Protein oxidation and lens opacity in humans.

PURPOSE Oxidative damage to lens proteins is a major factor leading to cataract formation. It is of pathogenic importance to determine a threshold of protein oxidation over which opacification of the lens takes place. METHODS Sixty-two lenses extracted from patients affected by idiopathic senile, diabetic, or myopic cataract were studied. Clear lenses were obtained from subjects undergoing enucleation (n = 10) or vitrectomy for giant retinal tears (n = 9), and were age- and sex-matched to those with cataract. The content of carbonyls and sulfhydryls (P-SH) in proteins in the lens was assessed using spectrophotometric assay. RESULTS An age-associated inverse relation (P < 0.01) was noted in the content of P-SH, the concentrations of which were also inversely related (P < 0.03) to the content of protein carbonyls. These changes were more pronounced in cataracts than in clear lenses and in diabetic and myopic cataracts when compared with senile cataracts. The drop of P-SH concentration occurred earlier in diabetic and in myopic cataracts than in senile cataracts. The accumulation of protein carbonyls > 2 nmol/mg protein and the decrease of P-SH below 12 to 10 nmol/mg protein were always accompanied by lens opacification. CONCLUSIONS Idiopathic senile, diabetic, and myopic cataractogenesis appear to be dependent on oxidative damage to lens proteins. This damage occurs earlier in myopic and diabetic patients. Values of P-SH below and protein carbonyls above their specific threshold were found to be predictive for the presence of cataract. Because increased oxidation was observed in clear lenses removed from myopic and diabetic subjects, oxidation may be involved in the pathogenesis of these forms of human cataract.