Kliffen M, Lutgens E, Daemen M J, de Muinck E D, Mooy C M, de Jong P T
Department of Pathology, Erasmus University, Rotterdam, Netherlands.
Br J Ophthalmol. 2000 Dec;84(12):1415-9. doi: 10.1136/bjo.84.12.1415.
To investigate the APO(*)E3-Leiden mouse as an animal model for age related maculopathy (ARM) related extracellular deposits.
Eyes were obtained from APO(*)E3-Leiden transgenic mice on a high fat/cholesterol (HFC) diet (n=12) or on a normal mouse chow (n=6), for 9 months. As controls, eyes were collected from APO-E knockout mice on the same diets. From each mouse one eye was processed for microscopic evaluation and immunohistochemistry with a polyclonal antibody directed against human apo-E. Electron microscopy was also performed.
All 12 eyes of the APO()E3-Leiden mice on an HFC diet contained basal laminar deposit (BLD; class 1 to class 3), whereas two of six APO()E3-Leiden mice on normal chow showed BLD class 1. The ultrastructural aspects of this BLD were comparable with those seen in early BLD in humans, and BLD showed immunoreaction with anti-human-apo-E antibodies. No BLD was found in any of the control mice. Drusen were not detected in any of the mice.
These results indicate that APO(*)E3-Leiden mice can be used as animal model for the pathogenesis of BLD, and that a HFC diet enhances the accumulation of this deposit. Furthermore, this study supports the previously suggested involvement of dysfunctional apo-E in the accumulation of extracellular deposits in ARM.
研究载脂蛋白E3 - 莱顿小鼠作为与年龄相关性黄斑病变（ARM）相关细胞外沉积物的动物模型。
从高脂/高胆固醇（HFC）饮食的载脂蛋白E3 - 莱顿转基因小鼠（n = 12）或正常小鼠饲料喂养的载脂蛋白E3 - 莱顿转基因小鼠（n = 6）获取眼睛，喂养9个月。作为对照，从相同饮食的载脂蛋白E基因敲除小鼠收集眼睛。从每只小鼠取一只眼睛进行显微镜评估和用针对人载脂蛋白E的多克隆抗体进行免疫组织化学检测。还进行了电子显微镜检查。
HFC饮食的载脂蛋白E3 - 莱顿小鼠的所有12只眼睛均含有基底膜沉积物（BLD；1级至3级），而正常饲料喂养的6只载脂蛋白E3 - 莱顿小鼠中有2只显示1级BLD。这种BLD的超微结构方面与人类早期BLD所见相似，并且BLD与抗人载脂蛋白E抗体显示免疫反应。在任何对照小鼠中均未发现BLD。在任何小鼠中均未检测到玻璃膜疣。
这些结果表明，载脂蛋白E3 - 莱顿小鼠可作为BLD发病机制的动物模型，并且HFC饮食会增强这种沉积物的积累。此外，本研究支持先前提出的功能失调的载脂蛋白E参与ARM中细胞外沉积物积累的观点。
