Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy
Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy
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DOI：
10.1194/jlr.m400428-jlr200
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发表时间：
2005-04-01
影响因子：
6.5
通讯作者：
Curcio, CA
中科院分区：
文献类型：
--
作者：
Li, CM;Presley, B;Curcio, CA
年龄相关性黄斑病变（ARM）是老年人视力丧失的主要原因，其主要细胞外病变涉及Bruch膜（BrM），这是视网膜色素上皮（RPE）与其血液供应之间的薄血管内膜。随着年龄的增长，含有酯化胆固醇（EC）的80-100 nm固体颗粒在正常BrM中积累，在BrM和arm相关病变中可检测到载脂蛋白B （apoB）的免疫反应性。然而，几乎没有证据表明血浆胆固醇升高是ARM的危险因素。为了确定RPE是否能够组装其自身含载脂蛋白，我们检测了RPE中微粒体甘油三酯转移蛋白（MTP）的表达，这是该过程所必需的。与先前apoB表达的证据一致，MTP在RPE， ARPE-19细胞系中表达，出乎意料的是，在视网膜神经节细胞中表达，这是中枢神经系统的神经元。在补充油酸后，培养基中高水平的放射性标记EC和甘油三酯支持ARPE-19重新合成和分泌中性脂。脂蛋白的组装和分泌被认为是视网膜功能的组成部分，也是ARM细胞外含胆固醇病变形成的一个可能的候选机制。由MTP基因突变引起的色素视网膜病变和高蛋白血症神经病变（孟德尔遗传；basen - kornzwieg病）可能涉及视网膜功能丧失。
The principal extracellular lesions of age-related maculopathy (ARM), the leading cause of vision loss in the elderly, involve Bruch's membrane (BrM), a thin vascular intima between the retinal pigment epithelium (RPE) and its blood supply. With age, 80-100 nm solid particles containing esterified cholesterol (EC) accumulate in normal BrM, and apolipoprotein B (apoB) immunoreactivity is detectable in BrM- and ARM-associated lesions. Yet little evidence indicates that increased plasma cholesterol is a risk factor for ARM. To determine if RPE is capable of assembling its own apoB-containing lipoprotein, we examined RPE for the expression of microsomal triglyceride transfer protein (MTP), which is required for this process. Consistent with previous evidence for apoB expression, MTP is expressed in RPE, the ARPE-19 cell line, and, unexpectedly, retinal ganglion cells, which are neurons of the central nervous system. De novo synthesis and secretion of neutral lipid by ARPE-19 was supported by high levels of radiolabeled EC and triglyceride in medium after supplementation with oleate. Lipoprotein assembly and secretion is implicated as a constitutive retinal function and a plausible candidate mechanism involved in forming extracellular cholesterol-containing lesions in ARM. The pigmentary retinopathy and neuropathy of abetalipoproteinemia (Mendelian Inheritance of Man 200100; Bassen-Kornzwieg disease), which is caused by mutations in the MTP gene, may involve loss of function at the retina.