Systemic Administration of IL-6 Receptor Antibody Suppresses Choroidal Neovascularization (CNV) in Mice

Abstract

Purpose:: It has previously been demonstrated that IL-6 is up-regulated by inducing CNV in the murine CNV tissues and IL-6-mediated angiogenesis is dependent on Vascular Endothelial Growth Factor (VEGF). Anti-mouse IL-6 receptor (IL-6R) antibody specifically binds to IL-6R and blocks IL-6 binding to IL-6R. This study sought to determine if systemic administration of IL-6R antibody could suppress CNV in the murine model.

Methods:: Adult C57BL/6 mice were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. The effect of subcutaneous injections of IL-6R antibody was tested in mice with laser-induced rupture of Bruch’s membrane at 3 locations in each eye. Mice received subcutaneous injections of 2mg of IL-6R antibody, or vehicle twice a week starting immediately after laser. Fourteen days after laser, mice were perfused with fluorescein-labeled dextran and the area of CNV at Bruch’s membrane rupture sites was measured on choroidal flat mounts by image analysis. For expression studies, mice were administrated IL-6R antibody or vehicle after laser. After 24 hours, mice were euthanized and eyes were dissected and homogenized followed by extraction of mRNA. RT-PCR was used to assess the effect of subcutaneous injection of IL-6R antibody on VEGF mRNA levels.

Results:: Compared to vehicle injections, subcutaneous injections of 2 mg of IL-6R antibody twice a week resulted in significant reductions in CNV area of 20%, (p<0.05). VEGF mRNA was decreased compared to vehicle injected mice.

Conclusions:: These data confirm that IL-6R antibody may provide a new agent for treatment of patients with CNV.

Keywords: choroid: neovascularization • neovascularization • drug toxicity/drug effects