Physiological Effects of Superoxide Dismutase on Altered Visual Function of Retinal Ganglion Cells in db/db Mice
Open Access
- 17 January 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (1), e30343
- https://doi.org/10.1371/journal.pone.0030343
Abstract
The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice. In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ON- and OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina. The altered visual functions of RGCs were characterized by the reduced RF center size, elevated LT, and attenuated contrast gain in 12 and 20 wk db/db mice, respectively. These altered visual functions could, at least partly, be due to oxidative stress since in vitro application of SOD effectively improves visual functions.Keywords
This publication has 54 references indexed in Scilit:
- Dietary wolfberry ameliorates retinal structure abnormalities in db/db mice at the early stage of diabetesExperimental Biology and Medicine, 2011
- Superoxide is an associated signal for apoptosis in axonal injuryBrain, 2010
- Inhibition of Reactive Oxygen Species by Lovastatin Downregulates Vascular Endothelial Growth Factor Expression and Ameliorates Blood-Retinal Barrier Breakdown in db/db MiceDiabetes, 2010
- Visual Response Properties of Y Cells in the Detached Feline RetinaInvestigative Ophthalmology & Visual Science, 2010
- Peroxynitrite Mediates Diabetes-Induced Endothelial Dysfunction: Possible Role of Rho Kinase ActivationExperimental Diabetes Research, 2010
- Retinal ganglion cells in diabetesThe Journal of Physiology, 2008
- Rod Photoreceptor Dysfunction in Diabetes: Activation, Deactivation, and Dark AdaptationInvestigative Ophthalmology & Visual Science, 2006
- Death of Retinal Neurons in Streptozotocin-Induced Diabetic MiceInvestigative Ophthalmology & Visual Science, 2004
- Large‐scale morphological survey of mouse retinal ganglion cellsJournal of Comparative Neurology, 2002
- Role of Oxidative Stress in Development of Complications in DiabetesDiabetes, 1991