Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes

M. Sasaki, Y. Ozawa, T. Kurihara, S. Kubota, K. Yuki, K. Noda, S. Kobayashi, S. Ishida, K. Tsubota

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Aims/hypothesis: Diabetic retinopathy is a progressive neurodegenerative disease, but the underlying mechanism is still obscure. Here, we focused on oxidative stress in the retina, and analysed its influence on retinal neurodegeneration, using an antioxidant, lutein. Methods: C57BL/6 mice with streptozotocin-induced diabetes were constantly fed either a lutein-supplemented diet or a control diet from the onset of diabetes, and their metabolic data were recorded. In 1-month-diabetic mice, reactive oxygen species (ROS) in the retina were measured using dihydroethidium and visual function was evaluated by electroretinograms. Levels of activated extracellular signal-regulated kinase (ERK), synaptophysin and brain-derived neurotrophic factor (BDNF) were also measured by immunoblotting in the retina of 1-month-diabetic mice. In the retinal sections of 4-month-diabetic mice, histological changes, cleaved caspase-3 and TUNEL staining were analysed. Results: Lutein did not affect the metabolic status of the diabetic mice, but it prevented ROS generation in the retina and the visual impairment induced by diabetes. ERK activation, the subsequent synaptophysin reduction, and the BDNF depletion in the diabetic retina were all prevented by lutein. Later, in 4-month-diabetic mice, a decrease in the thickness of the inner plexiform and nuclear layers, and ganglion cell number, together with increase in cleaved caspase-3- and TUNEL-positive cells, were avoided in the retina of lutein-fed mice. Conclusions/interpretation: The results indicated that local oxidative stress that has a neurodegenerative influence in the diabetic retina is prevented by constant intake of a lutein-supplemented diet. The antioxidant, lutein may be a potential therapeutic approach to protect visual function in diabetes.

Original languageEnglish
Pages (from-to)971-979
Number of pages9
JournalDiabetologia
Volume53
Issue number5
DOIs
Publication statusPublished - 2010 May

Keywords

  • Apoptosis
  • BDNF
  • Diabetes
  • ERK
  • Lutein
  • Oxidative stress
  • ROS
  • Retina
  • Synaptophysin
  • Visual function

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes'. Together they form a unique fingerprint.

  • Cite this