IL-1β induces rod degeneration through the disruption of retinal glutamate homeostasis - Sorbonne Université
Journal Articles Journal of Neuroinflammation Year : 2020

IL-1β induces rod degeneration through the disruption of retinal glutamate homeostasis

Lucile Vignaud
  • Function : Author
  • PersonId : 1029534
Nour Barmo
  • Function : Author
Serge Picaud
Xavier Guillonneau

Abstract

Background: Age-related macular degeneration is characterized by the accumulation of subretinal macrophages and the degeneration of cones, but mainly of rods. We have previously shown that Mononuclear Phagocytes-derived IL-1β induces rod photoreceptor cell death during experimental subretinal inflammation and in retinal explants exposed to IL-1β but the mechanism is unknown. Methods: Retinal explants were culture in the presence of human monocytes or IL-1β and photoreceptor cell survival was analyzed by TUNEL labeling. Glutamate concentration and transcription levels of gene involved in the homeostasis of glutamate were analyzed in cell fractions of explant cultured or not in the presence of IL-1β. Glutamate receptor antagonists were evaluated for their ability to reduce photoreceptor cell death in the presence of IL1-β or monocytes. Results: We here show that IL-1β does not induce death in isolated photoreceptors, suggesting an indirect effect. We demonstrate that IL-1β leads to glutamate-induced rod photoreceptor cell death as it increases the extracellular glutamate concentrations in the retina through the inhibition of its conversion to glutamine in Müller cells, increased release from Müller cells, and diminished reuptake. The inhibition of non-NMDA receptors completely and efficiently prevented rod apoptosis in retinal explants cultured in the presence of IL-1β or, more importantly, in vivo, in a model of subretinal inflammation. Conclusions: Our study emphasizes the importance of inflammation in the deregulation of glutamate homeostasis and provides a comprehensive mechanism of action for IL-1β-induced rod degeneration.
Fichier principal
Vignette du fichier
document.pdf (5.06 Mo) Télécharger le fichier
Origin Publication funded by an institution
Loading...

Dates and versions

hal-02492176 , version 1 (26-02-2020)

Identifiers

Cite

Hugo Charles-Messance, Guillaume Blot, Aude Couturier, Lucile Vignaud, Sara Touhami, et al.. IL-1β induces rod degeneration through the disruption of retinal glutamate homeostasis. Journal of Neuroinflammation, 2020, 17 (1), pp.1. ⟨10.1186/s12974-019-1655-5⟩. ⟨hal-02492176⟩
85 View
50 Download

Altmetric

Share

More