Oxidative stress in the eye in diabetes

Abstract

AbstractPurpose The characterize manifestations of oxidative stress in lens and retina in diabetes, and to evaluate the roles for aldose reductase (AR), Na+‐H+‐exchanger‐1 (NHE‐1), and poly(ADP‐ribose) polymerase‐1 (PARP‐1) in oxidative stress in both tissues, cataract formation, and retinal apoptosis.Methods The experiments were performed in streptozotocin‐diabetic rats and high glucose‐exposed cultured human lens epithelial cells (HLEC) and bovine retinal pericytes and endothelial cells (BRP and BREC). Cataract formation was evaluated by indirect ophthalmoscopy and slit lamp examination, oxidative stress by combination of biochemical and immunohistochemical methods, and retinal apoptosis by TUNEL assay in flat‐mounted retinae.Results Diabetes‐induced oxidative‐nitrosative stress manifested by accumulation of free lipid peroxidation products, malondialdehyde and 4‐hydroxyalkenals, as well as 4‐hydroxynonenal protein adducts, and nitrated and poly(ADP‐ribosyl)ated proteins, is present in both diabetic lens and retina as well as in high glucose‐exposed HLEC and BRP and BREC. Depletion of GSH and ascorbate and changes in the glutathione and ascorbate redox states are present in thre lens only. Activation of AR, NHE‐1 and PARP‐1 promotes oxidative damage. Inhibition of AR, NHE‐1, and PARP‐1 prevents diabetes‐induced oxidative stress, and prevents or delays cataractogenesis and retinal apoptosis.Conclusion Ozidative stress is present in lens and retina in diabetes and plays an important role in diabetic ocular comp‐lications. Commercial interest