Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/83131
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Type: Journal article
Title: Mechanisms of neuroprotection by glucose in rat retinal cell cultures subjected to respiratory inhibition
Author: Han, G.
Wood, J.
Chidlow, G.
Mammone, T.
Casson, R.
Citation: Investigative Ophthalmology & Visual Science, 2013; 54(12):7567-7577
Publisher: Assoc Research Vision Ophthalmology Inc
Issue Date: 2013
ISSN: 0146-0404
1552-5783
Statement of
Responsibility: 
Guoge Han, John P. M. Wood, Glyn Chidlow, Teresa Mammone, and Robert J. Casson
Abstract: Purpose. Previous experiments have demonstrated that short-term hyperglycemia in rats renders the retina resistant to subsequent metabolic insults. The present study aimed to elucidate putative mechanisms involved in this protective response. Methods. Retinal cultures comprising neurons and glia were treated with the mitochondrial complex I inhibitor, rotenone, at a range of concentrations, for up to 24 hours. In some cases, glucose or the alternative energy substrates, pyruvate or lactate, and/or inhibitors of glycolysis or the pentose phosphate pathway (PPP) were also applied. Cell viability was assessed using complementary techniques: immunocytochemistry, immunoblotting, cytotoxicity assay, and TUNEL. Cellular levels of ATP, reactive oxygen species (ROS), and nicotinamide adenine dinucleotide phosphate (NAD[P]H) were also assessed. Results. Rotenone caused the preferential loss of neurons from retinal cultures in a concentration-dependent manner; glial cells were also affected, but only at a higher concentrations (10 μM). Cell loss was by apoptosis, and was preceded by a reduction of both cellular ATP and NAD(P)H levels and an increase in the production of ROS. Glucose counteracted the detrimental effects of rotenone. This involved a reduction in ROS levels and an increase in the cellular ATP/NAD(P)H ratio. The protective effect of glucose was partially reversed by either PPP or glycolysis inhibition. Conclusions. Glucose rescued cultured rat retinal cells from rotenone-induced toxicity. Glucose acted via both the PPP and the glycolytic pathway, maintaining cellular ATP and NAD(P)H levels and reducing ROS production. These data have implications for treatment of retinal diseases that involve metabolic compromise to neurons.
Keywords: rotenone; glucose; neuroprotection; experimental anoxia; glycolysis; pentose phosphate pathway
Rights: Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc.
RMID: 0020133508
DOI: 10.1167/iovs.13-12200
Grant ID: http://purl.org/au-research/grants/nhmrc/626964
Appears in Collections:Opthalmology & Visual Sciences publications

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