Age- and light-dependent development of localised retinal atrophy in CCL2(-/-)CX3CR1(GFP/GFP) mice.
Age- and light-dependent development of localised retinal atrophy in CCL2(-/-)CX3CR1(GFP/GFP) mice.
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DOI：
10.1371/journal.pone.0061381
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Chen M;Hombrebueno JR;Luo C;Penalva R;Zhao J;Colhoun L;Pandi SP;Forrester JV;Xu H
以前的研究表明，C57BL/6N背景(带有RD8突变)的CCL2/CX3CR1缺陷小鼠具有早期(6周)的自发性视网膜变性。在本研究中，我们在C57BL/6J背景下建立了CCL2−/−CX3CR1GFP/gfp小鼠。CCL2−/−CX3CR1GFP/gfp小鼠6月龄未见视网膜变性。12个月龄的17只∼和18个月龄的CCL2CX3CR1GFP/∼小鼠分别有60%、30%和100%的小鼠可见白色/淡黄色眼底斑块。荧光血管造影术显示，这些小鼠没有脉络膜新生血管。在12月龄和18月龄的CCL2CX3CR1GFP/−/−小鼠中，分别有30%和50%的小鼠视网膜色素上皮斑块和光感受器受损，而野生型小鼠则没有。所有CCL2−/−CX3CR1GFP/GFP小鼠在超强光照(∼800lux，6小时/天，6个月)下均出现视网膜斑块萎缩，而接受相同光照处理的WT小鼠中只有20%-25%出现萎缩病变。此外，在CCL2−/−CX3CR1GFP/gfp小鼠与光感受器丢失相关的区域外核层也检测到突触素的表达。CCL2、−/−、CX3CR1GFP/GFP老龄小鼠视网膜外层视紫红质表达显著增加，视锥芳香素表达降低。CCL2CX3CR1GFP/gfp老龄−/−小鼠视网膜内GABA表达降低。与年龄匹配的WT小鼠相比，CCL2CX3CR1GFP/gfp小鼠的Müler神经胶质细胞和小胶质细胞的激活显著增加。CCL2−/−CX3CR1GFP/gfp小鼠在低氧条件下巨噬细胞吞噬功能较弱，但表达较高水平的诱导型一氧化氮合酶、白介素1β、白介素12和肿瘤坏死因子α。我们的结果表明，CCL2和CX3CR1的缺失使小鼠容易受到年龄和光介导的视网膜损伤。CCL2/CX3CR1基因缺陷小鼠可作为老年性视网膜色素上皮萎缩性变性的模型，包括干性黄斑变性、地理性萎缩。
Previous studies have shown that CCL2/CX3CR1 deficient mice on C57BL/6N background (with rd8 mutation) have an early onset (6 weeks) of spontaneous retinal degeneration. In this study, we generated CCL2−/−CX3CR1GFP/GFP mice on the C57BL/6J background. Retinal degeneration was not detected in CCL2−/−CX3CR1GFP/GFP mice younger than 6 months. Patches of whitish/yellowish fundus lesions were observed in 17∼60% of 12-month, and 30∼100% of 18-month CCL2−/−CX3CR1GFP/GFP mice. Fluorescein angiography revealed no choroidal neovascularisation in these mice. Patches of retinal pigment epithelium (RPE) and photoreceptor damage were detected in 30% and 50% of 12- and 18-month CCL2−/−CX3CR1GFP/GFP mice respectively, but not in wild-type mice. All CCL2−/−CX3CR1GFP/GFP mice exposed to extra-light (∼800lux, 6 h/day, 6 months) developed patches of retinal atrophy, and only 20–25% of WT mice which underwent the same light treatment developed atrophic lesions. In addition, synaptophysin expression was detected in the outer nucler layer (ONL) of area related to photoreceptor loss in CCL2−/−CX3CR1GFP/GFP mice. Markedly increased rhodopsin but reduced cone arrestin expression was observed in retinal outer layers in aged CCL2−/−CX3CR1GFP/GFP mice. GABA expression was reduced in the inner retina of aged CCL2−/−CX3CR1GFP/GFP mice. Significantly increased Müller glial and microglial activation was observed in CCL2−/−CX3CR1GFP/GFP mice compared to age-matched WT mice. Macrophages from CCL2−/−CX3CR1GFP/GFP mice were less phagocytic, but expressed higher levels of iNOS, IL-1β, IL-12 and TNF-α under hypoxia conditions. Our results suggest that the deletions of CCL2 and CX3CR1 predispose mice to age- and light-mediated retinal damage. The CCL2/CX3CR1 deficient mouse may thus serve as a model for age-related atrophic degeneration of the RPE, including the dry type of macular degeneration, geographic atrophy.
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影响因子：
3.7
作者：
Luhmann UF;Lange CA;Robbie S;Munro PM;Cowing JA;Armer HE;Luong V;Carvalho LS;MacLaren RE;Fitzke FW;Bainbridge JW;Ali RR
通讯作者：
Ali RR
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
4.4
作者：
Chen, Mei;Luo, Chang;Xu, Heping
通讯作者：
Xu, Heping
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
DOI：
10.1073/pnas.222551899
发表时间：
2002-11-12
影响因子：
11.1
作者：
Crabb, JW;Miyagi, M;Hollyfield, JG
通讯作者：
Hollyfield, JG