Retinal Nrf2 expression in normal and early streptozotocin-diabetic rats

Abstract

Diabetic retinopathy is the most common cause of vision loss among diabetic patients. Although hyperglycemia produces retinal oxidative stress in long-standing diabetes, the pathogenesis mechanism is unknown. The Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a central role in cell responses against oxidative damage. We used adult Long Evans rats where diabetes was induced by streptozotocin. Normal and treated rats were sacrificed at 7, 20, and 45 days after streptozotocin injection. We analyzed Nrf2 and Keap1 expression in retinal homogenates, cytoplasmic, and nuclear retinal fractions. Normal retina showed Nrf2 expression in all retina nuclear layers. We found a transitory decrease of Nrf2 mRNA and protein expression at 7 and 20 days after the streptozotocin injection that recovered later on: moreover, the protein level increased after 45 days. Keap1 immunoprecipitation revealed similar levels as Nrf2 in normal and diabetic rat retinas, indicating that the diabetic condition did not lead to dissociation of the Keap1-Nrf2 complex. Indeed, glutathione levels and superoxide dismutase activity were not altered in the treated rat retinas. These results do not support oxidative stress in the retina shortly after diabetes induction.