Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin.
Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin.
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DOI：
10.1016/j.freeradbiomed.2011.11.021
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发表时间：
2012-02-01
影响因子：
7.4
通讯作者：
Finnemann, Silvia C.
中科院分区：
文献类型：
--
作者：
Yu, Chia-Chia;Nandrot, Emeline F.;Dun, Ying;Finnemann, Silvia C.
关键词：
在衰老的人眼中，氧化损伤和促氧化剂溶酶体脂褐素的积累导致视网膜色素上皮（RPE）的功能下降，这有助于年龄相关性黄斑变性。在由于缺乏αvβ5整联蛋白受体而导致RPE特异性吞噬缺陷的小鼠中，脂褐质的RPE蓄积表明我们先前在该模型中描述的年龄相关性失明也可能是由氧化应激引起的。眼睛中氧化应激的细胞和分子靶点仍然知之甚少。在这里，我们确定肌动蛋白4-羟基壬烯醛（HNE）加合物中形成的β5−/− RPE，而不是随着年龄的神经视网膜。HNE修饰与肌动蛋白对去污剂提取的抗性损失直接相关，表明老化RPE中的细胞骨架损伤。富含天然抗氧化剂葡萄或含有黄斑色素叶黄素/玉米黄质的金盏花提取物的膳食足以防止β5−/−小鼠中HNE加合物形成、肌动蛋白溶解度、脂褐质积累以及年龄相关的视锥和视杆细胞功能障碍。HNE加合物的急性产生直接使RPE细胞的肌动蛋白而不是微管蛋白细胞骨架元件不稳定。这些研究结果确定了肌动蛋白细胞骨架的不稳定性，作为RPE细胞在体内的生理，亚致死氧化负荷的结果，与年龄相关的失明，可以通过食用富含抗氧化剂的饮食来预防。
In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of αvβ5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in β5−/− RPE but not neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants grapes or marigold extract containing macular pigments lutein/zeaxanthin was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in β5−/− mice. Acute generation of HNE-adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet.
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影响因子：
4.4
作者：
Justilien, Verline;Pang, Ji-Jing;Lewin, Alfred S.
通讯作者：
Lewin, Alfred S.
DOI：
10.1084/jem.20041447
发表时间：
2004-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nandrot EF;Kim Y;Brodie SE;Huang X;Sheppard D;Finnemann SC
通讯作者：
Finnemann SC
影响因子：
4.4
作者：
Ethen, Cheryl M.;Reilly, Cavan;Ferrington, Deborah A.
通讯作者：
Ferrington, Deborah A.
影响因子：
4.4
作者：
Rózanowska, M;Pawlak, A;Simon, JD
通讯作者：
Simon, JD
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