CHOLESTEROL DEPOSITION IN HUMAN CORNEA

人角膜中的胆固醇沉积

• 批准号: 3858067
• 负责人: H S KRUTH
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858067
• 关键词: atherosclerotic plaque; autosomal dominant trait; cholesterol; cholesterol esters; cornea; cornea opacity; crystallization; fluorescent dye /probe; human tissue; phospholipids; scanning electron microscopy; stainings; vascular endothelium

Cholesterol accumulates pathologically not only in atherosclerotic vessels but also in the cornea. This project focuses on pathological deposition of cholesterol in corneal tissue as a means to more generally understand deposition and removal of cholesterol from all tissues. We characterized lipid accumulation in central corneas removed from probands of three kindreds with autosomal dominantly inherited corneal lipid deposition. Predominantly extracellular deposits of unesterified cholesterol in both crystalline and non-crystalline forms were observed in corneal tissue sections using histochemical staining of cholesterol with filipin and electron microscopy. Corneal tissue sections also contained lipid deposits which stained with oil red 0 suggesting the presence of cholesteryl ester accumulation. Thus, patient corneas accumulated greater than 10-fold total cholesterol and 5-fold phospholipid as compared to normal corneas. Patient and normal corneas contained equals approximately 50% of their total cholesterol in esterified form. The lipid accumulation that occurs in the corneas of these patients is remarkably similar both histochemically and chemically to that which occurs in human atherosclerotic lesions. In both diseases, unesterified and esterified cholesterol accumulate in the extracellular space and in cells. Thus, elucidation of the genetic factors responsible for cholesterol accumulation in this corneal dystrophy should be helpful in determining what local vessel wall factors may contribute to cholesterol deposition during development of atherosclerotic plaques.

胆固醇不仅在动脉粥样硬化中病理性积聚 血管也在角膜中。这个项目的重点是病理性的 角膜组织中胆固醇的沉积作为一种更普遍的手段 了解胆固醇在所有组织中的沉积和清除。我们 先证者取出的中央角膜中有特征性的脂类积聚 常染色体显性遗传角膜脂蛋白的三个家系 证词。主要是未酯化的胞外沉积物 观察到结晶和非结晶两种形式的胆固醇 在角膜组织切片中使用胆固醇组织化学染色 用菲力平和电子显微镜检查。角膜组织切片也 含有油红0染色的脂类沉淀物，表明 存在胆固醇酯蓄积。因此，患者的角膜 累积的总胆固醇超过10倍，是5倍 磷脂与正常角膜相比。患者和正常角膜 所含的胆固醇约占其总胆固醇的50% 酯化形式。角膜中发生的脂肪堆积 这些患者在组织化学和化学上都非常相似。 与在人类动脉粥样硬化病变中发生的情况相同。在这两种疾病中， 未酯化和酯化的胆固醇在细胞外积聚 空间和单元格。因此，对遗传因素的解释 对于这种角膜营养不良的胆固醇积聚应该是有帮助的 在确定局部血管壁因素可能对什么起作用 动脉粥样硬化斑块形成过程中的胆固醇沉积。