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

Aims/hypothesis. Plasminogen kringle 5 is an endogenous angiogenic inhibito r. The purpose of the present study was to explore the potential applicatio n of kringle 5 in the treatment of retinal neovascularization. Methods. Plasminogen kringle 5 was expressed in E. coli and affinity-purifi ed. Its anti-angiogenic activity was determined in cultured primary human c apillary endothelial cells. Retinal neovascularization was induced in newbo rn rats by exposure to hyperoxia and then normoxia. Kringle 5 was intravitr eally injected into the rat model. Retinal neovascularization was visualize d by fluorescein angiography on flat-mounted retina and quantified by count ing preretinal vascular cells. Results. Plasminogen kringle 5 inhibited primary endothelial cells but not retinal neuronal cells, suggesting cell type-specific inhibition. The oxyge n-induced retinopathy rat model showed an over-expression of vascular endot helial growth factor, preretinal neovascularization and haemorrhage. Intrav itreal 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 neova scularization. The injection of kringle 5 did not result in any detectable inflammatory response in the retina or histological toxicity to retina neur ons and pre-existing vessels. Conclusion/interpretation. These observations suggest that intravitreal del ivery of angiogenic inhibitors could have therapeutic benefits in neovascul ar diseases of the retina.