Investigative ophthalmology & visual science · 2018
Pathophysiological Role of VEGF on Retinal Edema and Nonperfused Areas in Mouse Eyes With Retinal Vein Occlusion.
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Nishinaka Anri, Inoue Yuki, Fuma Shinichiro, Hida Yoshifumi, Nakamura Shinsuke, Shimazawa Masamitsu, Hara Hideaki
Аннотация
PURPOSE: To determine the relationship between retinal morphologic changes and molecules involved in the changes after anti-VEGF treatment in the retina of retinal vein occlusion (RVO) murine model.
METHODS: The studies were performed on murine RVO model created by laser irradiation of retinal veins. The site of VEGF expression was determined by immunostaining, and the retinal thickness was measured in the images obtained by optical coherence tomography. The levels of VEGF-related and inflammatory factors after an intravitreal injection of anti-VEGF antibody immediately or 7 days after laser irradiation were determined by Western blotting.
RESULTS: The level of VEGF increased in all retinal layers 1 day after laser irradiation, and expression was higher in the partially perfused areas than in the completely nonperfused areas. In eyes with high expression level of VEGF, early administration of anti-VEGF antibody reduced the retinal thickness, and expressions of VEGF and inflammatory factors returned to normal levels. However, the levels of phosphorylated protein kinase B (AKT), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and endothelial nitric oxide synthase (eNOS) were increased by early administration of anti-VEGF antibody. On the other hand, in eyes with low concentration of VEGF, late injection of anti-VEGF antibody induced retinal thinning and the concentrations of phosphorylated AKT, ERK1/2, and eNOS were lower than that in normal group. Furthermore, anti-VEGF antibody lessened the reduction of aquaporin-4.
CONCLUSIONS: These findings indicate that the effect of anti-VEGF antibody is most likely dependent on its effect on the intraocular VEGF levels.
METHODS: The studies were performed on murine RVO model created by laser irradiation of retinal veins. The site of VEGF expression was determined by immunostaining, and the retinal thickness was measured in the images obtained by optical coherence tomography. The levels of VEGF-related and inflammatory factors after an intravitreal injection of anti-VEGF antibody immediately or 7 days after laser irradiation were determined by Western blotting.
RESULTS: The level of VEGF increased in all retinal layers 1 day after laser irradiation, and expression was higher in the partially perfused areas than in the completely nonperfused areas. In eyes with high expression level of VEGF, early administration of anti-VEGF antibody reduced the retinal thickness, and expressions of VEGF and inflammatory factors returned to normal levels. However, the levels of phosphorylated protein kinase B (AKT), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and endothelial nitric oxide synthase (eNOS) were increased by early administration of anti-VEGF antibody. On the other hand, in eyes with low concentration of VEGF, late injection of anti-VEGF antibody induced retinal thinning and the concentrations of phosphorylated AKT, ERK1/2, and eNOS were lower than that in normal group. Furthermore, anti-VEGF antibody lessened the reduction of aquaporin-4.
CONCLUSIONS: These findings indicate that the effect of anti-VEGF antibody is most likely dependent on its effect on the intraocular VEGF levels.
Предметные рубрики MeSH
Angiogenesis InhibitorsAnimalsBlotting, WesternDisease Models, AnimalElectrophoresis, Polyacrylamide GelFluorescein AngiographyIntravitreal InjectionsLaser-Doppler FlowmetryMaleMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Nitric Oxide Synthase Type IIIPapilledemaProto-Oncogene Proteins c-aktRetinaRetinal Vein OcclusionTomography, Optical CoherenceVascular Endothelial Growth Factor A