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

• Published in: BMC ophthalmology Vol. 16; no. 1; p. 75
• Main Authors: Bae, Hyoung Won, Lee, Naeun, Seong, Gong Je, Rho, Seungsoo, Hong, Samin, Kim, Chan Yun
• Format: Journal Article
• Language: English
• Published: England BioMed Central 04.06.2016
• Subjects: Animals; Blotting, Western; Disease Models, Animal; Etanercept - therapeutic use; Humans; Immunohistochemistry; Ischemia - drug therapy; Ischemia - etiology; Male; Neuroprotective Agents - therapeutic use; Ophthalmology; Optic Nerve Diseases - drug therapy; Optic Nerve Diseases - etiology; Optic Nerve Diseases - pathology; Rats; Rats, Sprague-Dawley; Retinal Diseases - drug therapy; Retinal Diseases - pathology; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - pathology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor necrosis factor-α; Etanercept; Axonal injury; Acute ischemia; Microglia
• ISSN: 1471-2415; 1471-2415
• DOI: 10.1186/s12886-016-0262-9

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. 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. 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. 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.