Protective effect of etanercept, an inhibitor of tumor necrosis factor-α, in a rat model of retinal ischemia

Background: To assess the neuroprotective effect of etanercept (Enbrel®) which is a commercialized Tumor necrosis factor-α (TNF-α) inhibitor on axonal injury in an animal model of acute ischemia. Methods: Acute ischemia was induced by intraocular pressure elevation in 36 rats. The treatment groups underwent subcutaneous injection of etanercept (0.3 or 1.0 mg/kg) three times per week up to 4 weeks. The control groups were treated in the same manner using the same volume of phosphate-buffered saline (PBS). Optic nerve damage was evaluated by counting the number of axons under a transmission electron microscope. Microglial cell activity was assessed using Iba1 and CD68. Results: After induction of ischemia, the ratio of preserved axons was significantly greater in the 2-week 1.0-mg/kg etanercept-treated group than in the PBS-treated group (p = 0.062). The 4-week 0.3-mg/kg and 1.0-mg/kg etanercept-treated groups also showed significantly higher ratios of preserved axons than did the PBS-treated group (p = 0.021 and 0.003, respectively). The expression of Iba1 and CD68 in the optic nerve was lower in the etanercept-treated groups than in the PBS-treated groups. Immunohistochemical staining using rabbit anti-Iba1 antibody showed that the amount of microglia at the optic nerve head was noticeably lower in the etanercept-treated groups than in the PBS-treated groups. Conclusions: Etanercept significantly suppressed optic nerve injury in this rat model of acute ischemia. This in vivo study suggests that etanercept might be a novel neuroprotective treatment agent for TNF-α-related disease.