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AAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice
Tuo, Jingsheng1; Pang, Ji-Jing2; Cao, Xiaoguang1,3; Shen, Defen1; Zhang, Jun1; Scaria, Abraham4; Wadsworth, Samuel C.4; Pechan, Peter4; Boye, Sanford L.2; Hauswirth, William W.2; Chan, Chi-Chao1
关键词Soluble Vegf Receptor-1 Age-related Macular Degeneration Animal Model Ccl2 Cx3cr1 Adeno-associated Virus Gene Therapy Retina
刊名NEUROBIOLOGY OF AGING
2012-02-01
DOI10.1016/j.neurobiolaging.2011.01.009
33期:2
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Geriatrics & Gerontology ; Neurosciences
研究领域[WOS]Geriatrics & Gerontology ; Neurosciences & Neurology
关键词[WOS]ENDOTHELIAL GROWTH-FACTOR ; LEBER CONGENITAL AMAUROSIS ; MACULAR DEGENERATION ; ADENOASSOCIATED VIRUS ; PIGMENT EPITHELIUM ; DEFICIENT MICE ; NITRIC-OXIDE ; MOUSE MODEL ; FACTOR VEGF ; RAT MODEL
英文摘要

To test the effects of adeno-associated virus encoding sFLT01 (AAV5.sFLT01) on the retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice, a model for age-related macular degeneration (AMD), AAV5.sFLT01 was injected into the subretinal space of the right eyes and the left eyes served as controls. Histology found no retinal toxicity due to the treatment after 3 months. The treated eyes showed lesion arrest compared with lesion progression in the left eyes by fundus monitoring monthly and histological evaluation 3 months after treatment. Retinal ultrastructure showed fewer lipofuscin and better preserved photoreceptors after the treatment. A2E, a major component of lipofuscin, was lower in the treated eyes than in the control eyes. Molecular analysis showed that AAV5.sFLT01 lowered retinal extracellular signal-regulated kinase (ERK) phosphorylation and inducible nitric oxide synthetase expression, which suggested the involvement of reactive nitrogen species in the retinal lesions of Ccl2(-/-)/Cx3cr1(-/-). We concluded that local delivery of AAV5.sFLT01 can stabilize retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice. The findings provide further support for the potential beneficial effects of sFLT01 gene therapy for age-related macular degeneration. Published by Elsevier Inc.

语种英语
WOS记录号WOS:000298171800053
资助机构National Eye Institute, National Institutes of Health
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文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58110
专题北京大学第二临床医学院_眼科
作者单位1.NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA
2.Univ Florida, Dept Ophthalmol, Gainesville, FL USA
3.Beijing Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100871, Peoples R China
4.Genzyme Corp, Dept Mol Biol, Framingham, MA 01701 USA
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Tuo, Jingsheng,Pang, Ji-Jing,Cao, Xiaoguang,et al. AAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice[J]. NEUROBIOLOGY OF AGING,2012,33(2).
APA Tuo, Jingsheng.,Pang, Ji-Jing.,Cao, Xiaoguang.,Shen, Defen.,Zhang, Jun.,...&Chan, Chi-Chao.(2012).AAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice.NEUROBIOLOGY OF AGING,33(2).
MLA Tuo, Jingsheng,et al."AAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice".NEUROBIOLOGY OF AGING 33.2(2012).
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