Accumulation of HDL apolipoproteins accompanies abnormal cholesterol accumulation in Schnyder's corneal dystrophy
Accumulation of HDL apolipoproteins accompanies abnormal cholesterol accumulation in Schnyder's corneal dystrophy
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DOI：
10.1161/01.atv.16.8.992
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发表时间：
1996-08-01
影响因子：
8.7
通讯作者：
Kruth, HS
中科院分区：
文献类型：
--
作者：
Gaynor, PM;Zhang, WY;Kruth, HS
Schnyder角膜营养不良是一种常染色体显性遗传疾病，其导致角膜中央混浊和角膜中外周弓的过早发育。以往的研究表明，脂质异常积聚是角膜混浊的基础。我们研究了载脂蛋白是否参与了这种疾病，并描述了施奈德营养不良患者角膜中央部分的脂质积聚。我们的研究结果表明，与正常角膜相比，受影响的角膜中胆固醇和磷脂含量分别增加了10倍和5倍以上。此外，与正常角膜相比，受影响的未酯化胆固醇的百分比（63%对50%）和未酯化胆固醇与磷脂的摩尔比（1.5对0.5）更高。大的多层囊泡和电子致密颗粒（直径100至300 nm）以及胆固醇晶体积聚在受影响角膜的细胞外基质中。免疫组织化学分析显示，HDL的载脂蛋白成分（apoA-I，apoA-II和apoE），但不是apoB，LDL的标志物，在受影响的角膜中积累。蛋白质印迹分析证实了受影响角膜中这些HDL载脂蛋白的量增加，并显示载脂蛋白的表观分子量正常。我们的研究结果首次表明，高密度脂蛋白载脂蛋白积累在患者的角膜与施奈德角膜营养不良。因此，这种疾病影响这些患者角膜中HDL的代谢。
Schnyder's corneal dystrophy is an autosomal dominant disorder that results in clouding of the central cornea and premature development of peripheral arcus in the cornea. Previous studies showed that abnormal lipid accumulation is the basis for the corneal clouding. We examined whether apolipoproteins are involved in this disorder and characterized the lipid accumulation in the central portion of corneas removed from patients with Schnyder's dystrophy. Our findings show that cholesterol and phospholipid contents increased greater than 10-fold and 5-fold, respectively, in affected compared with normal corneas. In addition, the percentage of cholesterol that was unesterified (63% versus 50%) and the molar ratio of unesterified cholesterol to phospholipid (1.5 versus 0.5) were higher in affected compared with normal corneas. Large multilamellar vesicles and electron-dense granules (100 to 300 nm in diameter) as well as cholesterol crystals accumulated in the extracellular matrix of affected corneas. Immunohistochemical analysis showed that apolipoprotein constituents of HDL (apoA-I, apoA-II, and apoE), but not apoB, a marker of LDL, accumulated in the affected cornea. Western blot analysis confirmed the increased amounts of these HDL apolipoproteins in affected corneas and showed that the apparent molecular weights of the apolipoproteins were normal. Our findings show for the first time that HDL apolipoproteins accumulate in the corneas of patients with Schnyder's corneal dystrophy. Thus, this disorder influences the metabolism of HDL in the corneas of these patients.