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学科主题: 临床医学
题名:
AAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice
作者: 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
发表日期: 2012-02-01
DOI: 10.1016/j.neurobiolaging.2011.01.009
卷: 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
项目资助者: National Eye Institute, National Institutes of Health
WOS记录号: WOS:000298171800053
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58110
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, 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

Recommended Citation:
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).
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