Cholesterol accumulation in human cornea: evidence that extracellular cholesteryl ester-rich lipid particles deposit independently of foam cells

The cornea is a connective tissue site where lipid accumulates as a peripheral arcus lipoides. We found that cholesterol, in predominantly esterified form, progressively accumulated with age in the peripheral corneas of 20- to 90-yr-old individuals. Ultrastructural studies showed extracellular solid spherical lipid particles (< 200 nm in diameter) enmeshed between collagen fibers. Immunostaining showed significant apoE and apoA-I, but very little apoB in the peripheral cornea. Lipid particles 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 esterified 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 eluted with the larger particles and these larger particles lacked apoB. ApoA-I was associated with lipid particles the size of HDL. Most apoE was associated with lipid particles larger than the apoA-I-containing lipid particles and smaller than the large lipid particles that carried most of the corneal cholesterol. Thus, the cholesteryl ester-rich lipid particles that accumulate in the cornea are 1) similar to lipid particles previously localized within and isolated from human atherosclerotic lesions, 2) accumulate without foam cells, and 3) may be derived from low density lipoproteins that have lost their apoB and fused.