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学科主题临床医学
Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1rd8 background
Zhang, Jun1; Tuo, Jingsheng2; Cao, Xiaoguan2,3; Shen, Defen2; Li, Wei4; Chan, Chi-Chao1,2
关键词age-related macular degeneration cone synapse degeneration rod synapse plasticity animal model
刊名SYNAPSE
2013-08-01
DOI10.1002/syn.21674
67期:8页:515-531
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]AGE-RELATED MACULOPATHY ; ROD BIPOLAR CELLS ; EXPERIMENTAL RETINAL-DETACHMENT ; MACULAR DEGENERATION ; CONE PHOTORECEPTOR ; MOUSE MODEL ; RETINITIS-PIGMENTOSA ; MAMMALIAN RETINA ; CHEMOKINE RECEPTORS ; ELECTRON-MICROSCOPY
英文摘要

Photoreceptor ribbon synapse releases glutamate to postsynaptic targets. The synaptic ribbon may play multiple roles in ribbon synapse development, synaptic vesicle recycling, and synaptic transmission. Age-related macular degeneration (AMD) patients appear to have fewer or no detectable synaptic ribbons as well as abnormal swelling in the photoreceptor terminals in the macula. However, reports on changes of photoreceptor synapses in AMD are scarce and photoreceptor type and quantity affected in early AMD is still unclear. Here, we employed multiple anatomical techniques to investigate these questions in Ccl2-/-/Cx3cr1-/- mouse on Crb1rd8 background (DKO rd8) at one month of age. We found that approximately 17% of photoreceptors over the focal lesion were lost. Immunostaining for synapse-associated proteins (CtBP2, synaptophysin, and vesicular glutamate transporter 1) showed significantly reduced expression and ectopic localization. Cone opsins demonstrated dramatic reduction in expression (S-opsins) and extensive mislocalization (M-opsins). Quantitative ultrastructural analysis confirmed a significant decrease in the number of cone terminals and nuclei, numerous vacuoles in remaining cone terminals, reduction in the number of synaptic ribbons in photoreceptor terminals, and ectopic rod ribbon synapses. In addition, glutamate receptor immunoreactivity on aberrant sprouting of rod bipolar cells and horizontal cells were identified at the ectopic synapses. These results indicate that synaptic alterations occur at the early stages of disease and cones are likely more susceptible to damage caused by DKO rd8 mutation. They provide a new insight into potential mechanism of vision function lost due to synaptic degeneration before cell death in the early stages of AMD. Synapse 67:515-531, 2013. (c) 2013 Wiley Periodicals, Inc.

语种英语
WOS记录号WOS:000320777800006
资助机构National Eye Institute, NIH
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64024
专题北京大学第二临床医学院_眼科
作者单位1.NEI, Histol Core, NIH, Bethesda, MD 20892 USA
2.NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA
3.Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China
4.NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA
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Zhang, Jun,Tuo, Jingsheng,Cao, Xiaoguan,et al. Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1rd8 background[J]. SYNAPSE,2013,67(8):515-531.
APA Zhang, Jun,Tuo, Jingsheng,Cao, Xiaoguan,Shen, Defen,Li, Wei,&Chan, Chi-Chao.(2013).Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1rd8 background.SYNAPSE,67(8),515-531.
MLA Zhang, Jun,et al."Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1rd8 background".SYNAPSE 67.8(2013):515-531.
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