Suppression of Choroidal Neovascularization by Blocking Interleukin–6 Receptor Signaling

Abstract

Purpose: : Interleukin (IL)–6 is suggested to be a risk factor for choroidal neovascularization (CNV) since its serum levels increased in patients with age–related macular degeneration (AMD). We investigate the role of IL–6 receptor signaling in the development of CNV using a murine model of CNV.

Methods: : Laser photocoagulation was performed to induce CNV in C57BL/6 mice. Choroidal protein and mRNA levels of IL–6 in laser–treated mice three days after photocoagulation were examined by RT–PCR and ELISA, respectively. A rat anti–mouse IL–6 receptor monoclonal antibody, MR16–1, was administered at the dose of 10 or 100 µg /g body weight (BW) immediately after the photocoagulation. One week after the photocoagulation, CNV volume was evaluated by volumetric measurements.

Results: : In mice with CNV, choroidal IL–6 mRNA and protein levels were significantly (P < 0.05) higher than in age–matched normal controls. CNV volume was significantly suppressed by the treatment with MR16–1 (400427 ± 95917 µm3 for 10 µg/g BW, 290256 ± 74982 µm3 for 100 µg/g BW), compared with vehicle–treated animals (496216± 81286 µm3).

Conclusions: : IL–6 receptor signaling blockade led to suppression of CNV development. These results suggest the possibility of IL–6 receptor blockade as a therapeutic strategy to suppress CNV associated with AMD.

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