Role of glycation in modification of lens crystallins in diabetic and nondiabetic senile cataracts.
To assess the significance of glycation, nonenzymatic browning, and oxidation of lens crystallins in cataract formation in elderly diabetic patients, we measured three distinct products of glycation, browning, and oxidation reactions in cataractous lens crystallins from 29 diabetic patients (mean +/- SD age 72.8 +/- 8.8 yr) and 24 nondiabetic patients (age 73.5 +/- 8.3 yr). Compounds measured included 1) fructoselysine (FL), the first stable product of glycation; 2) pentosidine, a fluorescent, carbohydrate-derived protein cross-link between lysine and arginine residues formed during nonenzymatic browning; and 3) N epsilon-(carboxymethyl)lysine (CML), a product of autoxidation of sugar adducts to protein. In diabetic compared with nondiabetic patients, there were significant increases (P less than 0.001) in HbA1 (10.2 +/- 3.1 vs. 7.1 +/- 0.7%), FL (7.6 +/- 5.4 vs. 1.7 +/- 1.2 mmol/mol lysine), and pentosidine (6.3 +/- 2.8 vs. 3.8 +/- 1.9 mumol/mol lysine). The disproportionate elevation of FL compared with HbA1 suggests a breakdown in the lens barrier to glucose in diabetes, whereas the increase in pentosidine is indicative of accelerated nonenzymatic browning of diabetic lens crystallins. CML levels were similar in the two groups (7.1 +/- 2.4 vs. 6.8 +/- 3.0 mmol/mol lysine), providing no evidence for increased oxidative stress in the diabetic cataract. Thus, although the modification of lens crystallins by autoxidation reactions was not increased in diabetes, the increase in glycation and nonenzymatic browning suggests that these processes may acclerate the development of cataracts in diabetic patients.
Lyons
T J
TJ
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, Northern Ireland, United Kingdom.
Silvestri
G
G
Dunn
J A
JA
Dyer
D G
DG
Baynes
J W
JW
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis; D002386:Cataract / Q000378:metabolism*; D002387:Cataract Extraction; D003459:Crystallins / Q000032:analysis*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male
D003459:Crystallins; C033186:fructosyl-lysine; C048496:N(6)-carboxymethyllysine; D001120:Arginine; C062187:pentosidine; D008239:Lysine