Journal article
IL-18 Attenuates Experimental Choroidal Neovascularization as a Potential Therapy for Wet Age-Related Macular Degeneration
Science translational medicine, Vol.6(230), pp.230ra44-230ra44
04/02/2014
DOI: 10.1126/scitranslmed.3007616
PMCID: PMC12016488
PMID: 24695684
Abstract
Age-related macular degeneration (AMD) is the most common form of central retinal blindness globally. Distinct processes of the innate immune system, specifically activation of the NLRP3 inflammasome, have been shown to play a central role in the development of both "dry" and neovascular ("wet") forms of the disease. We show that the inflammatory cytokine interleukin-18 (IL-18) can regulate choroidal neovascularization formation in mice. We observed that exogenous administration of mature recombinant IL-18 has no effect on retinal pigment epithelial (RPE) cell viability, but that overexpression of pro-IL-18 or pro-IL-1 beta alone can cause RPE cell swelling and subsequent atrophy, a process that can be inhibited by the promotion of autophagy. A direct comparison of local and systemic administration of mature recombinant IL-18 with current anti-VEGF (vascular endothelial growth factor)-based therapeutic strategies shows that IL-18 treatment works effectively alone and more effectively in combination with anti-VEGF therapy and represents a novel therapeutic strategy for the treatment of wet AMD.
Details
- Title: Subtitle
- IL-18 Attenuates Experimental Choroidal Neovascularization as a Potential Therapy for Wet Age-Related Macular Degeneration
- Creators
- Sarah L. Doyle - National Children’s Research CentreEma Ozaki - Trinity College DublinKiva Brennan - Trinity College DublinMarian M. Humphries - Trinity College DublinKelly Mulfaul - Trinity College DublinJames Keaney - Trinity College DublinPaul F. Kenna - Trinity College DublinArvydas Maminishkis - National Institutes of HealthAnna-Sophia Kiang - Trinity College DublinSean P. Saunders - Trinity College DublinEmily Hams - Trinity College DublinEd C. Lavelle - Trinity College DublinClair Gardiner - Trinity College DublinPadraic G. Fallon - Trinity College DublinPeter Adamson - GlaxoSmithKline (United Kingdom)Peter Humphries - Trinity College DublinMatthew Campbell - Trinity College Dublin
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.6(230), pp.230ra44-230ra44
- DOI
- 10.1126/scitranslmed.3007616
- PMID
- 24695684
- PMCID
- PMC12016488
- NLM abbreviation
- Sci Transl Med
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 11
- Grant note
- GSK; GlaxoSmithKline BrightFocus Foundation Health Research Board of Ireland; Health Research Board - Ireland 12/YI/B2614 / Science Foundation Ireland (SFI) European Research Council; European Research Council (ERC) SFI; Science Foundation Ireland (SFI) Enterprise Ireland Irish Research Council for Science Engineering and Technology; Irish Research Council for Science, Engineering and Technology; CGIAR United States Department of Defense (Telemedicine and Advanced Technology Research Center); United States Department of Defense
- Language
- English
- Date published
- 04/02/2014
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984771654002771
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