Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny

Alexandra Beaudry-Richard, Mathieu Nadeau-Vallée, Élizabeth Prairie, Noémie Maurice, Émilie Heckel, Mohammad Nezhady, Sheetal Pundir, Ankush Madaan, Amarilys Boudreault, Xin Hou, Christiane Quiniou, Estefania Marin Sierra, Alexandre Beaulac, Gregory Lodygensky, Sarah A. Robertson, Jeffrey Keelan, Kristina Adams-Waldorf, David M. Olson, Jose Carlos Rivera, William D. LubellJean Sebastien Joyal, Jean François Bouchard, Sylvain Chemtob

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Abstract

Antenatal inflammation as seen with chorioamnionitis is harmful to foetal/neonatal organ development including to eyes. Although the major pro-inflammatory cytokine IL-1β participates in retinopathy induced by hyperoxia (a predisposing factor to retinopathy of prematurity), the specific role of antenatal IL-1β associated with preterm birth (PTB) in retinal vasculopathy (independent of hyperoxia) is unknown. Using a murine model of PTB induced with IL-1β injection in utero, we studied consequent retinal and choroidal vascular development; in this process we evaluated the efficacy of IL-1R antagonists. Eyes of foetuses exposed only to IL-1β displayed high levels of pro-inflammatory genes, and a persistent postnatal infiltration of inflammatory cells. This prolonged inflammatory response was associated with: (1) a marked delay in retinal vessel growth; (2) long-lasting thinning of the choroid; and (3) long-term morphological and functional alterations of the retina. Antenatal administration of IL-1R antagonists – 101.10 (a modulator of IL-1R) more so than Kineret (competitive IL-1R antagonist) – prevented all deleterious effects of inflammation. This study unveils a key role for IL-1β, a major mediator of chorioamnionitis, in causing sustained ocular inflammation and perinatal vascular eye injury, and highlights the efficacy of antenatal 101.10 to suppress deleterious inflammation.

Original languageEnglish
Article number11875
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 8 Aug 2018

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    Beaudry-Richard, A., Nadeau-Vallée, M., Prairie, É., Maurice, N., Heckel, É., Nezhady, M., ... Chemtob, S. (2018). Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny. Scientific Reports, 8(1), [11875]. https://doi.org/10.1038/s41598-018-30087-4