Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes
Open Access
- 17 February 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Diabetologia
- Vol. 53 (5), 971-979
- https://doi.org/10.1007/s00125-009-1655-6
Abstract
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. 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. 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. 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.This publication has 47 references indexed in Scilit:
- Retinal ganglion cells in diabetesJournal Of Physiology-London, 2008
- Roles of STAT3/SOCS3 Pathway in Regulating the Visual Function and Ubiquitin-Proteasome-dependent Degradation of Rhodopsin during Retinal InflammationOnline Journal of Public Health Informatics, 2008
- Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic RetinaDiabetes, 2008
- Neuroprotective Effects of Angiotensin II Type 1 Receptor (AT1R) Blocker, Telmisartan, via Modulating AT1R and AT2R Signaling in Retinal InflammationInvestigative Ophthalmology & Visual Science, 2006
- Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic RetinopathyJapanese Journal of Ophthalmology, 2006
- The Ins2AkitaMouse as a Model of Early Retinal Complications in DiabetesInvestigative Ophthalmology & Visual Science, 2005
- Death of Retinal Neurons in Streptozotocin-Induced Diabetic MiceInvestigative Ophthalmology & Visual Science, 2004
- Origins of the electroretinogram oscillatory potentials in the rabbit retinaVisual Neuroscience, 2004
- Activity-Dependent Transfer of Brain-Derived Neurotrophic Factor to Postsynaptic NeuronsScience, 2001
- Quantitative Assessment of the Synaptophysin Immuno-Reactivity of the Cortical Neuropil in Various Neurodegenerative Disorderswith DementiaDementia and Geriatric Cognitive Disorders, 1993