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.
