June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Interleukine-18 promotes endothelial progenitor cells dysfunction through NOTCH-2 inhibition during oxygen-induced retinopathy
Author Affiliations & Notes
  • Ali Riza Nazari
    Universite de Montreal, Montreal, Quebec, Canada
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • michel desjarlais
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Sylvain Chemtob
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
    Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Ali Riza Nazari None; michel desjarlais None; Sylvain Chemtob None
  • Footnotes
    Support  MITAC Elevated and IRSC
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1401. doi:
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    • Get Citation

      Ali Riza Nazari, michel desjarlais, Sylvain Chemtob; Interleukine-18 promotes endothelial progenitor cells dysfunction through NOTCH-2 inhibition during oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1401.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Oxygen-induced retinopathy (OIR) is characterized by an initial key phase of retinal vascular degeneration leading to visual impairment in premature neonates. During revascularization processes, endothelial progenitor cells (EPCs) are mobilized from the bone marrow to participate in vascular repair processes. Because interleukin-18 (IL-18) is a pro-inflammatory cytokine known to participate in the pathogenesis of OIR, this study investigates the potential deleterious role of IL-18 on EPCs function during OIR.

Methods : EPCs were extracted from the bone marrow of pup rats’ and cultivated on fibronectine coated dish with endothelial growth medium for 21 days. They were then subjected to hyperoxia (80% O2) or to IL-18 stimulation (100ng/mL), and/or transfected with siRNA IL-18 to analyze their migratory and vasculogenic ability. PCR and Western Blot were performed to identify the associated molecular mechanism. In vivo, inhibition of NOTCH-2 receptor (using a chemical inhibitor) in healthy pup rats were performed by IP injection (systemic) to study the impact of NOTCH pathway on EPCs mobilization during vascular development by retinal immunostaining.

Results : The results have shown that hyperoxia induce the intracellular expression of IL-18 in EPCs to impair the migratory and vasculogenic activities, leading to EPC dysfunction. In addition, the impairment is associated with reduced expression of the key angiogenic receptor NOTCH-2. In contrast, suppression of IL-18 protects the migratory and vasculogenic functions against hyperoxia by rescuing the expression levels of NOTCH-2. In vivo, to confirm the importance of NOTCH-2 in vascular development, pup rats were treated or not with NOTCH-2 inhibitor. In NOTCH-2 suppressed rat groups, we found retinal and choroidal vascular degeneration associated with lower number of EPCs localized in vessels.

Conclusions : Our results suggest that hyperoxia, a condition associated with OIR, promotes IL-18 expression in EPCs leading to the impairment of their vascular repair functions by reducing the NOTCH pathway. A therapy based on IL-18 suppression could protect EPC’s biological functions and promote retinal revascularisation during OIR.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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