The Rat and the Rabbit Cornea Assay

  • Lucia Morbidelli
  • Marina Ziche
Part of the NATO ASI Series book series (NSSA, volume 298)


In order to develop angiogenic and antiangiogenic strategies, there are concerted efforts to provide animal model for more quantitative analysis of in vivo angiogenesis. In vivo techniques consist in the rat and rabbit cornea assay, the sponge implant assay, the fibrin clots, sodium alginate beads and matrigel plugs and the chick embryo chorioallantoic membrane. In this chapter we will discuss on the avascular cornea assay and the advantages and divadvantages in the rat and the rabbits, the two animal species most used.


Angiogenic Response Vascular Endothelial Cell Growth Factor Corneal Neovascularization Rabbit Cornea Matrigel Plug 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albini, A., R. Benelli, M. Presta, M. Rusnati, M. Ziche, A. Rubartelli, G. Paglialunga, F. Bussolino and D. Noonan. HIV-tat protein is a heparin-binding angiogenic growth factor. Oncogene, 12: 289–297, 1996.PubMedGoogle Scholar
  2. Bussolino, F., M. Ziche, J. M. Wang, D. Alessi, L. Morbidelli, O. Cremona, A. Bosia, P. Marchisio and A. Mantovani. In vitro and in vivo activation of endothelial cells by colony-stimulating factors. J. Clin. Invest., 87: 986–995, 1991.PubMedCrossRefGoogle Scholar
  3. Bussolino, F., M.F. Di Renzo, M. Ziche, E. Bocchietto, M. Oliviero, L. Naldini, G. Gaudino, L. Tamagnone, A. Coffer, P.C. Marchisio and P.M. Comoglio. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J. Cell Biol., 119(3): 629–641, 1992.PubMedCrossRefGoogle Scholar
  4. Choudhuri, R., H.-T. Zhang, S. Donnini, M. Ziche and R. Bicknell. An angiogenic role for the neurotrophins midkine and pleiotrophin in tumorigenesis. Cancer Res., 57: 1814–1819, 1997.PubMedGoogle Scholar
  5. Coltrini, D., A. Gualandris, E.M. Nelli, S. Parolini, M.P. Molinari-Tosatti, N. Quarto, M. Ziche, R. Giavazzi and M. Presta. Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-l-B cells: an export- dependent mechanism of action. Cancer Res. 55: 4729–4738, 1995.PubMedGoogle Scholar
  6. Conrad, T.J., D.B. Chandler, J.M. Corless and G.K. Klintworth. In vivo measurement of corneal angiogenesis with video data acquisition and computerized image analysis. Lab. Invest., 70: 426–434, 1994.PubMedGoogle Scholar
  7. Gimbrone, M. Jr., R. Cotran, S.B. Leapman, and J. Folkman. Tumor growth and neovascularization: An experimental model using the rabbit cornea. J. Natl. Cancer Inst. 52: 413–427, 1974.PubMedGoogle Scholar
  8. Gualandris, A., M. Rusnati, M. Belleri, E.M. Nelli, M. Bastaki, M.P. Molinari-Tosatti, F. Bonardi, S. Parolini, A. Albini, L. Morbidelli, M. Ziche, A. Corallini, L. Possati, A. Vacca, D. Ribatti, and M. Presta. Basic fibroblast growth factor overexpression in mouse endothelial cells: an autocrine model of angiogenesis and angioproliferative diseases. Cell Growth Differentiation 7: 147–160, 1996.PubMedGoogle Scholar
  9. Langer, R., and J. Folkman. Polymers for the sustained release of proteins and other macromolecules. Nature 363: 797–800, 1976.CrossRefGoogle Scholar
  10. Polverini, P.J., and S.J. Leibovich. Induction of neovascularization in vivo and endothelial cell proliferation in vitro by tumor associated macrophages. Lab. Invest., 51: 635–642, 1984PubMedGoogle Scholar
  11. Proia, A.D., D.B. Chadler, W.L. Haynes, C.F. Smith, C. Suvarenamani, F.H. Erkel and G.K. Klintworth. Quantification of corneal neovascularization using computerized image analysis. Lab. Invest., 58: 473–479, 1988.PubMedGoogle Scholar
  12. Zhang H.T., P. Kraft, P.A.E. Scott, M. Ziche, H.A. Weich, A.L. Harris and R. Bicknell. Enhancement of tumour growth and vascular density by transfection of vascular endothelial cell growth factor (VEGF) into MCF7 human breast carcinoma cells. J. Natl. Cancer Inst., 87 (3): 213–219, 1995.PubMedCrossRefGoogle Scholar
  13. Ziche, M. and P.M. Gullino. Angiogenesis and neoplastic progression in vitro. J. Natl. Cancer Inst., 69: 483–487, 1982.PubMedGoogle Scholar
  14. Ziche, M., D. Maglione, D. Ribatti, L. Morbidelli, C.T. Lago, M. Battisti, I. Paoletti, A. Barra, M. Tucci, G. Parise, V. Vincenti, H.J. Granger, G Viglietto, and G.M. Persico. Placenta growth factor-1 (PlGF-1) is chemotactic, mitogenic and angiogenic. Lab. Invest, 76: 517–531, 1997(a).PubMedGoogle Scholar
  15. Ziche, M., G. Alessandri, and P.M. Gullino. Gangliosides promote the angiogenic response. Lab. Invest., 61: 629–634, 1989.PubMedGoogle Scholar
  16. Ziche, M., G. Gasparini, R. Choudhuri, R. Bicknell, L. Morbidelli, A. Parenti and F. Ledda. Antiangiogenic effect of Linomide on breast cancer VEGF transfectants. Oncology Report, 4: 253–256, 1997 (b).Google Scholar
  17. Ziche, M., J. Jones, and P.M. Gullino. Role of prostaglandinE1 and copper in angiogenesis. J. Natl. Cancer Inst., 69: 475–482, 1982.PubMedGoogle Scholar
  18. Ziche, M., L. Morbidelli, E. Masini, S. Amerini, H.J. Granger, CA. Maggi, P. Geppetti and F. Ledda. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by Substance P. J. Clin. Invest., 94: 2036–2044, 1994.PubMedCrossRefGoogle Scholar
  19. Ziche, M., L. Morbidelli, M. Pacini, P. Geppetti, G. Alessandri and C.A. Maggi. Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells. Microvasc. Res., 40: 264–278, 1990.PubMedCrossRefGoogle Scholar
  20. Ziche, M., L. Morbidelli, R. Choudhuri, H.-T. Zhang, S. Donnini, H.J. Granger and R. Bicknell. Nitric oxide-synthase lies downstream of Vascular Endothelial Growth Factor but not basic Fibroblast Growth Factor induced angiogenesis. J. Clin. Invest., 99: 2625–2634, 1997 (c).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Lucia Morbidelli
    • 1
  • Marina Ziche
    • 1
  1. 1.Dept. PharmacologyUniversity of FlorenceFlorenceItaly

Personalised recommendations