Age-related retinopathy in NRF2-deficient mice.
Age-related retinopathy in NRF2-deficient mice.
复制标题
DOI：
10.1371/journal.pone.0019456
复制
发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Cai J
中科院分区：
文献类型：
--
作者：
Zhao Z;Chen Y;Wang J;Sternberg P;Freeman ML;Grossniklaus HE;Cai J
累积性氧化损伤与年龄相关性黄斑变性（AMD）的发病机制有关。核因子红细胞2相关因子2（NRF 2）是一种转录因子，在视网膜抗氧化和解毒反应中起关键作用。本研究的目的是确定NRF 2缺陷小鼠是否会随着年龄的增长而发展出AMD样视网膜病变，并探索其潜在机制。通过眼底照相术和视网膜电图（ERG）在体内检查野生型和Nrf 2 −/−小鼠的眼睛。用光镜、电镜及免疫荧光标记技术观察了老年动物视网膜外层结构的变化。我们的研究结果表明，Nrf 2 −/−小鼠在视网膜色素上皮（RPE）中出现了年龄依赖性退行性病变。12个月后，Nrf 2 −/−小鼠中出现了Drusen样沉积物、脂褐素积累、自发性脉络膜新生血管（CNV）和炎症蛋白的RPE下沉积。自噬相关空泡和多泡体的积累通过电子显微镜在老年Nrf 2 −/−小鼠的RPE和Bruch膜中进行鉴定。我们的数据表明，Nfe 2l 2基因的破坏增加了外视网膜对年龄相关性变性的脆弱性。NRF 2缺陷型小鼠的眼部病理学与人类AMD的主要特征相似，失调的自噬可能是氧化损伤和炎症之间的机制联系。Nrf 2 −/−小鼠可以为AMD的机制和转化研究提供新的模型。
Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms. Eyes of both wild type and Nrf2−/− mice were examined in vivo by fundus photography and electroretinography (ERG). Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2−/− mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE). Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV) and sub-RPE deposition of inflammatory proteins were present in Nrf2−/− mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microcopy both within the RPE and in Bruch's membrane of aged Nrf2−/− mice. Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2−/− mice can provide a novel model for mechanistic and translational research on AMD.
登录
查看更多内容
影响因子：
4.4
作者：
Justilien, Verline;Pang, Ji-Jing;Lewin, Alfred S.
通讯作者：
Lewin, Alfred S.
影响因子：
4.8
作者：
Jain, Ashish;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
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
影响因子：
--
作者：
Albert, Daniel M.;Neekhra, Aneesh;Wang, Shoujian;Darjatmoko, Soesiawati R.;Sorenson, Christine M.;Dubielzig, Richard R.;Sheibani, Nader
通讯作者：
Sheibani, Nader
DOI：
10.1073/pnas.93.24.13943
发表时间：
1996-11-26
影响因子：
11.1
作者：
Chan, KM;Lu, RH;Kan, YW
通讯作者：
Kan, YW