RT Journal Article SR Electronic T1 IL-18 Attenuates Experimental Choroidal Neovascularization as a Potential Therapy for Wet Age-Related Macular Degeneration JF Science Translational Medicine FD American Association for the Advancement of Science SP 230ra44 OP 230ra44 DO 10.1126/scitranslmed.3007616 VO 6 IS 230 A1 Doyle, Sarah L. A1 Ozaki, Ema A1 Brennan, Kiva A1 Humphries, Marian M. A1 Mulfaul, Kelly A1 Keaney, James A1 Kenna, Paul F. A1 Maminishkis, Arvydas A1 Kiang, Anna-Sophia A1 Saunders, Sean P. A1 Hams, Emily A1 Lavelle, Ed C. A1 Gardiner, Clair A1 Fallon, Padraic G. A1 Adamson, Peter A1 Humphries, Peter A1 Campbell, Matthew YR 2014 UL http://stm.sciencemag.org/content/6/230/230ra44.abstract AB 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-1β 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.