PMID- 29280053 OWN - NLM STAT- MEDLINE DCOM- 20180827 LR - 20191126 IS - 1559-1166 (Electronic) IS - 0895-8696 (Linking) VI - 64 IP - 2 DP - 2018 Feb TI - CD200Fc Attenuates Retinal Glial Responses and RGCs Apoptosis After Optic Nerve Crush by Modulating CD200/CD200R1 Interaction. PG - 200-210 LID - 10.1007/s12031-017-1020-z [doi] AB - To explore the hypothesis that CD200Fc, a CD200R1 agonist with anti-inflammatory properties, will inhibit retinal glial cells hyperactivation and retinal ganglion cells (RGCs) apoptosis after optic nerve injury. CD200Fc was immediately administered after optic nerve crush (ONC) once by intravitreal injection. Rats were euthanized at 5 days after ONC. The density of RGCs was counted by immunostaining of retina flat mounts for Brn3a. TUNEL assay, immunoblotting analysis of ionized calcium-binding adapter molecule 1(iba1) (microglia marker) and glial fibrillary acidic protein (GFAP) (astrocytes and Muller cells marker), RT-PCR analysis of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-8 and IL-10, ELISA measure protein levels of inflammatory cytokines and western blot analysis of CD200 and CD200R1 were evaluated. CD200Fc treatment suppressed ONC-induced RGCs loss through inhibition of RGCs apoptosis. Additionally, expression of glial cells activation markers GFAP and iba1 and production of pro-inflammatory cytokines (COX-2, iNOS, MCP-1, TNF-alpha, IL-8) were decreased in CD200Fc treated animals after ONC. Meanwhile, anti-inflammatory cytokine IL-10 was increased by CD200Fc treatment in ONC-induced rat retina. Finally, we found that CD200Fc significantly inhibited ONC-induced increased in expression of CD200 and raised the already high basal CD200R1 expression in the rat retina after ONC. Our results demonstrated that the anti-inflammatory effects of CD200Fc in ONC rats model through inhibited the activation of retinal glial cells via the interaction between CD200 and CD200R1, and the neuroprotective effects of CD200Fc on RGCs thought inhibited its apoptosis. FAU - Huang, Rong AU - Huang R AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. AD - Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, People's Republic of China. FAU - Lan, Qianqian AU - Lan Q AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Chen, Lifei AU - Chen L AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Zhong, Haibin AU - Zhong H AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Cui, Ling AU - Cui L AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Jiang, Li AU - Jiang L AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Huang, Hui AU - Huang H AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Li, Li AU - Li L AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Zeng, Siming AU - Zeng S AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. FAU - Li, Min AU - Li M AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. eyeminli@163.com. FAU - Zhao, Xin AU - Zhao X AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. eyexinz@163.com. FAU - Xu, Fan AU - Xu F AUID- ORCID: 0000-0002-7464-2749 AD - Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China. eyefanxu@163.com. LA - eng GR - 81660168/National Natural Science Foundation of China/ GR - 81560166/National Natural Science Foundation of China/ GR - 81460087/National Natural Science Foundation of China/ GR - 81760172/National Natural Science Foundation of China/ GR - 81760178/National Natural Science Foundation of China/ GR - 81660161/National Natural Science Foundation of China (CN)/ GR - No. 2012GXNSFAA276039/Natural Science Foundation of Guangxi Zhuang Autonomous Region/ GR - No. 2011GXNSFA018228/Natural Science Foundation of Guangxi Zhuang Autonomous Region/ PT - Journal Article DEP - 20171226 PL - United States TA - J Mol Neurosci JT - Journal of molecular neuroscience : MN JID - 9002991 RN - 0 (Antigens, CD) RN - 0 (Ccl2 protein, rat) RN - 0 (Cd200 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-8) RN - 0 (RGS Proteins) RN - 0 (Receptors, Immunologic) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - UQ4V77A8VA (antigens, CD200) SB - IM MH - Animals MH - Antigens, CD/administration & dosage/pharmacology/*therapeutic use MH - *Apoptosis MH - Chemokine CCL2/metabolism MH - Cyclooxygenase 2/metabolism MH - Interleukin-8/metabolism MH - Intravitreal Injections MH - Male MH - Neuroglia/*drug effects/metabolism MH - Nitric Oxide Synthase Type II/metabolism MH - Optic Nerve Injuries/*drug therapy MH - Protein Binding MH - RGS Proteins/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Immunologic/agonists/*metabolism MH - Retina/cytology/drug effects/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - CD200/CD200R interaction OT - CD200Fc OT - Inflammatory responses OT - Optic nerve crush OT - Retinal ganglion cells OT - Retinal glial cells EDAT- 2017/12/28 06:00 MHDA- 2018/08/28 06:00 CRDT- 2017/12/28 06:00 PHST- 2017/10/12 00:00 [received] PHST- 2017/12/15 00:00 [accepted] PHST- 2017/12/28 06:00 [pubmed] PHST- 2018/08/28 06:00 [medline] PHST- 2017/12/28 06:00 [entrez] AID - 10.1007/s12031-017-1020-z [pii] AID - 10.1007/s12031-017-1020-z [doi] PST - ppublish SO - J Mol Neurosci. 2018 Feb;64(2):200-210. doi: 10.1007/s12031-017-1020-z. Epub 2017 Dec 26.