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学科主题: 临床医学
题名:
Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1rd8 background
作者: 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
发表日期: 2013-08-01
DOI: 10.1002/syn.21674
卷: 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
项目资助者: National Eye Institute, NIH
WOS记录号: WOS:000320777800006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64024
Appears in Collections:北京大学第二临床医学院_眼科_期刊论文

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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

Recommended Citation:
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.
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