Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL 35294-0009, USA.
Prog Retin Eye Res. 2009 Nov;28(6):393-422. doi: 10.1016/j.preteyeres.2009.08.001. Epub 2009 Aug 19.
The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch's membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE). It occurs in the same compartment as drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD. Here we present evidence from light microscopic histochemistry, ultrastructure, lipid profiling of tissues and isolated lipoproteins, and gene expression analysis that this deposition can be accounted for by esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles constitutively produced by the RPE. This work collectively allows ARMD lesion formation and its aftermath to be conceptualized as a response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (CAD) (Tabas et al., 2007). This approach provides a wide knowledge base and sophisticated clinical armamentarium that can be readily exploited for the development of new model systems and the future benefit of ARMD patients.
年龄相关性黄斑变性（AMD）的最大风险因素是年龄增长。人类视网膜的一个显著与年龄相关的变化是在整个成年期，正常的布鲁赫膜（BrM）中可检测到中性脂质的积累。这种变化有可能对视网膜色素上皮（RPE）的生理学产生重大影响。它发生在与 drusen 和基底线性沉积物相同的部位，后者是 AMD 的特征性细胞外含脂病变。在这里，我们从光镜组织化学、超微结构、组织和分离脂蛋白的脂质分析以及基因表达分析提供证据表明，这种沉积可以归因于 RPE 持续产生的富含酯化胆固醇和载脂蛋白 B 的脂蛋白颗粒。这项工作共同使 AMD 病变的形成及其后果可以被理解为对内皮下载脂蛋白 B 脂蛋白的保留的反应，类似于广泛接受的动脉粥样硬化性冠状动脉疾病（CAD）模型（Tabas 等人，2007）。这种方法提供了广泛的知识库和复杂的临床武器库，可以方便地用于开发新的模型系统，并为 AMD 患者的未来带来好处。
