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Peter Heiduschka, Lisa Pohlmann, Daniel Niekämper, Nicole Eter; Treatment of mature neovascularisation by targeting interleukin-8. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4420.
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As there can be a limited treatment success by anti-VEGF drugs in patients with neovascular diseases, e.g. if neovascularisation is maturated, we are looking for other factors that could play a role in CNV in the experimental model of laser-induced CNV in mice. We found a strong immunoreactivity for interleukin-8 (IL-8) after laser treatment, and we checked whether treatment with an anti-IL-8 antibody has an effect in the laser-induced CNV model.
Eyes of C57BL/6J mice were treated with an argon laser to induce CNV. Two weeks after laser treatment, antibodies against the following factors were injected intravitreally in groups 1 to 7: PBS as a control, VEGF, IL-8, VEGF+IL-8, PDGF-beta, PDGF-beta+IL-8, PDGF-beta+VEGF (n=8 for each group). Size of CNV was evaluated in vivo by scanning laser ophthalmoscopy (SLO) and fluorescein angiography (FA) two weeks after laser treatment, i.e. before intravitreal injections, and two weeks later. Afterwards, laser spots were labelled with isolectin B4 in choroidal flat mounts. We evaluated the changes of laser spot sizes as obtained by in vivo imaging by SLO (proliferation area) and FA (fluorescein leakage) expressed as ratio between the values before intravitreal injection and two weeks afterwards. Laser spot sizes in choroidal flat mounts were determined in mm2. Statistical analysis was performed by the one-way ANOVA test with Tukey correction.
For groups 1 to 7, mean ratios of changes of the proliferation area were 1.23, 1.05, 0.95, 0.88, 1.16, 0.85 and 1.69, mean ratios of changes of fluorescein leakage sizes were 0.97, 0.81, 0.81, 0.82, 2.10, 1.44 and 0.51, and mean laser spot sizes in choroidal flat mounts were 0.029, 0.019, 0.018, 0.014, 0.024, 0.016 and 0.020 mm2, respectively. CNV parameters were smaller when anti-VEGF or anti-IL-8 were injected alone, combined or together with anti-PDGF-beta, reaching statistical significance for the values of proliferation area and laser spot size in choroidal flat mounts after injection of anti-VEGF + anti-IL-8. No effects were observed when anti-PDGF was injected alone.
The results clearly indicate that sizes of mature laser spots in the experimental model of laser-induced CNV are reduced after intravitreal injection of an anti-IL-8 antibody alone or in combination with anti-VEGF or anti-PDGF-beta antibodies, thus possibly opening a new way to deal with treatment-resistive neovascularisations.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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