June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
A small molecule inhibitor of interleukin-1 receptor prevents light-induced retinal degeneration by modulating subretinal inflammation
Author Affiliations & Notes
  • Rabah Dabouz
    McGill University, Montreal, Quebec, Canada
    Ophthalmology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
  • Colin Cheng
    McGill University, Montreal, Quebec, Canada
    Ophthalmology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
  • Samy Omri
    Ophthalmology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
  • Jose Carlos Rivera
    Ophthalmology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
  • michel desjarlais
    Ophthalmology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
  • Sylvain Chemtob
    Pediatrics & Pharmacology, Sainte Justine Hospital, Montreal, Quebec, Canada
    Ophthalmology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Rabah Dabouz, None; Colin Cheng, None; Samy Omri, None; Jose Carlos Rivera, None; michel desjarlais, None; Sylvain Chemtob, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1282. doi:
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    • Get Citation

      Rabah Dabouz, Colin Cheng, Samy Omri, Jose Carlos Rivera, michel desjarlais, Sylvain Chemtob; A small molecule inhibitor of interleukin-1 receptor prevents light-induced retinal degeneration by modulating subretinal inflammation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1282.

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

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Abstract

Purpose : To assess the effects of an IL-1 receptor inhibitor, 101.10, in modulating the inflammatory processes and the preservation of photoreceptor integrity in a model of light-induced retinal degeneration.

Methods : CD-1 mice (12-16 weeks) were exposed to blue light-emitting diode (6000 lux at 450nm) for 6 hours and then sacrificed 3 days post-illumination. Mice were intraperitoneally injected 1 hour before light exposure with 101.10 or phosphate-buffered saline and then twice a day until sacrificed. Inflammatory markers (F4/80, NLRP3, caspase-1, and IL-1β) were evaluated by Western blot or immunofluorescence in the mouse retinas. Macrophage-induced photoreceptor death was assessed ex vivo using retinal explants co-cultured with LPS-activated bone marrow-derived macrophages in the presence or absence of 101.10. Photoreceptor cell death was evaluated by TUNEL assay and caspase-3 immunoreactivity. Retinal function was assessed by flash electroretinography.

Results : 101.10 halved blue light-induced F4/80+ mononuclear phagocyte (MP) recruitment to the subretinal space. Co-localization of NLRP3, caspase-1, and IL-1β with F4/80+ MPs was detected in the subretinal space. Additionally, 101.10 prevented inflammasome and caspase-1 activation, and IL-1β formation in BLE. Retinal explants co-cultured with LPS/ATP-activated bone marrow-derived macrophages resulted in a high number of TUNEL-positive photoreceptors, which was significantly reduced by treatment with 101.10. The inhibition of the inflammatory response in vivo by 101.10 reduced caspase-3 immunoreactivity and the number of TUNEL-positive photoreceptors, and preserved retinal function in mice exposed to blue light.

Conclusions : 101.10 attenuates subretinal inflammation and preserves the integrity and function of photoreceptors in a light model of retinal degeneration. Modulation of the IL-1 receptor is a promising strategy for preserving photoreceptor integrity in ocular degenerative diseases.

This is a 2020 ARVO Annual Meeting abstract.

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