PMID- 27259948 OWN - NLM STAT- MEDLINE DCOM- 20170202 LR - 20181113 IS - 1471-2415 (Electronic) IS - 1471-2415 (Linking) VI - 16 DP - 2016 Jun 4 TI - Protective effect of etanercept, an inhibitor of tumor necrosis factor-alpha, in a rat model of retinal ischemia. PG - 75 LID - 10.1186/s12886-016-0262-9 [doi] LID - 75 AB - BACKGROUND: To assess the neuroprotective effect of etanercept (Enbrel(R)) which is a commercialized Tumor necrosis factor-alpha (TNF-alpha) 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-alpha-related disease. FAU - Bae, Hyoung Won AU - Bae HW AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea. FAU - Lee, Naeun AU - Lee N AD - Department of Ophthalmology, Hallym Hospital, Incheon, South Korea. FAU - Seong, Gong Je AU - Seong GJ AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea. FAU - Rho, Seungsoo AU - Rho S AD - Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea. FAU - Hong, Samin AU - Hong S AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea. FAU - Kim, Chan Yun AU - Kim CY AD - 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. LA - eng PT - Journal Article DEP - 20160604 PL - England TA - BMC Ophthalmol JT - BMC ophthalmology JID - 100967802 RN - 0 (Neuroprotective Agents) RN - 0 (Tumor Necrosis Factor-alpha) RN - OP401G7OJC (Etanercept) SB - IM MH - Animals MH - Blotting, Western MH - Disease Models, Animal MH - Etanercept/*therapeutic use MH - Humans MH - Immunohistochemistry MH - Ischemia/*drug therapy/etiology MH - Male MH - Neuroprotective Agents/*therapeutic use MH - Optic Nerve Diseases/*drug therapy/etiology/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Retinal Diseases/*drug therapy/pathology MH - Retinal Ganglion Cells/drug effects/pathology MH - Tumor Necrosis Factor-alpha/antagonists & inhibitors PMC - PMC4893298 OTO - NOTNLM OT - Acute ischemia OT - Axonal injury OT - Etanercept OT - Microglia OT - Tumor necrosis factor-alpha EDAT- 2016/06/05 06:00 MHDA- 2017/02/06 06:00 PMCR- 2016/06/04 CRDT- 2016/06/05 06:00 PHST- 2015/08/18 00:00 [received] PHST- 2016/05/28 00:00 [accepted] PHST- 2016/06/05 06:00 [entrez] PHST- 2016/06/05 06:00 [pubmed] PHST- 2017/02/06 06:00 [medline] PHST- 2016/06/04 00:00 [pmc-release] AID - 10.1186/s12886-016-0262-9 [pii] AID - 262 [pii] AID - 10.1186/s12886-016-0262-9 [doi] PST - epublish SO - BMC Ophthalmol. 2016 Jun 4;16:75. doi: 10.1186/s12886-016-0262-9.