Purchase this article with an account.
K. Park, Y. Chen, A. Mayo, U. Kompella, Y. Hu, R. Longeras, J.-X. Ma; Effect of Nanoparticle-Mediated K5 Gene Delivery on Ischemia-Induced Retinal Neovascularization and Vascular Leakage. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4970.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinal vascular leakage and neovascularization (NV) are common complications in many ocular disorders such as diabetic retinopathy. Previous studies showed that plasminogen kringle 5 (K5), a fragment of plasminogen, inhibits retinal NV and reduces retinal vascular leakage. The purpose of this project was to demonstrate the K5 expression and vascular effects from nanoparticle-mediated K5 gene delivery.
An expression plasmid of K5 was encapsulated with poly lactide-co-glycolic acid (PLGA) to form K5 nanoparticles (K5-NP). The expression and function of K5 were determined in vitro using ARPE19, a human cell line derived from retinal pigment epithelium (RPE) and primary bovine retinal capillary endothelial cells (BRCEC) and in vivo using oxygen-induced retinopathy (OIR) rats. K5 expression was detected by Western blot analysis and immunohistochemistry. K5 effect on cell viability was determined by MTT assay. VEGF levels were measured by ELISA. The in vivo effect of K5-NP was determined in OIR rats using vascular permeability assay and fluorescein retinal angiography.
K5 was expressed and secreted from ARPE19 cells treated with K5-NP but not from the cells treated with Control-NP. Moreover, the K5-NP treatment inhibited growth of BRCEC but not ARPE19 cells. K5-NP treatment also blocked VEGF over-expression induced by hypoxia in ARPE19 cells. An intravitreal injection of K5-NP resulted in substantial expression of K5 in the inner retina. The injection of K5-NP significantly reduced retinal vascular leakage in OIR rats, when compared to the contralateral eyes injected with Control-NP. Moreover, the K5-NP injection effectively ameliorated retinal NV in OIR rats.
Nanoparticles mediate efficient K5 expression in vitro and in vivo and have therapeutic potential in retinal vascular leakage and retinal NV.
This PDF is available to Subscribers Only