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 peroxida tion, which leads to the formation of lipid peroxides. The lipid perox ides 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 pres ent studies was thus to investigate the role of HNE in hyperglycemic c ataract and understand the mechanism(s) of its prevention by antioxida nts and aldose reductase inhibitors. HNE and hyperglycemic cataract we re developed by culturing rat lenses in TC-199 medium containing 50 mu M HNE and 50 mM glucose, respectively. The effect of an antioxidant, trolox, and an aldose reductase inhibitor, sorbinil, on the progressio n of HNE and hyperglycemic cataract, evaluated by digital image analys is, was followed for 8 and 9 days, respectively. In lenses cultured wi th BNE, the decrease in transmitted Light was 43, 65, and 87% on Days 3, 5, and 8, respectively. Trolox ameliorated the HNE cataract, wherea s sorbinil accelerated the progression of IINE cataract and prevented the progression of hyperglycemic cataract. It is concluded that HNE fo rmed under hyperglycemia may play a pivotal role in diabetic cataracto genesis. (C) 1996 Academic Press, Inc.