Pathogenesis of experimental lipid keratopathy. An ultrastructural study of an animal model system.
The histology and ultrastructure of experimental lipid keratopathy were studied in hypercholesterolemic rabbits in which the insertion of corneal sutures induced vascularization and subsequent lipid deposition in the anterior stroma. Lipid accumulated in the keratocytes, the pericytes and occasionally in the endothelial cells of the capillaries. The lipid-laden keratocytes were concentrated in the region of the capillaries. No lipid was seen in the control rabbits. In the hypercholesterolemic rabbit with sutures, intracellular lipid in the keratocytes was present largely in nonmembrane-limited droplets with smaller amounts of membrane-limited cholesterol crystals and rare numbers of myelin figures. In addition, large, lipid-engorged spherical cells were present. The numerous phagolysosomes seen ultrastructurally suggest that some of these cells probably represent macrophages. Keratocytes and the large, spherical lipid-engorged cells show focal degenerative changes, including pyknotic nuclei, cytoplasmic coagulation and membrane loss, leaving extracellular mixed accumulations of lipid and cytoplasmic organelles. Small numbers of lymphocytes and plasmacytoid cells were present. No corneal lipid was seen in animals with normocholesterolemia, with or without sutures. In hypercholesterolemic animals, a few lipid-laden keratocytes without macrophages were identified even in the absence of vessels. These morphologic studies support the hypothesis that the accumulation of the corneal lipid in this animal model of lipid keratopathy is the result of increased lysosomal uptake of lipid, probably as low density lipoprotein, from the extracellular space by the keratocytes. The rate of metabolism of this lipid is insufficient to clear the cells of the lipid and the subsequent lipid inspissation results in keratocyte death, leading to macrophage accumulation of lipid and free lipid in the stroma.
Roth
S I
SI
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
Stock
E L
EL
Siel
J M
JM
Mendelsohn
A
A
Reddy
C
C
Preskill
D G
DG
Ghosh
S
S
D000818:Animals; D003315:Cornea / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003316:Corneal Diseases / Q000209:etiology* / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D050356:Lipid Metabolism; D008854:Microscopy, Electron; D011817:Rabbits