Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina

doi:10.1016/j.exer.2014.06.003

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina
	Guo, Xian Jun; Tian, Xue Song; Ruan, Zhi; Chen, Yu Ting; Wu, Lei; Gong, Qi; Wang, Wei; Zhang, Hai Yan
刊名	EXPERIMENTAL EYE RESEARCH
	2014-08
卷号	125 页码:156-163
关键词	bilateral common carotid arteries occlusion retina neurotrophic system inflammation extracellular signal-regulated kinase cAMP-responsive element binding protein
ISSN号	0014-4835
DOI	10.1016/j.exer.2014.06.003
文献子类	Article
英文摘要	Although permanent bilateral common carotid artery occlusion (2VO) has been demonstrated to induce retinal injury, there is still a lack of systematic research on the complex processing of retinal degeneration. In the present study, time-dependent (at three, 14, 60 days after 2VO surgery) changes of neurotrophic and inflammatory systems, as well as cAMP-responsive element binding protein (CREB) signaling, which has been previously reported to effectively regulate these two systems, were evaluated. First, a morphological study confirmed that 2VO surgery progressively induced severe inner retinal degeneration and down-regulation of synaptic proteins, PSD95 and synaptophysin. The mRNA or protein levels of neurotrophic factors (NGF, BDNF, NT-3 and GDNF) and their receptors (TrkA, TrkB and TrkC) showed marked and persistent down-regulation in the rat retina since three days after 2VO surgery, whereas the gene transcription levels of CNTF were increased and p75(NTR) mRNA levels remained unchanged. In contrast to inner retinal degeneration, retinal Muller cells displayed rapid and prolonged activation since three days after 2VO lesion, whereas the microglia cell number, and TNF-alpha and IL-1 beta levels showed a robust increase with a maximal effect at three days and returned to levels that were slightly over baseline at 14 and 60 days after 2VO lesion. Interestingly, the gene expression levels of iNOS significantly decreased in the rat retina at both three and 14 days after 2VO surgery. Finally, as we hypothesized, remarkable reduction of CREB and extracellular signal-regulated kinase (ERK) phosphorylation levels were observed in the rat retina at three days after 2VO surgery. Thus, for the first time, our study demonstrated that chronic ischemia induced long-term aberrant CREB signaling and time-dependent progressive dysregulation of neurotrophic and inflammatory systems in the retina, which may provide important clues for a better understanding of the pathogenesis of retinal ischemic damage. (C) 2014 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[81173034] ; National Natural Science Foundation of China[81072646] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2012ZX09301001-004] ; Ministry of Science and Technology of China[2011CB510004]
WOS关键词	CAROTID-ARTERY OCCLUSION ; ELEMENT-BINDING PROTEIN ; MULLER CELLS ; GANGLION-CELLS ; NITRIC-OXIDE ; DIABETIC-RETINOPATHY ; IN-VITRO ; EXPRESSION ; BRAIN ; DEGENERATION
WOS研究方向	Ophthalmology
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号	WOS:000340079300018
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276964]
专题	药理学第二研究室
通讯作者	Zhang, Hai Yan
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Guo, Xian Jun,Tian, Xue Song,Ruan, Zhi,et al. Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina[J]. EXPERIMENTAL EYE RESEARCH,2014,125:156-163.
APA	Guo, Xian Jun.,Tian, Xue Song.,Ruan, Zhi.,Chen, Yu Ting.,Wu, Lei.,...&Zhang, Hai Yan.(2014).Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina.EXPERIMENTAL EYE RESEARCH,125,156-163.
MLA	Guo, Xian Jun,et al."Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina".EXPERIMENTAL EYE RESEARCH 125(2014):156-163.