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Comment
. 2014 Dec;20(12):1372-5.
doi: 10.1038/nm.3671.

IL-18 is not therapeutic for neovascular age-related macular degeneration

Yoshio Hirano  1 , Tetsuhiro Yasuma  1 , Takeshi Mizutani  2 , Benjamin J Fowler  1 , Valeria Tarallo  3 , Reo Yasuma  1 , Younghee Kim  1 , Ana Bastos-Carvalho  1 , Nagaraj Kerur  1 , Bradley D Gelfand  4 , Sasha Bogdanovich  1 , Shikun He  5 , Xiaohui Zhang  6 , Miho Nozaki  2 , Ryo Ijima  7 , Hiroki Kaneko  7 , Yuichiro Ogura  2 , Hiroko Terasaki  7 , Hiroshi Nagai  8 , Isao Haro  9 , Gabriel Núñez  10 , Balamurali K Ambati  11 , David R Hinton  5 , Jayakrishna Ambati  12
Affiliations
Comment

IL-18 is not therapeutic for neovascular age-related macular degeneration

Yoshio Hirano et al. Nat Med. 2014 Dec.
No abstract available

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Figures

Figure 1
Figure 1. IL18 administration does not affect choroidal angiogenesis
a–e. Recombinant IL18 (rIL18) (30 pg–1,000 ng) did not decrease CNV at one week after laser injury in wild-type mice, NS compared to PBS (Independent experiments from different laboratories, a: BA, n = 12; b: DH, n = 8; c: HT, n = 16; d: YO, n = 14; e: JA, n = 17). f. Meta-analysis of datasets presented in Fig. 1a–e, with error bars denoting 95% confidence interval. NS, not significant. All error bars indicate mean ± s.e.m, Mann Whitney U test. Data from laboratories of: BA (Balamurali Ambati), DH (David Hinton), HT (Hiroko Terasaki), YO (Yuichiro Ogura), JA (Jayakrishna Ambati). n = number of eyes per condition.
Figure 2
Figure 2. Glycerol, but not IL18 deficiency, increases choroidal angiogenesis
a–d. The pro-angiogenic effect of the anti-IL18 antibody ab71495 was due to glycerol in the diluent. a. Ab71495 (1 μg antibody which contains 8.57 μmol glycerol) increased CNV in wild type mice compared to isotype IgG (1 μg antibody; no glycerol). (DH, n = 8). b. Glycerol increased CNV in wild type mice (JA, n = 14–17). c. Ab71495 (1 μg), its diluent (Abcam diluent) alone, and isotype IgG (1 μg) constituted with Abcam diluent increased CNV in wild-type mice compared to sham injection or PBS, whereas isotype IgG (1 μg) in PBS diluent did not increase CNV (n = 11–21). d. Ab71495 (1 μg) or isotype IgG (1 μg) constituted with Abcam diluent, but not an isotype IgG in PBS, increased CNV in Il18−/− mice, compared to PBS injection (n = 6–12). e. Ab71495 (1 μg), its diluent (Abcam diluent) alone, and isotype IgG (1 μg) constituted with Abcam diluent did not increase CNV compared to PBS in mice deficient for aquaporin-1 (Aqp1−/−) (n = 16). f. Neither the neutralizing anti-IL18 antibody MBL D048-3 (30 ng which contains 0.128 μmol glycerol) nor an isotype IgG (30 ng) increased CNV compared to PBS in wild-type mice (n = 18–20). a–f, final glycerol concentration of injections shown in μmol. a–d *, P < 0.05, Mann Whitney U test. e,f NS, not significant. CNV volumes were measured at one week after laser injury. All error bars indicate mean ± s.e.m. DH, data from laboratory of David Hinton; unless specified, data from lab of JA (Jayakrishna Ambati). n = number of eyes per condition.
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References

    1. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP. Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol. 2003;48:257–293. - PubMed
    1. Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration. Nat Rev Immunol. 2013;13:438–451. - PMC - PubMed
    1. Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron. 2012;75:26–39. - PMC - PubMed
    1. Kaneko H, et al. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature. 2011;471:325–330. - PMC - PubMed
    1. Tarallo V, et al. DICER1 Loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88. Cell. 2012;149:847–859. - PMC - PubMed

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