lewis-x-antigen and Cataract

We previously reported that human lens accumulates gangliosides in association with aging and senile cataract progression. Structural analysis revealed that gangliosides in human cataractous lenses were composed of ganglio-series gangliosides, such as GM3, GM2, GM1 and GD1a, and sialyl-Lewisx-containing neolacto-series gangliosides. Although Lewisx-containing neolacto-series glycolipid was found to accumulate in association with aging and cataract progression, the sialyl-Lewisx gangliosides did not show much accumulation in individual lenses from subjects between 16 and 80 years old. The content of sialyl-Lewisx gangliosides was about two to four times higher than that of Lewisx glycolipids, suggesting the possibility that the increase in Le(x) glycolipid is partly due to the desialylation of sialyl-Le(x) gangliosides. On the other hand, the expression of ganglio-series gangliosides increased in an age-related manner. Thus, age-related changes in lens glycolipids may modify the cell-to-cell interaction induced by cell surface sugar chains, leading to the initiation and progression of cataract.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Animals; Cataract; Chromatography, Thin Layer; Gangliosides; Glycosphingolipids; Humans; Lens, Crystalline; Lewis X Antigen; Macaca; Middle Aged; Oligosaccharides; Sialyl Lewis X Antigen

We have studied the glycolipid composition of human cataractous lenses. Neutral and acidic lipid fractions were isolated by column chromatographies on DEAE-Sephadex and Iatrobeads. The neutral glycolipid fraction and acidic glycolipid fraction contained 0.6-0.9 micrograms of lipid-bound glucose (Glc) per mg of protein and 0.8-1.3 micrograms of lipid-bound sialic acid (NeuAc) per mg of protein, respectively. The neutral glycolipid fraction was found to contain LacCer (39.0% of total neutral glycolipids), Gb3 (16.2%), Gb4 (1.1%), nLc4 (5.0%), X (29.0%), and Y (9.2%). The acidic lipid fraction was found to contain mainly GM3 (33.1% of the total ganglioside fraction), GM1 (8.3%), LM1 (7.3%), GD1a (16.0%), and G (30.1%). The structures of neutral glycolipids X and Y and ganglioside G were elucidated by high performance thin-layer chromatography overlay method of glycolipids, gas-liquid chromatography, proton NMR spectrometry, and liquid secondary ion mass spectrometry as follows: 1) X, Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer, III3FucnLc4 (Lex); 2) Y, Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1- 3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer, V3FucIII3FucnLc6; and 3) G, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3 Gal-beta 1-4Glc beta 1-1'Cer, IV3NeuAcIII3FucnLc4 (sialosyl-Le(x)). A minor neutral glycolipid Z was isolated and tentatively characterized as GlcNAc beta 1-3?Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer (GlcNAc-Le(x)), suggesting that it may be the precursor of glycolipid Y. The major long-chain base of these human cataract glycolipids was C18:0 sphingosine (sphinganine). The major fatty acids were C16:0, C24:1 and C24:0, and monounsaturated fatty acids accounted for 40-55% of the total fatty acids.

Topics: Aged; Carbohydrate Conformation; Carbohydrate Sequence; Carbohydrates; Cataract; Chromatography, Thin Layer; Fatty Acids; Gangliosides; Gas Chromatography-Mass Spectrometry; Glycolipids; Humans; Lens, Crystalline; Lewis X Antigen; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Oligosaccharides

A glycosphingolipid that reacted positively to anti-stage-specific embryonic antigen-1 (SSEA-1) antiserum accumulated in human lens in association with aging and senile cataract formation. Since this antiserum recognizes Lewis(x) (Le(x)) structure, Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, which is a typical tumor-associated and differentiation-related saccharide chain, the lens glycolipid was predicted to be a Lex antigen. The glycolipid purified from cataractous lens tissues was indeed a Lex glycolipid, Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1- 4Glc beta 1-1 ceramide. Enhanced expression of the Lex glycolipid may affect the organization of lens plasma membranes through Le(x)-Le(x) interactions, as suggested for compaction in mouse preimplantation embryos and embryonic teratocarcinomas, resulting in lens opacification, namely cataract.

Topics: Cataract; Chromatography, Thin Layer; Gangliosides; Glycolipids; Humans; Lens, Crystalline; Lewis X Antigen