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

 Hyoung Won Bae  ;  Naeun Lee  ;  Gong Je Seong  ;  Seungsoo Rho  ;  Samin Hong  ;  Chan Yun Kim 
 BMC OPHTHALMOLOGY, Vol.16 : 75, 2016 
Journal Title
Issue Date
Animals ; Blotting, Western ; Disease Models, Animal ; Etanercept/therapeutic use* ; Humans ; Immunohistochemistry ; Ischemia/drug therapy* ; Ischemia/etiology ; Male ; Neuroprotective Agents/therapeutic use* ; 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
Acute ischemia ; Axonal injury ; Etanercept ; Microglia ; Tumor necrosis factor-α
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.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chan Yun(김찬윤) ORCID logo https://orcid.org/0000-0002-8373-9999
Bae, Hyoung Won(배형원) ORCID logo https://orcid.org/0000-0002-8421-5636
Seong, Gong Je(성공제) ORCID logo https://orcid.org/0000-0002-5456-4296
Hong, Sa Min(홍사민)
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