PURPOSE: The purpose of this study was to evaluate the inhibitory effects of the nanoparticle-mediated delivery of plasminogen kringle 5 (K5) on choroidal neovascularization (CNV) and retinal inflammation. METHODS: CNV was induced by laser in adult rats. Nanoparticles with an expression plasmid of K5 (K5-NP) were injected into the vitreous. K5 expression was detected by immunohistochemistry. The CNV area was measured after fluorescein angiography. Retinal vascular permeability was quantified with Evans blue as a tracer. Expression of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 was measured by Western blot analysis or ELISA and real-time RT-PCR. RESULTS: Intense K5 expression was detected in the retina 2 weeks after the injection of K5-NP. Areas of CNV were significantly decreased in the K5-NP treatment group compared with that in the control-NP group. The K5-NP injection also significantly reduced vascular permeability. The expression of VEGF was downregulated by K5-NP at both the protein and mRNA levels. Moreover, K5-NP also inhibited expression of TNF-α and ICAM-1. Similarly, K5-NP decreased retinal levels of total β-catenin. In cultured cells, K5-NP suppressed hypoxia-induced secretion of MCP-1 and TNF-α. CONCLUSIONS: K5 has a novel anti-inflammatory activity. K5-NP mediates a sustained inhibitory effect on CNV and thus has therapeutic potential for age-related macular degeneration.
PURPOSE: The purpose of this study was to evaluate the inhibitory effects of the nanoparticle-mediated delivery of plasminogen kringle 5 (K5) on choroidal neovascularization (CNV) and retinal inflammation. METHODS: CNV was induced by laser in adult rats. Nanoparticles with an expression plasmid of K5 (K5-NP) were injected into the vitreous. K5 expression was detected by immunohistochemistry. The CNV area was measured after fluorescein angiography. Retinal vascular permeability was quantified with Evans blue as a tracer. Expression of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 was measured by Western blot analysis or ELISA and real-time RT-PCR. RESULTS: Intense K5 expression was detected in the retina 2 weeks after the injection of K5-NP. Areas of CNV were significantly decreased in the K5-NP treatment group compared with that in the control-NP group. The K5-NP injection also significantly reduced vascular permeability. The expression of VEGF was downregulated by K5-NP at both the protein and mRNA levels. Moreover, K5-NP also inhibited expression of TNF-α and ICAM-1. Similarly, K5-NP decreased retinal levels of total β-catenin. In cultured cells, K5-NP suppressed hypoxia-induced secretion of MCP-1 and TNF-α. CONCLUSIONS:K5 has a novel anti-inflammatory activity. K5-NP mediates a sustained inhibitory effect on CNV and thus has therapeutic potential for age-related macular degeneration.
Authors: Don J Davidson; Catherine Haskell; Sandy Majest; Abdullah Kherzai; David A Egan; Karl A Walter; Andrew Schneider; Earl F Gubbins; Larry Solomon; Zhebo Chen; Rick Lesniewski; Jack Henkin Journal: Cancer Res Date: 2005-06-01 Impact factor: 12.701
Authors: H Lu; M Dhanabal; R Volk; M J Waterman; R Ramchandran; B Knebelmann; M Segal; V P Sukhatme Journal: Biochem Biophys Res Commun Date: 1999-05-19 Impact factor: 3.575
Authors: L E Smith; E Wesolowski; A McLellan; S K Kostyk; R D'Amato; R Sullivan; P A D'Amore Journal: Invest Ophthalmol Vis Sci Date: 1994-01 Impact factor: 4.799
Authors: Neil M Bressler; Susan B Bressler; Nathan G Congdon; Frederick L Ferris; David S Friedman; Ronald Klein; Anne S Lindblad; Roy C Milton; Johanna M Seddon Journal: Arch Ophthalmol Date: 2003-11
Authors: L P Aiello; R L Avery; P G Arrigg; B A Keyt; H D Jampel; S T Shah; L R Pasquale; H Thieme; M A Iwamoto; J E Park Journal: N Engl J Med Date: 1994-12-01 Impact factor: 91.245
Authors: Xiaoping Qi; Jun Cai; Qing Ruan; Li Liu; Sanford L Boye; Zhijuan Chen; William W Hauswirth; Renee C Ryals; Lynn Shaw; Sergio Caballero; Maria B Grant; Michael E Boulton Journal: Invest Ophthalmol Vis Sci Date: 2012-02-01 Impact factor: 4.799
Authors: Haijiang Lin; Yueran Yue; Daniel E Maidana; Peggy Bouzika; Alp Atik; Hidetaka Matsumoto; Joan W Miller; Demetrios G Vavvas Journal: Semin Ophthalmol Date: 2016 Impact factor: 1.975