April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
A Novel Modulator of the IL-1 Receptor Prevents Development of Oxygen-Induced Retinopathy
Author Affiliations & Notes
  • J. C. Rivera
    Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste-Justine, Research Center, Montreal, Quebec, Canada
  • P. Sapieha
    Department of Ophthalmology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts
  • J. C. Honore
    Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste-Justine, Research Center, Montreal, Quebec, Canada
  • D. Hamel
    Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste-Justine, Research Center, Montreal, Quebec, Canada
  • C. Quiniou
    Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste-Justine, Research Center, Montreal, Quebec, Canada
    Allostera Pharma Inc., Montreal, Quebec, Canada
  • S. Chemtob
    Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste-Justine, Research Center, Montreal, Quebec, Canada
    Allostera Pharma Inc., Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships  J.C. Rivera, None; P. Sapieha, None; J.C. Honore, None; D. Hamel, None; C. Quiniou, None; S. Chemtob, None.
  • Footnotes
    Support  Heart and Stroke Foundation of Canada (HSCF) and the Canadian Stroke Network (CSN)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3336. doi:https://doi.org/
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    • Get Citation

      J. C. Rivera, P. Sapieha, J. C. Honore, D. Hamel, C. Quiniou, S. Chemtob; A Novel Modulator of the IL-1 Receptor Prevents Development of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3336. doi: https://doi.org/.

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

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Abstract

Purpose: : Retinopathy of prematurity (ROP), is associated with generation of inflammatory mediators. In this context, interleukin-1β (IL-1β) is an established prominent cytokine. IL-1 receptor antagonist (Kineret) is a large protein and the only clinically available inhibitor of IL-1β. Our laboratory developed a novel small allosteric modulator of IL-1 receptor, labelled 101.10 (Quiniou et al, J Immunol, 2008). We investigated whether inhibiting the actions of IL-1β using 101.10 prevented the vaso-obliteration and pathological neovascularization associated with oxygen-induced retinopathy (OIR).

Methods: : Vaso-obliteration was induced in Sprague-Dawley rat pups maintained in 80% O2 from postnatal days (P)5 to P10. IL-1β was measured in retinas. 101.10’s ability to curb vaso-obliteration was tested on animals exposed to O2 from P5-P10; while its effects on pre-retinal neovascularization was tested on newborn rats subjected to OIR model (cycling O2 during 14 days [50% and 10%] followed by room air until P18). Animals received 101.10 or vehicle by intraperitoneal (3mg/kg/day) or oral administration (5mg/kg/day) from birth to sacrifice. Neovascularization was evaluated in retinal flat-mounts stained with lectin.

Results: : Retinas from pups exposed to 80% O2 exhibited increased levels of IL-1β at 12, 24 and 48 h post-O2 exposure. Antagonism of IL-1 receptor using intravitreal injection of 101.10 significantly attenuated vaso-obliteration. Intraperitoneal administration of 101.10 efficiently decreased pathological neovascularization compared to vehicle treatment, protection was generally superior to that observed with Kineret. Moreover, orally administered 101.10 was also found to be effective in preventing vaso-obliteration and aberrant pre-retinal neovascularization.

Conclusions: : Results suggest that the major pro-inflammatory cytokine IL-1β is implicated in the pathogenesis of ROP. 101.10, a potent small molecule inhibitor of IL-RI, is a promising therapeutic candidate to help preserve vascular beds and decrease the detrimental angiogenesis associated with ischemic retinopathies.

Keywords: retinopathy of prematurity • inflammation • cytokines/chemokines 
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