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.
Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea.
Hyoung Won
HW
Bae
Department of Ophthalmology, Hallym Hospital, Incheon, South Korea.
Naeun
N
Lee
Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea.
Gong Je
GJ
Seong
Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Seungsoo
S
Rho
Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea.
Samin
S
Hong
Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea. kcyeye@yuhs.ac.
Chan Yun
CY
Kim
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D000068800:Etanercept / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009901:Optic Nerve Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000188:drug therapy* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
Acute ischemia; Axonal injury; Etanercept; Microglia; Tumor necrosis factor-α