PURPOSE: To examine the effectiveness of interleukin-18 (IL-18) on choroidal neovascularization (CNV) and retinal pigment epithelium (RPE) in humans and mice. METHODS: Serum IL-18 levels in patients with wet and dry AMD who were older than 50 years were measured and compared with those of age-matched controls. In mice, laser photocoagulation was performed in the retina to induce experimental CNV, and CNV volume was measured in eyes injected with recombinant IL-18 (rIL-18) and IL-18 neutralizing antibody (nIL-18Ab) compared with those injected with control. Tube formation assay was performed on human retinal endothelial cells (HREC) with rIL-18 administration in vitro. After subretinal injection of rIL-18, fundus change in the injected eyes was evaluated; active caspase-3 level was measured in the RPE/choroid complex, and tight junction integrity in RPE was visualized by zonula occludens-1 (ZO-1) staining. RESULTS: Serum IL-18 levels in dry AMD patients were higher than those in control. Mouse rIL-18 or nIL-18Ab did not induce significant change in CNV volume compared with controls or change tube formation in HREC. Subretinal injection of rIL-18 induced retinal degeneration in the mice fundus; ZO-1 staining showed considerably disturbed RPE structure, and active caspase-3 expression was significantly higher after rIL-18 induction. CONCLUSIONS: Interleukin-18 did not show a pro- or antiangiogenic effect on mouse laser-induced CNVs (laser-CNVs), whereas it directly induced RPE cell apoptosis in the mouse eye. Our results suggested that IL-18 is associated with dry AMD, but not with wet AMD. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: To examine the effectiveness of interleukin-18 (IL-18) on choroidal neovascularization (CNV) and retinal pigment epithelium (RPE) in humans and mice. METHODS: Serum IL-18 levels in patients with wet and dry AMD who were older than 50 years were measured and compared with those of age-matched controls. In mice, laser photocoagulation was performed in the retina to induce experimental CNV, and CNV volume was measured in eyes injected with recombinant IL-18 (rIL-18) and IL-18 neutralizing antibody (nIL-18Ab) compared with those injected with control. Tube formation assay was performed on human retinal endothelial cells (HREC) with rIL-18 administration in vitro. After subretinal injection of rIL-18, fundus change in the injected eyes was evaluated; active caspase-3 level was measured in the RPE/choroid complex, and tight junction integrity in RPE was visualized by zonula occludens-1 (ZO-1) staining. RESULTS: Serum IL-18 levels in dry AMDpatients were higher than those in control. MouserIL-18 or nIL-18Ab did not induce significant change in CNV volume compared with controls or change tube formation in HREC. Subretinal injection of rIL-18 induced retinal degeneration in the mice fundus; ZO-1 staining showed considerably disturbed RPE structure, and active caspase-3 expression was significantly higher after rIL-18 induction. CONCLUSIONS:Interleukin-18 did not show a pro- or antiangiogenic effect on mouse laser-induced CNVs (laser-CNVs), whereas it directly induced RPE cell apoptosis in the mouse eye. Our results suggested that IL-18 is associated with dry AMD, but not with wet AMD. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Luping Wang; Sarah Schmidt; Petra P Larsen; Johanna H Meyer; William R Roush; Eicke Latz; Frank G Holz; Tim U Krohne Journal: J Mol Med (Berl) Date: 2019-02-10 Impact factor: 4.599
Authors: Younghee Kim; Valeria Tarallo; Nagaraj Kerur; Tetsuhiro Yasuma; Bradley D Gelfand; Ana Bastos-Carvalho; Yoshio Hirano; Reo Yasuma; Takeshi Mizutani; Benjamin J Fowler; Shengjian Li; Hiroki Kaneko; Sasha Bogdanovich; Balamurali K Ambati; David R Hinton; William W Hauswirth; Razqallah Hakem; Charles Wright; Jayakrishna Ambati Journal: Proc Natl Acad Sci U S A Date: 2014-10-27 Impact factor: 11.205