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.