Intravenous immunoglobulin treatment inhibits choroidal and corneal neovascularization via FcyR1

Abstract

Purpose: The antibody bevacizumab is widely used to treat ocular neovascularization. Interestingly, bevacizumab has been shown to block mouse models of neovascularization, despite the fact that the Fab domain does not recognize mouse VEGF-A. Therefore, we hypothesized that antibodies can inhibit angiogenesis via their Fc domain. Intravenous immunoglobulin treatment (IVIG) is an Fc-containing, widely-used therapeutic used to treat many diseases. Here, we tested whether IVIG is anti-angiogenic via the Fc receptor FcyR1 in choroidal and corneal neovascularization.

Methods: To induce choroidal angiogenesis, laser photocoagulation was performed on both eyes using a 532-nm laser. Seven days after treatment, eyes were enucleated and CNV lesions were labeled with FITC-conjugated isolectin B4, and volumes determined using a confocal microscope. For the corneal angiogenesis model, 11-0 nylon sutures were placed into the corneal stroma between the corneal apex and the limbus. On day 10 after surgery, the mean percentage CD31⁺Lyve-1^- blood vessel areas on corneal flat mounts was calculated. IVIG was administrated by tail vein or intravitreous injection. Experiments were performed in wild-type and Fcgr1^-/- mice.

Results: Both systemic and intraocular IVIG inhibited angiogenesis in wild-type, but not Fcgr1^-/- mice, compared with PBS-injected control group, in both of choroidal and corneal neovascularization models.

Conclusions: Intravenous immunoglobulin treatment is a novel anti-angiogenic agent for ocular neovacularization that functions via an unexpected FcyR1-mediated mechanism.

Keywords: 412 age-related macular degeneration • 453 choroid: neovascularization • 555 immunomodulation/immunoregulation