Diabetologia

, Volume 44, Issue 6, pp 757–765 | Cite as

Intravitreal injection of plasminogen kringle 5, an endogenous angiogenic inhibitor, arrests retinal neovascularization in rats

  • D. Zhang
  • P. L. Kaufman
  • G. Gao
  • R. A. Saunders
  • J. X. Ma
Article

Abstract

Aims/hypothesis. Plasminogen kringle 5 is an endogenous angiogenic inhibitor. The purpose of the present study was to explore the potential application of kringle 5 in the treatment of retinal neovascularization. Methods. Plasminogen kringle 5 was expressed in E. coli and affinity-purified. Its anti-angiogenic activity was determined in cultured primary human capillary endothelial cells. Retinal neovascularization was induced in newborn rats by exposure to hyperoxia and then normoxia. Kringle 5 was intravitreally injected into the rat model. Retinal neovascularization was visualized by fluorescein angiography on flat-mounted retina and quantified by counting preretinal vascular cells. Results. Plasminogen kringle 5 inhibited primary endothelial cells but not retinal neuronal cells, suggesting cell type-specific inhibition. The oxygen-induced retinopathy rat model showed an over-expression of vascular endothelial growth factor, preretinal neovascularization and haemorrhage. Intravitreal injection of kringle 5 before the development of neovascularization resulted in fewer neovascular tufts and pre-retinal vascular cells than in control rats with PBS injection (p < 0.01). Moreover, injection of kringle 5 after the development of neovascularization inhibited the increase in the preretinal vascular cells (p < 0.05). These results suggest that kringle 5 both prevents the development and arrests the progression of retinal neovascularization. The injection of kringle 5 did not result in any detectable inflammatory response in the retina or histological toxicity to retina neurons and pre-existing vessels. Conclusion/interpretation. These observations suggest that intravitreal delivery of angiogenic inhibitors could have therapeutic benefits in neovascular diseases of the retina. [Diabetologia (2001) 44: 757–765]

Keywords Angiogenesis angiogenic inhibitor angiostatin diabetes retinopathy of prematurity. 

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • D. Zhang
    • 1
  • P. L. Kaufman
    • 1
  • G. Gao
    • 1
  • R. A. Saunders
    • 1
  • J. X. Ma
    • 1
  1. 1.Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USAUS

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