ACCUMULATION OF HDL APOLIPOPROTEINS ACCOMPANIES ABNORMAL CHOLESTEROL ACCUMULATION IN SCHNYDERS CORNEAL-DYSTROPHY

Schnyder's corneal dystrophy is an autosomal dominant disorder that re sults in clouding of the central cornea and premature development of p eripheral arcus in the cornea. Previous studies showed that abnormal l ipid accumulation is the basis for the corneal clouding. We examined w hether apolipoproteins are involved in this disorder and characterized the lipid accumulation in the central portion of corneas removed from patients with Schnyder's dystrophy. Our findings show that cholestero l and phospholipid contents increased greater than 10-fold and 5-fold, respectively, in affected compared with normal corneas. In addition, the percentage of cholesterol that was unesterified (63% versus 50%) a nd the molar ratio of unesterified cholesterol to phospholipid (1.5 ve rsus 0.5) were higher in affected compared with normal corneas. Large multilamellar vesicles and electron-dense granules (100 to 300 nm in d iameter) as well as cholesterol crystals accumulated in the extracellu lar matrix of affected corneas. Immunohistochemical analysis showed th at apolipoprotein constituents of HDL (apoA-I, apoA-II, and apoE), but not apoB, a marker of LDL, accumulated in the affected cornea. Wester n blot analysis confirmed the increased amounts of these HDL apolipopr oteins in affected corneas and showed that the apparent molecular weig hts of the apolipoproteins were normal. Our findings show for the firs t time that HDL apolipoproteins accumulate in the corneas of patients with Schnyder's corneal dystrophy. Thus, this disorder influences the metabolism of HDL in the corneas of these patients.