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Aude Couturier, Elodie Bousquet, Min Zhao, Brigitte Goldenberg, Yvonne De Kozak, Francine Behar-Cohen; Anti-VEGF therapy inhibits microglial activation and migration in the retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5598. doi: https://doi.org/.
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In several retinopathies such as diabetic retinopathy, age-related macular degeneration, uveitis, microglial cells become activated and migrate in the subretinal space. The migration and activation of microglia is recognized as a pathogenic event in the retina but the exact molecular events that trigger this activation remain imperfectly understood. Microglial cells were shown to express VEGF receptor 1 (VEGF-R1, Flt-1) and in vitro brain microglia are activated by VEGF. Whether anti-VEGF treatments exert any effects on retinal microglia activation and migration has not been studied. We have evaluated the effect of a specific rat anti-VEGF antibody on migration and activation of rat microglia in an acute model of inflammation, the Endotoxin-Induced-Uveitis (EIU) model.
EIU was induced by footpad lipopolysaccharide injection and eyes received intravitreal injection of anti-VEGF antibody (15 µg/ml) or vehicle at the time of LPS challenge. Analyses were performed 24 hours after LPS injection. Microglial cells activation (round morphology and iNOS expression) and migration were studied by IBA-1 immuno-staining, cytokines production was measured by multiplex analysis in aqueous humor and iNOS expression in the retina was analyzed using QPCR.
Anti VEGF had no effect on the severity of uveitis and it did not decrease the expression of IL6, TNF, IL1, MCP1 or INF. However, as compared to LPS control eyes, anti VEGF significantly reduced activated microglial density in the inner retina (p < 0.001), microglial migration in the outer retina (p < 0.001), and activated microglial density in the choroids (p < 0.05). Expression of iNOS 2 was decreased in the neuroretina after anti-VEGF treatment.
Anti-VEGF therapy induced a strong inhibitory effect on sub retinal microglial migration and on retinal and choroidal microglia activation, that is dissociated with anti-inflammatory effects of anti-VEGF. This result suggests that anti-VEGF treatment may exert beneficial effects on retinal diseases, independently of their vascular effects.
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