other molecular players, such as angiopoietins, seem to be implicated in the remodeling of retinal vessels (6).

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 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. Gariano RF. Cellular mechanisms in retinal vascular development. Prog Retin Eye Res 2003;22:295–306.

    Article  PubMed  CAS  Google Scholar 

  2. Provis JM. Development of the primate retinal vasculature. Prog Retin Eye Res 2001;20:799–821.

    Article  PubMed  CAS  Google Scholar 

  3. Provis JM, Leech J, Diaz CM, Penfold PL, Stone J, Keshet E. Development of the human retinal vasculature: cellular relations and VEGF expression. Exp Eye Res 1997;65:555–568.

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Campochiaro PA, Hackett SF. Ocular neovascularization: a valuable model system. Oncogene 2003;22:6537–6548.

    Article  PubMed  CAS  Google Scholar 

  6. Uemura A, Ogawa M, Hirashima M, et al. Recombinant angiopoietin-1 restores higherorder architecture of growing blood vessels in mice in the absence of mural cells. J Clin Invest 2002;110:1619–1628.

    Article  PubMed  CAS  Google Scholar 

  7. Bikfalvi A, Klein S, Pintucci G, Rifkin DB. Biological roles of fibroblast growth factor-2. EndocrRev 1997;18:26–45.

    Article  CAS  Google Scholar 

  8. Javerzat S, Auguste P, Bikfalvi A. The role of fibroblast growth factors in vascular development. Trends Mol Med 2002;8:483–489.

    Article  PubMed  CAS  Google Scholar 

  9. Auguste P, Javerzat S, Bikfalvi A. Regulation of vascular development by fibroblast growth factors. Cell Tissue Res 2003;314:157–166.

    Article  PubMed  CAS  Google Scholar 

  10. Gerwins P, Skoldenberg E, Claesson-Welsh L. Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis. Crit Rev Oncol Hematol 2000;34:185–194.

    Article  PubMed  CAS  Google Scholar 

  11. Klein S, Bikfalvi A, Birkenmeier TM, Giancotti FG, Rifkin DB. Integrin regulation by endogenous expression of 18-kDa fibroblast growth factor-2. J Biol Chem 1996;271:22,583–22,590.

    Article  PubMed  CAS  Google Scholar 

  12. Hood JD, Frausto R, Kiosses WB, Schwartz MA, Cheresh DA. Differential alphav integrinmediated Ras-ERK signaling during two pathways of angiogenesis. J Cell Biol 2003; 162:933–943.

    Article  PubMed  CAS  Google Scholar 

  13. Pepper MS. Extracellular proteolysis and angiogenesis. Thromb Haemost 2001;86:346–355.

    PubMed  CAS  Google Scholar 

  14. Counis MF, Chaudun E, Arruti C, et al. Analysis of nuclear degradation during lens cell differentiation. Cell Death Differ 1998;5:251–261.

    Article  PubMed  CAS  Google Scholar 

  15. Bryckaert M, Guillonneau X, Hecquet C, Perani P, Courtois Y, Mascarelli F. Regulation of proliferation-survival decisions is controlled by FGF1 secretion in retinal pigmented epithelial cells. Oncogene 2000; 19:4917–4929.

    Article  PubMed  CAS  Google Scholar 

  16. Russell C. The roles of hedgehogs and fibroblast growth factors in eye development and retinal cell rescue. Vision Res 2003;43:899–912.

    Article  PubMed  CAS  Google Scholar 

  17. Chaum E. Retinal neuroprotection by growth factors: a mechanistic perspective. J Cell Biochem 2003;88:57–75.

    Article  PubMed  CAS  Google Scholar 

  18. Fruttiger M. Development of the mouse retinal vasculature: angiogenesis versus vasculogenesis. Invest Ophthalmol Vis Sci 2002;43:522–527.

    PubMed  Google Scholar 

  19. Gerhardt H, Golding M, Fruttiger M, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 2003;161:1163–1177.

    Article  PubMed  CAS  Google Scholar 

  20. Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 2002;64:993–998.

    Article  PubMed  CAS  Google Scholar 

  21. Masson N, Ratcliffe PJ. HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular 0(2) levels. J Cell Sci 2003;l16:3041–3049.

    Article  Google Scholar 

  22. Stone J, Itin A, Alon T, et al. Development of retinal vasculature is mediated by hypoxiainduced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 1995;15:4738–4747.

    PubMed  CAS  Google Scholar 

  23. Chan-Ling T, McLeod DS, Hughes S, et al. Astrocyte-endothelial cell relationships during human retinal vascular development. Invest Ophthalmol Vis Sci 2004;45:2020–2032.

    Article  PubMed  Google Scholar 

  24. Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, Friedlander M. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med 2002;8:1004–1010.

    Article  PubMed  CAS  Google Scholar 

  25. Guillonneau X, Bryckaert M, Launay-Longo C, Courtois Y. Endogenous FGF1-induced activation and synthesis of extracellular signal-regulated kinase 2 reduce cell apoptosis in retinal-pigmented epithelial cells. J Biol Chem 1998;273:22,367–22,373.

    Article  PubMed  CAS  Google Scholar 

  26. Mousa SA, Lorelli W, Campochiaro PA. Role of hypoxia and extracellular matrix-integrin binding in the modulation of angiogenic growth factors secretion by retinal pigmented epithelial cells. J Cell Biochem 1999;74:135–143.

    Article  PubMed  CAS  Google Scholar 

  27. Alizadeh M, Miyamura N, Handa JT, Hjelmeland LM. Human RPE cells express the FGFR2IIIc and FGFR3IIIc splice variants and FGF9 as a potential high affinity ligand. Exp Eye Res 2003;76:249–256.

    Article  PubMed  CAS  Google Scholar 

  28. Hayashi T, Mizuno N, Ueda Y, Okamoto M, Kondoh H. FGF2 triggers iris-derived lens regeneration in newt eye. Mech Dev 2004;121:519–526.

    Article  PubMed  CAS  Google Scholar 

  29. Wada M, Gelfman CM, Matsunaga H, et al. Density-dependent expression of FGF-2 in response to oxidative stress in RPE cells in vitro. Curr Eye Res 2001;23:226–231.

    Article  PubMed  CAS  Google Scholar 

  30. Walsh N, Valter K, Stone J. Cellular and subcellular patterns of expression of bFGF and CNTF in the normal and light stressed adult rat retina. Exp Eye Res 2001;72:495–501.

    Article  PubMed  CAS  Google Scholar 

  31. Martin G, Schlunck G, Hansen LL, Agostini HT. Differential expression of angioregulatory factors in normal and CNV-derived human retinal pigment epithelium. Graefes Arch Clin Exp Ophthalmol 2004;242:321–326.

    Article  PubMed  CAS  Google Scholar 

  32. Zhang L, El-Hodiri HM, Ma HF, et al. Targeted expression of the dominant-negative FGFR4a in the eye using XrxlA regulatory sequences interferes with normal retinal development. Development 2003;130:4177–4186.

    Article  PubMed  CAS  Google Scholar 

  33. Valter K, van Driel D, Bisti S, Stone J. FGFR1 expression and FGFR1-FGF-2 colocalisation in rat retina: sites of FGF-2 action on rat photoreceptors. Growth Factors 2002;20:177–188.

    Article  PubMed  CAS  Google Scholar 

  34. Matsushima M, Ogata N, Takada Y, et al. FGF receptor 1 expression in experimental choroidal neovascularization. Jpn J Ophthalmol 1996;40:329–338.

    PubMed  CAS  Google Scholar 

  35. Gu X, El-Remessy AB, Brooks SE, Al-Shabrawey M, Tsai NT, Caldwell RB. Hyperoxia induces retinal vascular endothelial cell apoptosis through formation of peroxynitrite. Am J Physiol Cell Physiol 2003;285:546–554.

    Google Scholar 

  36. Lee SH, Schloss DJ, Swain JL. Maintenance of vascular integrity in the embryo requires signaling through the fibroblast growth factor receptor. J Biol Chem 2000;275:33,679–33,687.

    Article  PubMed  CAS  Google Scholar 

  37. Soubrane G, Cohen SY, Delayre T, et al. Basic fibroblast growth factor experimentally induced choroidal angiogenesis in the minipig. Curr Eye Res 1994; 13:183–195.

    PubMed  CAS  Google Scholar 

  38. Cao R, Brakenhielm E, Pawliuk R, et al. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nat Med 2003;9:604–613.

    Article  PubMed  CAS  Google Scholar 

  39. Tobe T, Ortega S, Luna JD, et al. Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model. Am J Pathol 1998; 15:1641–1666.

    Google Scholar 

  40. Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol 2, REVIEWS3005.

    Google Scholar 

  41. Rousseau B, Dubayle D, Sennlaub F, et al. Neural and angiogenic defects in eyes of transgenic mice expressing a dominant-negative FGF receptor in the pigmented cells. Exp Eye Res 2000;71:395–404.

    Article  PubMed  CAS  Google Scholar 

  42. Rousseau B, Larrieu-Lahargue F, Bikfalvi A, Javerzat S. Involvement of fibroblast growth factors in choroidal angiogenesis and retinal vascularization. Exp Eye Res 2003;77:147–156.

    Article  PubMed  CAS  Google Scholar 

  43. Hackett SF, Wiegand S, Yancopoulos G, Campochiaro PA. Angiopoietin-2 plays an important role in retinal angiogenesis. J Cell Physiol 2002; 192:182–187.

    Article  PubMed  CAS  Google Scholar 

  44. Zubilewicz A, Hecquet C, Jeanny JC, Soubrane G, Courtois Y, Mascarelli F. Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: a comparative study with VEGF. Oncogene 2001;20:1403–1413.

    Article  PubMed  CAS  Google Scholar 

  45. Yamada H, Yamada E, Kwak N, et al. Cell injury unmasks a latent proangiogenic phenotype in mice with increased expression of FGF2 in the retina. J Cell Physiol 2000;185:135–142.

    Article  PubMed  CAS  Google Scholar 

  46. Rousseau B, Larrieu-Lahargue F, Javerzat S, Guilhem-Ducleon F, Beermann F, Bikfalvi A. The tyrpl-Tag/tyrpl-FGFRl-DN bigenic mouse: a model for selective inhibition of tumor development, angiogenesis, and invasion into the neural tissue by blockade of fibroblast growth factor receptor activity. Cancer Res 2004;64:2490–2495.

    Article  PubMed  CAS  Google Scholar 

  47. Lubarsky B, Krasnow MA. Tube morphogenesis: making and shaping biological tubes. Cell 2003; 112:19–28.

    Article  PubMed  CAS  Google Scholar 

  48. Li J, Shworak NW, Simons M. Increased responsiveness of hypoxic endothelial cells to FGF2 is mediated by HIF-lalpha-dependent regulation of enzymes involved in synthesis of heparan sulfate FGF2-binding sites. J Cell Sci 2002; 115:1951–1959.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Bikfalvi, A., Javerzat, S. (2006). The Role of Fibroblast Growth Factors in Ocular Angiogenesis. In: Tombrain-Tink, J., Barnstable, C.J. (eds) Ocular Angiogenesis. Opthalmology Research. Humana Press. https://doi.org/10.1007/978-1-59745-047-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-047-8_12

  • 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