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学科主题临床医学
Nutrient Supplementation with n3 Polyunsaturated Fatty Acids, Lutein, and Zeaxanthin Decrease A2E Accumulation and VEGF Expression in the Retinas of Ccl2/Cx3cr1-Deficient Mice on Crb1(rd8) Background
Ramkumar, Hema L.1,4,5; Tuo, Jingsheng1; Shen, De F.1; Zhang, Jun2; Cao, Xiaoguang1,6; Chew, Emily Y.3; Chan, Chi-Chao1,2
刊名JOURNAL OF NUTRITION
2013-07-01
DOI10.3945/jn.112.169649
143期:7页:1129-1135
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Nutrition & Dietetics
研究领域[WOS]Nutrition & Dietetics
关键词[WOS]ENDOTHELIAL GROWTH-FACTOR ; MACULAR DEGENERATION ; NITRIC-OXIDE ; EYE DISEASE ; PHOTORECEPTOR DEGENERATION ; MURINE MODEL ; VITAMIN-C ; CAROTENOIDS ; LIPOFUSCIN ; LESIONS
英文摘要

The Age-Related Eye Diseases Study 2 (AREDS2) clinical trial is assessing the effects of higher dietary xanthophyll (lutein and zeaxanthin) and long-chain n3 polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake on progression to advanced age-related macular degeneration (AMD). This study′s purpose was to examine the retinal effects of the AREDS2 formulation on Chemokine (C-C motif) ligand 2 (Ccl2(-/-))/CX3C chemokine receptor 1 (Cx3cr1(-/-)) mice on Crumbs homolog 1 retinal degeneration phenotype 8 (Crb1(rd8)) background (DKO), which develop focal retinal lesions with certain features similar to AMD. DKO and C57BL/6N rd8 background mice (WT) were bred and randomized into 4 groups. Two groups, WT mice on AREDS2 diet (A-WT) and DKO mice on AREDS2 diet (A-DKO), were supplemented daily with 1.76 mu mol of lutein, 35.1 mu mol of zeaxanthin, 215 mu mol EPA, and 107 mu mol of DHA, and 2 control groups, WT mice on control diet (C-WT) and DKO mice on control diet (C-DKO), were fed an isocaloric diet. All mice had monthly fundus photos and were killed after 3 mo for biochemical and histologic analyses. After 3 mo, 81% of A-DKO mice had lesion regression compared with 25% of C-DKO mice (P < 0.05). Toxic retinal 2-[2,6-dimethyl-8(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium (A2E) concentrations were significantly lower in A-DKO compared with C-DKO mice. The outer nuclear layer thickness in A-DKO mice was significantly greater than that in C-DKO mice. Retinal expression of inducible nitric oxide synthase (iNos) tumor necrosis factor-alpha (Tnf-alpha), Cyclooxygenase-2 (Cox-2), interleukin1beta (IL-1 beta), and vascular endothelial growth factor (Vegf) was significantly lower in A-DKO compared with C-DKO mice. Xanthophylls and LCPUFAs have antiinflammatory, neuroprotective, and antiangiogenic properties. Our data provide potential mechanisms by which the AREDS2 formula has a protective effect on retinal lesions in DKO mice.

语种英语
WOS记录号WOS:000320894800016
资助机构Intramural Research Program of the National Eye Institute ; NIH ; Howard Hughes Medical Institute
引用统计
被引频次:32[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/400002259/61900
专题北京大学第二临床医学院_眼科
作者单位1.NEI, NIH, Bethesda, MD 20892 USA
2.Howard Hughes Med Inst, Chevy Chase, MD USA
3.NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA
4.NEI, Histol Core, NIH, Bethesda, MD 20892 USA
5.Univ Calif San Diego, Dept Ophthalmol, Shiley Eye Ctr, San Diego, CA 92103 USA
6.Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China
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Ramkumar, Hema L.,Tuo, Jingsheng,Shen, De F.,et al. Nutrient Supplementation with n3 Polyunsaturated Fatty Acids, Lutein, and Zeaxanthin Decrease A2E Accumulation and VEGF Expression in the Retinas of Ccl2/Cx3cr1-Deficient Mice on Crb1(rd8) Background[J]. JOURNAL OF NUTRITION,2013,143(7):1129-1135.
APA Ramkumar, Hema L..,Tuo, Jingsheng.,Shen, De F..,Zhang, Jun.,Cao, Xiaoguang.,...&Chan, Chi-Chao.(2013).Nutrient Supplementation with n3 Polyunsaturated Fatty Acids, Lutein, and Zeaxanthin Decrease A2E Accumulation and VEGF Expression in the Retinas of Ccl2/Cx3cr1-Deficient Mice on Crb1(rd8) Background.JOURNAL OF NUTRITION,143(7),1129-1135.
MLA Ramkumar, Hema L.,et al."Nutrient Supplementation with n3 Polyunsaturated Fatty Acids, Lutein, and Zeaxanthin Decrease A2E Accumulation and VEGF Expression in the Retinas of Ccl2/Cx3cr1-Deficient Mice on Crb1(rd8) Background".JOURNAL OF NUTRITION 143.7(2013):1129-1135.
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