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

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.

• Authors: D Zhang, P L Kaufman, G Gao, R A Saunders, J X Ma
• Journal: Diabetologia (Diabetologia) Vol. 44 Issue 6 Pg. 757-65 (Jun 2001) ISSN: 0012-186X [Print] Germany
• PMID: 11440369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiogenesis Inhibitors
• Oligopeptides
• Peptide Fragments
• Recombinant Proteins
• arginyl-glycyl-aspartic acid
• Plasminogen
• Oxygen

Topics

• Angiogenesis Inhibitors (administration & dosage, pharmacology)
• Animals
• Capillaries (cytology, drug effects)
• Cell Count
• Cells, Cultured
• Endothelium, Vascular (cytology, drug effects)
• Humans
• Hypoxia (pathology)
• Injections
• Kringles
• Neovascularization, Pathologic (pathology, prevention & control)
• Oligopeptides (pharmacology)
• Oxygen
• Peptide Fragments (administration & dosage, metabolism, pharmacology)
• Plasminogen (metabolism)
• Rats
• Rats, Inbred BN
• Rats, Sprague-Dawley
• Recombinant Proteins (administration & dosage, pharmacology)
• Reference Values
• Retina (drug effects, pathology)
• Retinal Diseases (chemically induced)
• Retinal Vessels (drug effects, pathology)
• Vitreous Body