CHOLESTEROL ACCUMULATION IN HUMAN CORNEA - EVIDENCE THAT EXTRACELLULAR CHOLESTERYL ESTER-RICH LIPID PARTICLES DEPOSIT INDEPENDENTLY OF FOAMCELLS

The cornea is a connective tissue site where lipid accumulates as a pe ripheral arcus lipoides. We found that cholesterol, in predominantly e sterified form, progressively accumulated with age in the peripheral c orneas of 20- to 90-yr-old individuals. Ultrastructural studies showed extracellular solid spherical lipid particles (<200 nm in diameter) e nmeshed between collagen fibers. Immunostaining showed significant apo E and apoA-I, but very little apoB in the peripheral cornea. Lipid par ticles were extracted from minced corneas into a buffer and subjected to isopycnic density gradient centrifugation. The lipid particles had a density <1.02 g/ml, contained >75% of their cholesterol in esterifie d form, and were distributed in two populations with average diameters of 22 +/- 5 nm (SD) and 79 +/- 26 nm. Gel-filtration chromatographic analysis of the corneal lipid particles showed that most cholesterol e luted with the larger particles and these larger particles lacked apoB . ApoA-I was associated with lipid particles the size of HDL. Most apo E was associated with lipid particles larger than the apoA-I-containin g lipid particles and smaller than the large lipid particles that carr ied most of the corneal cholesterol. jlr Thus, the cholesteryl ester-r ich lipid particles that accumulate in the cornea are 1) similar to li pid particles previously localized within and isolated from human athe rosclerotic lesions, 2) accumulate without foam cells, and 3) may be d erived from low density lipoproteins that have lost their apoB and fus ed.