Research ArticlesRetinal Disease

IL-18 Attenuates Experimental Choroidal Neovascularization as a Potential Therapy for Wet Age-Related Macular Degeneration

Science Translational Medicine  02 Apr 2014:
Vol. 6, Issue 230, pp. 230ra44
DOI: 10.1126/scitranslmed.3007616

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Treating Age-Related Macular Degeneration with IL-18

Age-related macular degeneration (AMD) comes in two forms: “wet” and “dry.” Dry AMD is characterized by the death of various eye cells, whereas wet AMD arises from the formation of new blood vessels in the choroid. The only treatment for AMD is antibodies against growth factors that regulate vascular growth; this is not a cure, but rather a chronic therapy requiring direct injection into the eye. Seeking out a new therapy, Doyle and colleagues found that an inflammatory cytokine, interleukin-18 (IL-18), works to prevent neovascularization in animal models. The eyes of mice were hit with a laser to induce blood vessel growth, or choroidal neovascularization (CNV), which mimics the human AMD pathology. Recombinant, mature IL-18 injected into the eyes of mice or subcutaneously limited CNV formation. It has been suggested that IL-18 is toxic, but Doyle et al. showed that this is not the case through in vitro and in vivo studies; the “pro” form of the cytokine is, however, and can be regulated by autophagy. Because IL-18 is being tested in patients with cancer, the authors believe that this could translate and readily complement existing antiangiogenic strategies currently used for AMD, such as the antibody-based therapies targeting vascular endothelial growth factor (VEGF).