Role of lipid aldehydes in cataractogenesis: 4-hydroxynonenal-induced cataract

Free radicals have extremely short half-lives and they readily oxidize lipids and initiate an autocatalytic chain reaction of lipid peroxidation, which leads to the formation of lipid peroxides. The lipid peroxides undergo degradation to form metastable lipid aldehydes such as 4-hydroxynonenal (HNE). We have shown earlier that under hyperglycemia, lipid peroxides increase; and aldose reductase, an enzyme that reduces glucose to sorbitol, efficiently reduces HNE. The purpose of the present studies was thus to investigate the role of HNE in hyperglycemic cataract and understand the mechanism(s) of its prevention by antioxidants and aldose reductase inhibitors. HNE and hyperglycemic cataract were developed by culturing rat lenses in TC-199 medium containing 50 microM HNE and 50 mM glucose, respectively. The effect of an anti-oxidant, trolox, and an aldose reductase inhibitor, sorbinil, on the progression of HNE and hyperglycemic cataract, evaluated by digital image analysis, was followed for 8 and 9 days, respectively. In lenses cultured with HNE, the decrease in transmitted light was 43, 65, and 87% on Days 3, 5, and 8, respectively. Trolox ameliorated the HNE cataract, whereas sorbinil accelerated the progression of HNE cataract and prevented the progression of hyperglycemic cataract. It is concluded that HNE formed under hyperglycemia may play a pivotal role in diabetic cataractogenesis.