June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Anti-VEGF therapy inhibits microglial activation and migration in the retina
Author Affiliations & Notes
  • Aude Couturier
    ophthalmology, Hopital Lariboisière, Université Paris Diderot-Sorbonne Paris Cité, APHP, Paris, France
    UMRS 872 Physiopathology of ocular diseases: therapeutic innovations, INSERM, Paris, France
  • Elodie Bousquet
    UMRS 872 Physiopathology of ocular diseases: therapeutic innovations, INSERM, Paris, France
  • Min Zhao
    UMRS 872 Physiopathology of ocular diseases: therapeutic innovations, INSERM, Paris, France
  • Brigitte Goldenberg
    UMRS 872 Physiopathology of ocular diseases: therapeutic innovations, INSERM, Paris, France
  • Yvonne De Kozak
    UMRS 872 Physiopathology of ocular diseases: therapeutic innovations, INSERM, Paris, France
  • Francine Behar-Cohen
    UMRS 872 Physiopathology of ocular diseases: therapeutic innovations, INSERM, Paris, France
    Ophthalmology, Hopital Hotel Dieu, Université Paris Descartes, APHP, Paris, France
  • Footnotes
    Commercial Relationships Aude Couturier, None; Elodie Bousquet, None; Min Zhao, None; Brigitte Goldenberg, None; Yvonne De Kozak, None; Francine Behar-Cohen, Inserm/Univesrité ParisDescartes (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5598. doi:https://doi.org/
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 595 microglia • 748 vascular endothelial growth factor • 746 uveitis-clinical/animal model  
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