期刊
NATURE MEDICINE
卷 14, 期 2, 页码 194-198出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm1709
关键词
-
资金
- NEI NIH HHS [K08 EY014912, R21EY017153, R24 EY015638-05, R01 EY014240, K08EY014912, R01EY014240, R56EY10240, R24 EY015638, R56 EY014240, R56 EY014240-06, R24EY015638, R21 EY017153, R01 EY014240-06] Funding Source: Medline
- NIGMS NIH HHS [R01GM21249, R01 GM021249] Funding Source: Medline
Oxidative damage and inflammation are postulated to be involved in age-related macular degeneration (AMD). However, the molecular signal(s) linking oxidation to inflammation in this late-onset disease is unknown. Here we describe AMD-like lesions in mice after immunization with mouse serum albumin adducted with carboxyethylpyrrole, a unique oxidation fragment of docosahexaenoic acid that has previously been found adducting proteins in drusen from AMD donor eye tissues(1) and in plasma samples(2) from individuals with AMD. Immunized mice develop antibodies to this hapten, fix complement component-3 in Bruch's membrane, accumulate drusen below the retinal pigment epithelium during aging, and develop lesions in the retinal pigment epithelium mimicking geographic atrophy, the blinding end-stage condition characteristic of the dry form of AMD. We hypothesize that these mice are sensitized to the generation of carboxyethylpyrrole adducts in the outer retina, where docosahexaenoic acid is abundant and conditions for oxidative damage are permissive. This new model provides a platform for dissecting the molecular pathology of oxidative damage in the outer retina and the immune response contributing to AMD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据