Molecular mechanism of cataractogenesis: III. Toxic metabolites of oxygen as initiators of lipid peroxidation and cataract

Abstract

A free radical mechanism of cataractogenesis involving enzymatic and nonenzymatic reactions, is proposed. Supporting experimental evidence is briefly reviewed. H2O2, which is one of the toxic metabolites of oxygen, was significantly increased 2-3 fold in ocular humors in several experimental cataracts and in human senile cataract. Various cataractogenic agents were also found to increase H2O2 in ocular humors in vivo prior to cataract formation. Enzymatic defenses against O2-. and H2O2 provided by superoxide dismutase, catalase and glutathione peroxidase were impaired in cataracts. In some cataracts, catalase and superoxide dismutase were affected earlier. Malondialdehyde (MDA), a major breakdown product of lipid peroxides was significantly increased by 2-4-fold in human senile cataract, in cataracts induced in rabbit and rat, and in hereditary cataracts in mice. All the reactive species of O2 (O2-., H2O2, OH. and 1 delta gO2) may participate in initiating lipid peroxidation of lens in vitro. Various scavengers of these species were capable of preventing lenticular lipid peroxidation, amongst which OH. scavengers were found to be the most effective. Biological antioxidant, vitamin E afforded 44% prevention of lipid peroxidation in lens. The important observation was that vitamin E was therapeutically effective in about 50% of animals in arresting cataract induced in rabbit by 3-aminotriazole. In these rabbits, H2O2 and ascorbic acid of ocular humors and MDA of lens were close to normal. It is our working hypothesis that the carbonyl groups of MDA and amino groups of amino acids, proteins, nucleic acids and their bases, and phospholipids could interact in a cross-linking reaction producing high molecular weight aggregates by Schiff-base conjugate formation in addition to disulfide cross-linking of proteins, and finally resulting in cataract.

Influence Dietary Riboflavin Deficiency on Lenticular Glutathione Redox Cycle, Lipid Peroxidation, and Free Radical Scavengers in the Rat

“…However, the lens contains a series of protective mechanism against these deleterious oxidants . These include enzymatic ones: SOIL, catalase, GSH-Px, and GSH-R as well as non-enzymatic: GSH, ascorbic acid and tocopherol [5,6,25].In the present study, GSH-R, which reduces GSSG to GSH and mediates the release of GSH from protein-GSH mixed disulfides [26] was decreased markedly in riboflavin deficiency. This finding conforms with our earlier observation [9] and with those of many others [7,8].…”

Lipids and the ocular lens

“…Malondialdehyde is a major secondary product of lipid oxidation. The concentration of malondialdehyde in the human lens increases with age ( 33 ) and cataract (5,33,(46)(47)(48)(49)(50)(51)(52). The association between lens opacity and lipid oxidation was so convincing that Babizhayev et al ( 50 ) boldly proclaimed that lipid oxidation may be an initiating step in the pathogenesis of human cataract.…”

Perfil socioeconômico e epidemiológico dos pacientes submetidos à cirurgia de catarata em um hospital universitário

“…Dois mecanismos principais parecem agir na sua patogênese: estresse foto-oxidativo (da radiação UVA e UVB) (1) e estresse oxidativo (drogas lícitas e ilícitas, diabetes, tabagismo, alcoolismo) (2) . O fator de risco isolado mais expressivo é a idade avançada, pelo maior tempo de exposição a todos esses fatores (3)(4) .A catarata é a principal causa mundial de cegueira, sendo responsável por 50% dos casos de incapacidade visual (5) .…”